dka as first presentation of diabetes

DYANNE P. WESTERBERG, DO

This is a corrected version of the article that appeared in print.

Am Fam Physician. 2013;87(5):337-346

Patient Information: A handout on this topic is available at https://familydoctor.org/familydoctor/en/diseases-conditions/diabetic-ketoacidosis.html .

Author disclosure: No relevant financial affiliations.

Diabetic ketoacidosis is characterized by a serum glucose level greater than 250 mg per dL, a pH less than 7.3, a serum bicarbonate level less than 18 mEq per L, an elevated serum ketone level, and dehydration. Insulin deficiency is the main precipitating factor. Diabetic ketoacidosis can occur in persons of all ages, with 14 percent of cases occurring in persons older than 70 years, 23 percent in persons 51 to 70 years of age, 27 percent in persons 30 to 50 years of age, and 36 percent in persons younger than 30 years. The case fatality rate is 1 to 5 percent. About one-third of all cases are in persons without a history of diabetes mellitus. Common symptoms include polyuria with polydipsia (98 percent), weight loss (81 percent), fatigue (62 percent), dyspnea (57 percent), vomiting (46 percent), preceding febrile illness (40 percent), abdominal pain (32 percent), and polyphagia (23 percent). Measurement of A1C, blood urea nitrogen, creatinine, serum glucose, electrolytes, pH, and serum ketones; complete blood count; urinalysis; electrocardiography; and calculation of anion gap and osmolar gap can differentiate diabetic ketoacidosis from hyperosmolar hyperglycemic state, gastroenteritis, starvation ketosis, and other metabolic syndromes, and can assist in diagnosing comorbid conditions. Appropriate treatment includes administering intravenous fluids and insulin, and monitoring glucose and electrolyte levels. Cerebral edema is a rare but severe complication that occurs predominantly in children. Physicians should recognize the signs of diabetic ketoacidosis for prompt diagnosis, and identify early symptoms to prevent it. Patient education should include information on how to adjust insulin during times of illness and how to monitor glucose and ketone levels, as well as information on the importance of medication compliance.

Diabetic ketoacidosis (DKA) continues to have high rates of morbidity and mortality despite advances in the treatment of diabetes mellitus. In a study of 4,807 episodes of DKA, 14 percent occurred in persons older than 70 years, 23 percent in persons 51 to 70 years of age, 27 percent in persons 30 to 50 years of age, and 36 percent in persons younger than 30 years. 1 In a second study of 28,770 persons younger than 20 years (mean age of 14 years) with diabetes, 94 percent had no episodes of DKA, 5 percent had one episode, and 1 percent had at least two episodes. 2 Additionally, DKA occurred more often in females, in persons with a migration background, and in persons 11 to 15 years of age. 2 DKA has a case fatality rate of 1 to 5 percent. 3 , 4 Although the highest rate of mortality is in older adults and persons with comorbid conditions, DKA is the leading cause of death in persons younger than 24 years with diabetes, most often because of cerebral edema. 1 , 4

Although persons with DKA typically have a history of diabetes, 27 to 37 percent have newly diagnosed diabetes. 5 , 6 This is especially true in young children. Most persons with DKA have type 1 diabetes. There is also a subgroup of persons with type 2 diabetes who have ketosis-prone diabetes; this subgroup represents 20 to 50 percent of persons with DKA. 7 Persons with ketosis-prone diabetes have impaired insulin secretion; however, with proper glucose management, beta cell function improves and the clinical course resembles that of type 2 diabetes. 8 These persons are often black or Latino, male, middle-aged, overweight or obese, have a family history of diabetes, and have newly diagnosed diabetes. 9

Pathophysiology

DKA results from insulin deficiency from new-onset diabetes, insulin noncompliance, prescription or illicit drug use, and increased insulin need because of infection ( Table 1 ) . 4 , 10 – 16 This insulin deficiency stimulates the elevation of the counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). Without the ability to use glucose, the body needs alternative energy sources. Lipase activity increases, causing a breakdown of adipose tissue that yields free fatty acids. These components are converted to acetyl coenzyme A, some of which enter the Krebs cycle for energy production; the remainder are broken down into ketones (acetone, acetoacetate, and β-hydroxybutyrate). Ketones can be used for energy, but accumulate rapidly. Glycogen and proteins are catabolized to form glucose. Together, these factors promote hyperglycemia, which leads to an osmotic diuresis resulting in dehydration, metabolic acidosis, and a hyperosmolar state ( eFigure A ) .

TYPICAL CLINICAL PRESENTATION

The presentation of DKA varies with severity and comorbid conditions. Polyuria with polydipsia is the most common presenting symptom and was found in 98 percent of persons in one study of childhood type 1 diabetes. Other common symptoms included weight loss (81 percent), fatigue (62 percent), dyspnea (57 percent), vomiting (46 percent), preceding febrile illness (40 percent), abdominal pain (32 percent), and polyphagia (23 percent). 17 Dehydration causes tachycardia, poor skin turgor, dry mucous membranes, and orthostatic hypotension. The metabolic acidosis may lead to compensatory deep (Kussmaul) respirations, whereas increased acetone can be sensed as a fruity smell on the patient's breath. Mental status can vary from somnolence to lethargy and coma. A detailed evaluation may reveal precipitating factors, especially nonadherence to medical regimens and infection, which are common causes of DKA.

DIFFERENTIAL DIAGNOSIS

Although hyperosmolar hyperglycemic state can be confused with DKA, ketone levels are low or absent in persons with hyperosmolar hyperglycemic state. Other causes of high anion gap metabolic acidosis, such as alcoholic ketoacidosis and lactic acidosis, must be ruled out. Table 2 provides the differential diagnosis of DKA. 14 , 18

DIAGNOSTIC TESTING

The diagnosis of DKA ( Table 3 ) is based on an elevated serum glucose level (greater than 250 mg per dL [13.88 mmol per L]), an elevated serum ketone level, a pH less than 7.3, and a serum bicarbonate level less than 18 mEq per L (18 mmol per L). 4 Although arterial blood gas measurement remains the most widely recommended test for determining pH, measurement of venous blood gas has gained acceptance. One review indicated that venous and arterial pH are clinically interchangeable in persons who are hemodynamically stable and without respiratory failure. 19 Traditionally, the severity of DKA is determined by the arterial pH, bicarbonate level, anion gap, and mental status of the patient ( Table 3 ) . 4 An anion gap greater than 16 mEq per L (16 mmol per L) confirms metabolic acidosis. Although persons with DKA usually have a glucose level greater than 250 mg per dL, a few case reports document DKA in pregnant women who were euglycemic. 20 , 21 Persons with hyperglycemia have pseudohyponatremia, and serum sodium concentration should be corrected. Table 4 provides formulas to calculate the anion gap, serum osmolality, osmolar gap, and serum sodium correction. 16 [ corrected ]

Urinalysis measures only acetone and acetoacetate, not β-hydroxybutyrate, which is the primary ketone in DKA. In one study, the urine dipstick test was negative for ketones in six of 18 persons. Ketonemia was defined as a ketone level greater than 0.42 mmol per L. 22 In a second study of point-of-care testing in the emergency department, urine dipstick testing for ketones had a sensitivity of 98 percent, specificity of 35 percent, and a positive predictive value of 15 percent. Serum testing for β-hydroxybutyrate had a sensitivity of 98 percent, a specificity of 79 percent, and a positive predictive value of 34 percent (using a cutoff of greater than 1.5 mmol per L), allowing for more accurate diagnosis of DKA. 23 The American Diabetes Association has revised its position on ketone analysis in favor of serum testing, and has concluded that capillary measurement is equivalent to venous measurement. 4 , 22 , 24

Further initial laboratory studies should include measurement of electrolytes, phosphate, blood urea nitrogen, and creatinine; urinalysis; complete blood count with differential; and electrocardiography ( Table 5 ) . 16 Potassium level is normal or low in persons with DKA, despite renal losses caused by the acidic environment. An initial potassium level less than 3.3 mEq per L (3.3 mmol per L) indicates profound hypokalemia. Amylase and lipase levels may be increased in persons with DKA, even in those without associated pancreatitis; however, 10 to 15 percent of persons with DKA do have concomitant pancreatitis. 18 , 25

Leukocytosis can occur even in the absence of infection; bandemia more accurately predicts infection. One study showed that an elevated band count in persons with DKA had a sensitivity for predicting infection of 100 percent (19 out of 19 cases) and a specificity of 80 percent. 26 Chest radiography and urine and blood cultures should be added for further evaluation of infection. An elevated hemoglobin level caused by dehydration may also exist. Elevated hepatic transaminase levels may occur, especially in persons with fatty liver disease. 27 Mild increases in creatine kinase and troponin levels may occur in the absence of myocardial damage; one study demonstrated that increased troponin levels occurred in 26 out of 96 persons with DKA without a coronary event. 28 Finally, the A1C level indicates the degree of glycemic control in persons known to have diabetes.

Figure 1 4 , 29 provides the treatment approach for DKA in adults, and Figure 2 24 , 30 provides the treatment approach for DKA in persons younger than 20 years. Both approaches are recommended by the American Diabetes Association. Specific issues for the adult patient are discussed in more detail below. For persons younger than 20 years, insulin should be administered gradually, and fluid and electrolyte replacement should be done cautiously because of limited data and concern for precipitating cerebral edema.

FLUID REPLACEMENT

After determining the level of dehydration, intravenous fluid replacement should be started. In most persons, saline 0.9% is started at 15 to 20 mL per kg per hour, or 1 L per hour initially. Fluid status, cardiac status, urine output, blood pressure, and electrolyte level should be monitored. As the patient stabilizes, fluids can be lowered to 4 to 14 mL per kg per hour, or 250 to 500 mL per hour. Once the corrected sodium concentration is normal or high (greater than 135 mEq per L [135 mmol per L]), the solution can be changed to saline 0.45%. Dextrose is added when the glucose level decreases to 200 mg per dL (11.10 mmol per L). 4

To further correct hyperglycemia, insulin should be added to intravenous fluids one to two hours after fluids are initiated. An initial bolus of 0.1 units per kg should be given with an infusion of 0.1 units per kg per hour. 4 Some believe this bolus is unnecessary as long as an adequate infusion of insulin is maintained. 31 An infusion of 0.14 units per kg per hour is recommended in the absence of a bolus. Glucose level should decrease by about 50 to 70 mg per dL (2.77 to 3.89 mmol per L) per hour, and the insulin infusion should be adjusted to achieve this goal. 4 Once the glucose level decreases to 200 mg per dL, the insulin infusion rate should be decreased to 0.05 to 0.1 units per kg per hour, and dextrose should be added to the intravenous fluids to maintain a glucose level between 150 and 200 mg per dL (8.32 and 11.10 mmol per L). 4 Subcutaneous insulin is an effective alternative to intravenous insulin in persons with uncomplicated DKA. 29 In one prospective randomized trial of 45 persons, 15 received insulin aspart (Novolog) hourly, 15 received insulin aspart every two hours, and 15 received standard intravenous infusion of regular insulin. Physiologic and clinical outcomes were identical in all three groups. 32 A meta-analysis supports subcutaneous administration of rapid-acting insulin analogues, such as lispro (Humalog), every hour (bolus of 0.3 units per kg, then 0.1 units per kg) or two hours (bolus of 0.3 units per kg, then 0.2 units per kg) as a reasonable alternative to intravenous regular insulin for treating uncomplicated DKA. 29

DKA is resolved when the glucose level is less than 200 mg per dL, the pH is greater than 7.3, and the bicarbonate level is 18 mEq per L or higher. 4

Once these levels are achieved and oral fluids are tolerated, the patient can be started on an insulin regimen that includes an intermediate- or long-acting insulin and a short- or rapid-acting insulin. When intravenous insulin is used, it should remain in place for one to two hours after subcutaneous insulin is initiated. Persons known to have diabetes can be started on their outpatient dose, with adjustments to improve control. Those new to insulin should receive 0.5 to 0.8 mg per kg per day in divided doses. 4

Although potassium is profoundly depleted in persons with DKA, decreased insulin levels, acidosis, and volume depletion cause elevated extracellular concentrations. Potassium levels should be monitored every two to four hours in the early stages of DKA. Hydration alone will cause potassium to drop because of dilution. Improved renal perfusion will increase excretion. Insulin therapy and correction of acidosis will cause cellular uptake of potassium. If the potassium level is in the normal range, replacement can start at 10 to 15 mEq potassium per hour. During treatment of DKA, the goal is to maintain serum potassium levels between 4 and 5 mEq per L (4 and 5 mmol per L). If the potassium level is between 3.3 and 5.2 mEq per L (3.3 and 5.2 mmol per L) and urine output is normal, replacement can start at 20 to 30 mEq potassium per hour. If the potassium level is lower than 3.3 mEq per L, insulin should be held and replacement should be started at 20 to 30 mEq potassium per hour. If the potassium level is greater than 5.2 mEq per L, insulin therapy without potassium replacement should be initiated, and serum potassium levels should be checked every two hours. When the potassium level is between 3.3 and 5.2 mEq per L, potassium replacement should be initiated. 4 Some guidelines recommend potassium replacement with potassium chloride, whereas others recommend combining it with potassium phosphate or potassium acetate. Clinical trials are lacking to determine which is best, although in the face of phosphate depletion, potassium phosphate is used.

BICARBONATE

Bicarbonate therapy in persons with DKA is somewhat controversial. Proponents believe that severe acidosis will cause cardiac and neurologic complications. However, studies have not demonstrated improved clinical outcomes with bicarbonate therapy, and treatment has been associated with hypokalemia. In one retrospective quasi-experimental study of 39 persons with DKA and a pH between 6.9 and 7.1, there was no difference in outcomes between those who received bicarbonate therapy and those who did not. 33 A second study of 106 adolescents with DKA showed no difference in outcomes in patients treated with and without sodium bicarbonate, but few had a pH below 7 and only one had a pH below 6.9. 34

Current American Diabetes Association guidelines continue to recommend bicarbonate replacement in persons with a pH lower than 6.9 using 100 mEq of sodium bicarbonate in 400 mL of sterile water with 20 mEq of potassium chloride at a rate of 200 mL per hour for two hours. This should be repeated every two hours until the patient's pH is 6.9 or greater. 4

PHOSPHATE AND MAGNESIUM

Phosphate levels may be normal to elevated on presentation, but decline with treatment as the phosphate enters the intracellular space. Studies have not shown a benefit from phosphate replacement, and it can be associated with hypocalcemia and hypomagnesemia. However, because phosphate deficiency is linked with muscle fatigue, rhabdomyolysis, hemolysis, respiratory failure, and cardiac arrhythmia, replacement is recommended when the phosphate level falls below 1.0 mg per dL (0.32 mmol per L) or when these complications occur. 4 Persons with anemia or respiratory problems and congestive heart failure may benefit from phosphate. This can be achieved by adding 20 to 30 mEq of potassium phosphate to the intravenous fluid. 4

DKA can cause a drop in magnesium, which can result in paresthesia, tremor, muscle spasm, seizures, and cardiac arrhythmia. It should be replaced if it falls below 1.2 mg per dL or if symptoms of hypomagnesemia develop. 35

Complications

Cerebral edema is the most severe complication of DKA. It occurs in 0.5 to 1 percent of all DKA cases, 36 , 37 and carries a mortality rate of 21 to 24 percent. 30 Survivors are at risk of residual neurologic problems. 38 Cerebral edema predominantly occurs in children, although it has been reported in adults. 39 Risk factors include younger age, new-onset diabetes, longer duration of symptoms, lower partial pressure of carbon dioxide, severe acidosis, low initial bicarbonate level, low sodium level, high glucose level at presentation, rapid hydration, and retained fluid in the stomach. 30 , 40 Signs of cerebral edema that require immediate evaluation include headache, persistent vomiting, hypertension, bradycardia, and lethargy and other neurologic changes.

Other complications of DKA include hypokalemia, hypoglycemia, acute renal failure, and shock. Less common problems can include rhabdomyolysis, 41 thrombosis and stroke, 42 pneumomediastinum, 43 prolonged corrected QT interval, 44 pulmonary edema, 45 and memory loss with decreased cognitive function in children. 46

Physicians should recognize signs of diabetes in all age groups, and should educate patients and caregivers on how to recognize them as well ( eTable A ) . In one study, persons with DKA had symptoms of diabetes for 24.5 days before developing DKA. 17 Persons with diabetes and their caregivers should be familiar with adjusting insulin during times of illness. This includes more frequent glucose monitoring; continuing insulin, but at lower doses, during times of decreased food intake; and checking urine ketone levels with a dipstick test if the glucose level is greater than 240 mg per dL (13.32 mmol per L). 47 More accessible home measurement of serum ketones with a commercial glucometer may allow for earlier detection of DKA and decreased hospital visits. 48 Persons with an insulin pump need to know their pump settings, and should maintain a prescription for basal insulin in case of pump failure.

Nonadherence to medical regimens is often the cause of recurrent DKA. Physicians need to recognize patient barriers to getting care, such as financial, social, psychological, and cultural reasons. Diabetes education with certified educators and pharmacists enhances patient care. 49 , 50 Other prevention techniques include group visits, telecommunication, web-based learning, and copay reduction for diabetes medications; however, evidence for their effectiveness is mixed. 51 – 55

Data Sources: In July 2010, an initially broad search of PubMed, Essential Evidence Plus, and sources such as the Cochrane database and Clinical Evidence was conducted using the key term diabetic ketoacidosis. In the fall of 2010, another search was conducted using additional key terms, such as incidence and prevalence. As information was collected, individual questions were then searched to add finer points to the documentation. The searches were repeated with each draft of the manuscript.

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Diabetic ketoacidosis

On this page, when to see a doctor, risk factors, complications.

Diabetic ketoacidosis is a serious complication of diabetes.

The condition develops when the body can't produce enough insulin. Insulin plays a key role in helping sugar — a major source of energy for muscles and other tissues — enter cells in the body.

Without enough insulin, the body begins to break down fat as fuel. This causes a buildup of acids in the bloodstream called ketones. If it's left untreated, the buildup can lead to diabetic ketoacidosis.

If you have diabetes or you're at risk of diabetes, learn the warning signs of diabetic ketoacidosis and when to seek emergency care.

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Diabetic ketoacidosis symptoms often come on quickly, sometimes within 24 hours. For some, these symptoms may be the first sign of having diabetes. Symptoms might include:

• Being very thirsty
• Urinating often
• Feeling a need to throw up and throwing up
• Having stomach pain
• Being weak or tired
• Being short of breath
• Having fruity-scented breath
• Being confused

More-certain signs of diabetic ketoacidosis — which can show up in home blood and urine test kits — include:

• High blood sugar level
• High ketone levels in urine

If you feel ill or stressed or you've had a recent illness or injury, check your blood sugar level often. You might also try a urine ketone test kit you can get at a drugstore.

Contact your health care provider right away if:

• You're throwing up and can't keep down food or liquid
• Your blood sugar level is higher than your target range and doesn't respond to home treatment
• Your urine ketone level is moderate or high

Seek emergency care if:

• Your blood sugar level is higher than 300 milligrams per deciliter (mg/dL), or 16.7 millimoles per liter (mmol/L) for more than one test.
• You have ketones in your urine and can't reach your health care provider for advice.
• You have many symptoms of diabetic ketoacidosis. These include excessive thirst, frequent urination, nausea and vomiting, stomach pain, weakness or fatigue, shortness of breath, fruity-scented breath, and confusion.

Remember, untreated diabetic ketoacidosis can lead to death.

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Sugar is a main source of energy for the cells that make up muscles and other tissues. Insulin helps sugar enter the cells in the body.

Without enough insulin, the body can't use sugar to make the energy it needs. This causes the release of hormones that break down fat for the body to use as fuel. This also produces acids known as ketones. Ketones build up in the blood and eventually spill over into the urine.

Diabetic ketoacidosis usually happens after:

• An illness. An infection or other illness can cause the body to make higher levels of certain hormones, such as adrenaline or cortisol. These hormones work against the effects of insulin and sometimes cause diabetic ketoacidosis. Pneumonia and urinary tract infections are common illnesses that can lead to diabetic ketoacidosis.
• A problem with insulin therapy. Missed insulin treatments can leave too little insulin in the body. Not enough insulin therapy or an insulin pump that doesn't work right also can leave too little insulin in the body. Any of these problems can lead to diabetic ketoacidosis.

Other things that can lead to diabetic ketoacidosis include:

• Physical or emotional trauma
• Heart attack or stroke
• Pancreatitis
• Alcohol or drug misuse, particularly cocaine
• Certain medicines, such as corticosteroids and some diuretics

The risk of diabetic ketoacidosis is highest if you:

• Have type 1 diabetes
• Often miss insulin doses

Sometimes, diabetic ketoacidosis can occur with type 2 diabetes. In some cases, diabetic ketoacidosis may be the first sign of having diabetes.

Diabetic ketoacidosis is treated with fluids, electrolytes — such as sodium, potassium and chloride — and insulin. Perhaps surprisingly, the most common complications of diabetic ketoacidosis are related to this lifesaving treatment.

Possible complications of the treatments

Treatment complications include:

• Low blood sugar, also known as hypoglycemia. Insulin allows sugar to enter cells. This causes the blood sugar level to drop. If the blood sugar level drops too quickly, the drop can lead to low blood sugar.
• Low potassium, also known as hypokalemia. The fluids and insulin used to treat diabetic ketoacidosis can cause the potassium level to drop too low. A low potassium level can affect the heart, muscles and nerves. To avoid this, potassium and other minerals are usually given with fluid replacement as part of the treatment of diabetic ketoacidosis.
• Swelling in the brain, also known as cerebral edema. Adjusting the blood sugar level too quickly can cause the brain to swell. This appears to be more common in children, especially those with newly diagnosed diabetes.

Untreated, diabetic ketoacidosis can lead to loss of consciousness and, eventually, death.

There are many ways to prevent diabetic ketoacidosis and other diabetes complications.

• Manage your diabetes. Make healthy eating and physical activity part of your daily routine. Take diabetes medicines or insulin as directed.
• Monitor your blood sugar level. You might need to check and record your blood sugar level at least 3 to 4 times a day, or more often if you're ill or stressed. Careful monitoring is the only way to make sure that your blood sugar level stays within your target range.
• Adjust your insulin dosage as needed. Talk to your health care provider or diabetes educator about how to make your insulin dosage work for you. Consider factors such as your blood sugar level, what you eat, how active you are, and whether you're ill. If your blood sugar level begins to rise, follow your diabetes treatment plan to return your blood sugar level to your target range.
• Check your ketone level. When you're ill or stressed, test your urine for excess ketones with a urine ketones test kit. You can buy test kits at a drugstore. If your ketone level is moderate or high, contact your health care provider right away or seek emergency care. If you have low levels of ketones, you may need to take more insulin.
• Be prepared to act quickly. If you think you have diabetic ketoacidosis because your blood sugar is high and you have too many ketones in your urine, seek emergency care.

Diabetes complications are scary. But don't let fear keep you from taking good care of yourself. Follow your diabetes treatment plan carefully. Ask your diabetes treatment team for help when you need it.

Oct 06, 2022

• DKA (ketoacidosis) and ketones. American Diabetes Association. https://diabetes.org/diabetes/dka-ketoacidosis-ketones. Accessed Sept. 17, 2022.
• Diabetic ketoacidosis (DKA). Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/diabetic-ketoacidosis-dka?query=Diabetic ketoacidosis (DKA). Accessed Sept. 17, 2022.
• Hirsch IB, et al. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis. https://www.uptodate.com/contents/search. Accessed Sept. 17, 2022.
• Hirsch IB, et al. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment. https://www.uptodate.com/contents/search. Accessed Sept. 17, 2022.
• Ferri FF. Diabetic ketoacidosis. In: Ferri's Clinical Advisor 2023. Elsevier; 2023. https://www.clinicalkey.com. Accessed Sept. 17, 2022.
• Evans K. Diabetic ketoacidosis: Update on management. Clinical Medicine. 2019; doi:10.7861/clinmed.2019-0284.
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Diabetic ketoacidosis in adults

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This article has a correction. Please see:

• Diabetic ketoacidosis in adults - November 02, 2015
• Shivani Misra , clinical research fellow and specialist trainee year 6 in metabolic medicine 1 2 ,
• Nick S Oliver , consulant diabetologist and reader in diabetes 1 3
• 1 Department of Diabetes, Endocrinology & Metabolism, Imperial College, London W2 1PG, UK
• 2 Clinical Biochemistry & Metabolic Medicine, Imperial Healthcare NHS Trust, London, UK
• 3 Diabetes and Endocrinology, Imperial Healthcare NHS Trust, London, UK
• Correspondence to: N S Oliver nick.oliver{at}imperial.ac.uk

What you should know

Diabetic ketoacidosis (DKA) is a common, serious, and preventable complication of type 1 diabetes, with a mortality of 3-5%. It can also occur in patients with other types of diabetes

It can be the first presentation of diabetes. This accounts for about 6% of cases

The diagnosis is not always apparent and should be considered in anyone with diabetes who is unwell

Diagnosis is based on biochemical criteria. However, hyperglycaemia may not always be present and low blood ketone levels (<3 mmol/L) do not always exclude DKA

Immediate treatment consists of intravenous fluids, insulin, and potassium, with careful monitoring of blood glucose and potassium levels to avoid hypoglycaemia and hypokalaemia

Knowledge of the type of diabetes at the time of DKA does not affect immediate treatment, and all patients with DKA should be advised to continue with insulin on discharge

Subsequent management should focus on patient education and support to avoid recurrence

Patients should be managed by a specialist multidisciplinary team during and after an episode of DKA

What is DKA?

Diabetic ketoacidosis (DKA) is an extreme metabolic state caused by insulin deficiency. The breakdown of fatty acids (lipolysis) produces ketone bodies (ketogenesis), which are acidic. Acidosis occurs when ketone levels exceed the body’s buffering capacity (figure ⇓ ). 1 2

Diabetic ketoacidosis may follow absolute insulin deficiency or relative insulin deficiency. Relative insulin deficiency may occur in the presence of increased levels of counter-regulatory hormones such as glucagon, cortisol, and catecholamines. Insulin deficiency results in lipolysis and ketogenesis. Ketone bodies are acidic and may initially be buffered, but when levels are high enough, will result in acidosis

How common is DKA?

Data from the UK National Diabetes audit shows a crude one year incidence of 3.6% among people with type 1 diabetes. 3 In the UK nearly 4% of people with type 1 diabetes experience DKA …

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In this section

Diabetic Ketoacidosis

This guideline has been adapted for statewide use with the support of the Victorian Paediatric Clinical Network

See also:      .

Diabetes mellitus   Diabetes phone calls  

Diabetes mellitus and surgery           

• Cerebral oedema is the key life-threatening complication of DKA
• When managing DKA, hypoglycaemia and hypo/hyperkalaemia are the other main complications which must be monitored for and treated
• Children with DKA are deplete in total body potassium regardless of the initial serum potassium level
• Measured serum sodium may be low due to osmotic dilution with glucose.  Corrected sodium levels should be calculated and monitored 

The biochemical criteria for diagnosis of DKA are:

• Serum glucose >11 mmol/L
• Venous pH <7.3 or Bicarbonate <15 mmol/L
• Presence of ketonaemia/ketonuria

Children with hyperglycaemia (Blood glucose level (BGL) >11 mmol/L) +/- ketosis who are not acidotic can be managed with subcutaneous insulin (see Diabetes mellitus , new presentation, mildly ill).

Hyperglycaemic children with altered conscious state who are not acidotic (pH of ≥7.3) and have little to no ketonaemia may have hyperglycaemic-hyperosmolar non-ketotic coma.   If this is a possibility, insulin should ONLY be given after discussion with local paediatric team and/or paediatric endocrinologist. 

Precipitants for DKA

• Inadequate insulin in a child or adolescent with known diabetes (eg missed insulin doses, insulin pump failure).
• First presentation of Type 1 diabetes mellitus.

History and examination are directed towards potential precipitants, assessment of severity, and detecting complications of DKA.

Assessment of Dehydration

Weigh child – compare to recent weight if available.

• The degree of dehydration is often over-estimated in DKA, this may be compounded by peripheral shutdown due to acidosis.
• Excessive fluid replacement may increase the risk of cerebral oedema.

Children and adolescents with DKA should be managed in a unit that has:

• Access to laboratory services for frequent and timely evaluation of biochemical variables
• Experienced nursing staff trained in monitoring and management of DKA in children and adolescents
• A paediatrician, endocrinologist, or critical care specialist with training and expertise in the management of paediatric DKA. Where such expertise is not available on-site, telephone advice should be sought from the appropriate specialists

Investigations

Bloods - Insert an IV when taking bloods

• Serum glucose
• Urea, creatinine and electrolytes (sodium, potassium, calcium, magnesium, phosphate)
• Venous gas (including bicarbonate)
• FBE (haematocrit may be elevated as a marker of dehydration, WCC may be elevated as a stress response)
• Blood ketones (bedside test, normal <0.6 mmol/L)
• Consider investigations for precipitating cause: if clinical signs of infection consider septic work up
• The following bloods are part of a diagnostic work up for first presentation T1DM: Insulin antibodies, GAD antibodies, ZnT8 antibodies, celiac screen (total IgA, anti-gliadin Ab, tissue transglutaminase Ab) TSH and fT4.  Collect these bloods with initial blood sampling if practical.  Please handover to admitting team if not done
• Dipstick for ketones, glucose and FWT
• Culture if clinical suspicion of UTI

Consider ECG if potassium results will be delayed 

Once DKA is confirmed, the following biochemical monitoring should be put in place to guide ongoing management.  These will continue until resolution of DKA:

• Hourly – BGL, bedside ketone testing
• At 2 hours and 2-4 hourly thereafter – VBG, UEC, Ca, Mg, PO4

Severity of DKA

Goals of Treatment:

Sections below include:

• Correct dehydration
• Reverse ketosis, correct acidosis and glucose
• Monitor for complications of DKA and its treatment: Cerebral oedema, hypo/hyperkalaemia, hypoglycaemia
• Identify and treat any precipitating cause   

Airway/Breathing/Circulation

            See Resuscitation

Supportive measures and monitoring

• Nurse head up
• In children with reduced conscious state monitor airway safety.  Consider inserting an NGT to prevent aspiration
• Keep nil by mouth until child is alert and preferably until acidosis resolves.  Children can be given ice to suck on for comfort
• Insert second IVC to use as a blood sampling line, take initial diagnostic bloods if not drawn with initial IVC insertion
• Supplemental oxygen for children with severe circulatory impairment or shock
• Cardiac monitoring – for assessment of ECG changes related to potassium levels (hyperkalaemia: peaked T waves, widened QRS, hypokalaemia: flattened or inverted T waves, ST depression, PR prolongation). See ECG Interpretation
• Consider antibiotics for febrile children after obtaining appropriate cultures
• Consider urinary catheter for children who are unconscious to allow strict monitoring of fluid balance.  Weighing nappies can be used for strict fluid balance for children who can’t urinate on demand

Timeline of monitoring and management

1) Correct Dehydration

Children with DKA will be dehydrated.  Clinical estimates of fluid deficits are subjective and often inaccurate thus most children can initially be commenced on the “mild” or “moderate” fluid rate (see below).

A 10 mL/kg 0.9% sodium chloride bolus can be given to children who are tachycardic with delayed central capillary refill. 

• This should be followed by a reassessment  
• Acidosis results in poor peripheral perfusion so use central capillary refill with vital signs to assess response to fluids  

Initial Fluid Replacement

Commence rehydration with isotonic fluid eg 0.9% sodium chloride. 

• Ask child to pass urine or remove nappy
• Add 40 mmol/L potassium chloride to this fluid if the serum potassium ≤ 5.5mmol/L and the child is passing urine  
• If anuric or serum potassium >5.5 mmol/L, do not add potassium to the fluids until this has resolved

Keep nil by mouth until child is alert and acidosis has resolved. 

• Children can be given ice to suck on for comfort.

Intravenous or oral fluids that have been given at another facility may need to be factored into the assessment and calculation of fluid deficit and replacement. 

• If the child has received more than 20 mL/kg, discuss the adjustment of fluids with the consultant.

Initial fluid rates (mL/hr) based on degree of dehydration

  Fluid Adjustments

Frequent monitoring of electrolytes, glucose, and osmolality will guide fluid composition and infusion rates.  Fluids containing 0.9% sodium chloride should be continued for at least the first 6 hours. 

The three key parameters to monitor and manage are:

Osmolality can be calculated using the following formula:

Osmolality = 2 x (serum sodium + serum potassium) + glucose + urea

• BGL will decrease rapidly during initial rehydration / volume expansion and continue to decrease once the insulin infusion is started
• Once BGL is ≤ 15 mmol/L change fluids to 0.9% sodium chloride with 5% glucose and potassium chloride (maximum 60 mmol/L) as required
• Aim to keep the BGL between 5-10 mmol/L
• If BGL falls below 5mmol/L or is falling rapidly (>5 mmol/L/hour) in the range between 5-15 mmol/L and the child remains acidotic, increase the glucose content to 10%
• Insulin infusion rate should only be decreased if BGL continues to fall despite glucose concentration of 10%
• Children with DKA have a deficit of total body potassium however serum potassium levels may be normal, high, or low
• Treatment with insulin will shift potassium to the intracellular space rapidly resulting in hypokalaemia if potassium is not replaced
• Start potassium chloride at a concentration of 40 mmol/L, increase to a maximum 60 mmol/L if required to maintain serum potassium in the normal range
• Once insulin is commenced, a repeat serum potassium should be measured within one hour and two to four hourly thereafter

Measured sodium is depressed by the dilutional effect of hyperglycaemia

• 0.9% sodium chloride with glucose and potassium chloride (maximum 60 mmol/L) as required should generally be used for the duration of IV rehydration 
• If a hypotonic solution is later thought to be required, discuss this with the paediatric endocrinologist on call.  The sodium chloride content should be at least 0.45% or greater
• If measured sodium does not rise as the glucose falls during treatment or if hyponatraemia develops, this usually indicates excessive fluid correction which may increase the risk of cerebral oedema
• Extremes of corrected sodium should be discussed with a senior doctor early

IV fluids can be ceased once pH and bicarbonate have normalised and the child is able to tolerate oral intake (this usually coincides with insulin being changed to subcutaneous injections).

• Phosphate replacement is rarely required (due to intracellular phosphate stores usually being adequate)
• If phosphate levels drop below 0.32 mmol/L and/or symptoms of hypophosphataemia are present, IV phosphate replacement may be required
• Calcium levels will need to be monitored if IV phosphate is administered

2) Reverse ketosis and correct acidosis

IV rehydration should be commenced prior to starting an insulin infusion.

To make up the insulin infusion:

• Add 50 units of clear/rapid acting insulin (Actrapid HM or Humulin R) to 49.5 mL of 0.9% sodium chloride to form a 1 unit/mL solution.

Initial insulin infusion rates

• Children with DKA should generally be commenced at 0.1 units/kg/hour 
• Children undergoing inter-hospital transfer (limited access to biochemical monitoring)
• Children less than 5 years old
• Children with BGL <15 mmol/L at the time of commencement of the insulin infusion

Practical points

• Insulin infusion can be run as a sideline with the rehydration fluids via a three-way tap provided a syringe pump is used.  Ensure the insulin is clearly labelled
• Adequate insulin must be continued to clear ketones and correct acidosis  
• Aim to keep the blood glucose between 5-10 mmol/L by increasing the fluid glucose concentration to 10% before adjusting the insulin infusion rate
• Can be changed when child is alert and metabolically stable (pH>7.3, HCO3 > 15)
• Best time to change to subcutaneous insulin is just prior to a meal. Discuss the dose and regimen with the consultant on call
• Continue the insulin infusion for 30 minutes after the first subcutaneous injection of rapid-acting insulin, then cease

3) Monitor for complications of DKA and its treatment

The most important complications of DKA and its treatment are:

• Cerebral oedema

Hypoglycaemia

• Hypo/hyperkalaemia
• Hypo/hypernatraemia
• Aspiration (if obtunded)

Cerebral Oedema

• Some degree of subclinical brain swelling is present during most episodes of DKA
• Clinical cerebral oedema occurs suddenly, usually between 6-12 hours after starting therapy (range 2-24 hours)
• Mortality and severe morbidity rates are very high without early treatment
• If cerebral oedema is suspected, this should be immediately discussed with a consultant

Risk Factors

• First presentation diabetes
• Long history of poor control
• Age <5 years old
• Early: Headache, irritability, lethargy, vomiting
• Later: depressed consciousness, incontinence, thermal instability
• Very late: bradycardia, increased BP, respiratory impairment
• Reduce fluid infusion rate by one-third
• Contact Paediatric, Infant and Perinatal Emergency Retrievals on 1300 137 650[KH14] 
• Give mannitol immediately if cerebral oedema suspected – do NOT wait for cerebral imaging.
• Mannitol 20% (0.2 g/mL) dose: 0.5 g/kg IV over 20 minutes (dose range: 0.25-1 g/kg), repeat if no improvement within 30-60mins.
• Discuss with consultant on call and liaise with intensive care or paediatric retrieval service to discuss transfer.

A BGL of <4.0 mmol/L should be treated with additional glucose as below.

• 2 mL/kg 10% glucose IV bolus (repeat if required) and change rehydration fluids to include 10% glucose with 0.9% sodium chloride, with potassium chloride (maximum 60 mmol/L) as required
• Do NOT discontinue the insulin infusion
• If hypoglycaemia occurs despite use of 10% glucose in preceding 2 hours – decrease insulin infusion to 0.05 units/kg/hr (0.03 units/kg/hr if previously on 0.05 units/kg/hr)
• Continue with 10% glucose in fluids until BGL is stable between 5-10 mmol/L
• Oral treatment for hypoglycaemia can be used if pH≥7.3 and the child is alert and able to tolerate oral intake. Use 4-5 Jelly beans or a serve of juice: 60 mL (5g carbohydrate) for children <25kg, 120 mL (10g carbohydrate) for children ≥25kg
• Recheck BGL after 15-20mins and give another serve of juice or jelly beans if BGL still <4.0 mmol/L.  If oral treatment has been used discuss timing of transition to sub-cutaneous insulin and oral diet with endocrinology / consultant on call

4) Identify and Treat precipitating cause

Assess for underlying infections and consider antibiotics after obtaining relevant cultures if appropriate. 

• Overall, infective precipitants are uncommon. 

In children with known T1DM the most common cause of DKA is omission or significant reduction in recent insulin doses.  

Other Things to Consider

Persisting acidosis.

If the acidosis is not correcting, consider the following:

• Insufficient insulin to switch off ketosis (check insulin delivery)
• Inadequate rehydration
• Hyperchloraemic acidosis (secondary to IV fluids)
• Salicylates or other substances that cause metabolic acidosis

Rarely required

Bicarbonate

• Discuss with consultant endocrinologist prior to administration
• ONLY appropriate for children with life threatening hyperkalaemia or requiring inotropic support
• May cause paradoxical CNS acidosis
• Associated with increased risk of cerebral oedema
• Administer IV over 30-60 minutes with cardiac monitoring
• Reassess acid-base status and beware of hypokalaemia

Consider consultation with local paediatric team for

All children with DKA All newly diagnosed diabetes mellitus Hyper/hyponatraemia

Consider transfer when

Intensive care monitoring is recommended for

• Children <2 years of age
• Cardiovascular compromise
• Signs of cerebral oedema
• Severe acidosis (pH <7.1 or HCO3<5)

The care required is beyond the level of comfort or resources of the local hospital.  Children and adolescents with DKA should be managed in a unit that has:

For emergency advice and paediatric or neonatal ICU transfers, call the Paediatric Infant Perinatal Emergency Retrieval (PIPER) Service: 1300 137 650.

Last Updated November 2018

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• Published: 14 May 2020

Diabetic ketoacidosis

• Ketan K. Dhatariya 1 , 2 ,
• Nicole S. Glaser 3 ,
• Ethel Codner 4 &
• Guillermo E. Umpierrez 5  

Nature Reviews Disease Primers volume  6 , Article number:  40 ( 2020 ) Cite this article

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• Diabetes complications
• Endocrine system and metabolic diseases
• Glycobiology

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present — ‘D’, either elevated blood glucose levels or a family history of diabetes mellitus; ‘K’, the presence of high urinary or blood ketoacids; and ‘A’, a high anion gap metabolic acidosis. Early diagnosis and management are paramount to improve patient outcomes. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with appreciable, although largely preventable, morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA and provide practical recommendations for the management of DKA in adults and children.

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Ketan K. Dhatariya

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Nicole S. Glaser

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Introduction (G.E.U., N.S.G., K.K.D., E.C.); Epidemiology (G.E.U., N.S.G., K.K.D., E.C.); Mechanisms/pathophysiology (G.E.U., N.S.G., K.K.D., E.C.); Diagnosis, screening and prevention (G.E.U., N.S.G., K.K.D., E.C.); Management (G.E.U., N.S.G., K.K.D., E.C.); Quality of life (N.S.G.); Outlook (N.S.G, E.C.); Overview of Primer (G.E.U.). All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published.

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K.K.D. is an employee of the UK National Health Service. N.S.G. has grants from American Diabetes Association (ADA, 1-17-IBS-186) and from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, U34DK123894). E.C. is partly funded by Fondo Nacional de Ciencia y Tecnología (FONDECYT) grant no. 1170895 from the Government of Chile. G.E.U. is partly supported by research grants from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under Award Number UL1TR002378 from the Clinical and Translational Science Award program and an NIH grant U30, P30DK11102, and has received research grant support to Emory University for investigator-initiated studies from Dexcom, Novo Nordisk and Sanofi.

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A reduction in intravascular and/or extracellular fluid volume, such that there may be an inability to adequately perfuse tissue.

Also known as the BMI standard deviation score. The z-score is a measure of a child’s relative weight adjusted for age and gender.

The negative base-10 logarithm of the acid dissociation constant (Ka) of a solution. The lower the pKa, the stronger the acid.

The ability of molecules in the circulation to stabilize the acid–base balance in an attempt to maintain the pH.

An estimate of how much blood passes through the renal glomeruli every minute, which is often calculated from serum creatinine levels, age, sex and body weight.

The loss of kidney function as a result of poor renal or glomerular perfusion, for example, due to haemorrhage, cardiac failure or hypovolaemia.

A state in which the circulating extracellular fluid has a higher osmotic pressure than the pressure that would be observed in a healthy individual.

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Dhatariya, K.K., Glaser, N.S., Codner, E. et al. Diabetic ketoacidosis. Nat Rev Dis Primers 6 , 40 (2020). https://doi.org/10.1038/s41572-020-0165-1

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About Diabetic Ketoacidosis

• Diabetic ketoacidosis (DKA) is serious and can be life-threatening.
• DKA develops when your body doesn’t have enough insulin to allow blood sugar into your cells for use as energy.
• DKA is most common among people with type 1 diabetes.

DKA is a serious complication of diabetes that can be life-threatening. DKA is most common among people with type 1 diabetes . People with type 2 diabetes can also develop DKA.

DKA develops when your body doesn't have enough insulin to allow blood sugar into your cells for use as energy. Instead, your liver breaks down fat for fuel, a process that produces acids called ketones. When too many ketones are produced too fast, they can build up to dangerous levels in your body.

Read on to learn more about DKA, how you can prevent DKA, and how to treat it if needed.

Signs and symptoms

DKA usually develops slowly. Early symptoms include:

• Being very thirsty.
• Urinating a lot more than usual.

If untreated, more severe symptoms can appear quickly, such as:

• Fast, deep breathing.
• Dry skin and mouth.
• Flushed face.
• Fruity-smelling breath.
• Muscle stiffness or aches.
• Being very tired.
• Nausea and vomiting.
• Stomach pain.

Sometimes DKA is the first sign of diabetes in people who haven't yet been diagnosed.

Very high blood sugar and low insulin levels lead to DKA. The two most common causes are:

• Illness. You may not be able to eat or drink as much as usual, which can make blood sugar hard to manage.
• Missing insulin shots, a clogged insulin pump, or the wrong insulin dose.

Other causes of DKA include:

• Heart attack or stroke.
• Physical injury, such as from a car accident.
• Alcohol or drug use.
• Certain medicines, such as some diuretics (water pills) and corticosteroids (used to treat inflammation in the body).

DKA is a serious condition, but you can take steps to help prevent it:

• Check your blood sugar often, especially if you're sick.
• Keep your blood sugar levels in your target range as much as possible.
• Take medicines as prescribed, even if you feel fine.
• Talk to your doctor about how to adjust your insulin based on what you eat, how active you are, or if you're sick.

If you're concerned about DKA or have questions about how to manage your diabetes , talk to your diabetes care team. Ask them for a referral to diabetes self-management education and support (DSMES) for individual guidance. DSMES services are a vital tool to help you manage and live well with diabetes while protecting your health.

Test for ketones

Anytime you're sick or your blood sugar is 240 mg/dL or above, you'll need to test for ketones. Use an over-the-counter ketone test kit to check your urine or a meter to test your blood every 4 to 6 hours. You should also test for ketones if you have any of the symptoms of DKA. Call your doctor if your ketones are moderate or high. Elevated ketones are a sign of DKA. This is a medical emergency that needs to be treated immediately .

Go to the emergency room or call 911 right away if you can't get in touch with your doctor and if you're having any of these signs:

• Your blood sugar stays at 300 mg/dL or above.
• Your breath smells fruity.
• You are vomiting and can't keep food or drinks down.
• You're having trouble breathing.
• You have multiple signs and symptoms of DKA.

High ketones? Call your doctor ASAP‎

If you have DKA, you'll be treated in the emergency room or admitted to the hospital. Your treatment will likely include:

• Replacing fluids you lost through frequent urination and to help dilute excess sugar in your blood.
• Replacing electrolytes (minerals in your body). Too little insulin can lower electrolytes.
• Receiving insulin . Insulin reverses the conditions that cause DKA.
• Taking medicines for any underlying illness that caused DKA, such as antibiotics for an infection.

Diabetes is a chronic disease that affects how your body turns food into energy. About 1 in 10 Americans has diabetes.

For Everyone

Health care providers, public health.

Diabetes & DKA (Ketoacidosis)

Know the warning signs of DKA and check urine for ketones, especially when you're sick.

Diabetic ketoacidosis (DKA) is life-threatening—learn the warning signs to be prepared for any situation.

DKA is no joke, it’s a serious condition that can lead to diabetic coma or even death. DKA is caused by an overload of ketones present in your blood. 

When your cells don't get the glucose they need for energy, your body begins to burn fat for energy, which produces ketones. Ketones are chemicals that the body creates when it breaks down fat to use for energy. The body does this when it doesn’t have enough insulin to use glucose, the body’s normal source of energy. When ketones build up in the blood, they make it more acidic. They are a warning sign that your diabetes is out of control or that you are getting sick.

High levels of ketones can poison the body. When levels get too high, you can develop DKA. DKA may happen to anyone with diabetes, though it is rare in people with type 2. 

Treatment for DKA usually takes place in the hospital. But you can help prevent it by learning the warning signs and checking your urine and blood regularly.

What are the warning signs of DKA?

DKA usually develops slowly. But when vomiting occurs, this life-threatening condition can develop in a few hours. Early symptoms include the following:

• Thirst or a very dry mouth
• Frequent urination
• High blood glucose (blood sugar) levels
• High levels of ketones in the urine

Then, other symptoms appear:

• Constantly feeling tired
• Dry or flushed skin
• Nausea, vomiting, or abdominal pain. Vomiting can be caused by many illnesses, not just ketoacidosis. If vomiting continues for more than two hours, contact your health care provider.
• Difficulty breathing
• Fruity odor on breath
• A hard time paying attention, or confusion 

Warning! DKA is dangerous and serious. If you have any of the above symptoms, contact your health care provider IMMEDIATELY, or go to the nearest emergency room of your local hospital.  

More on ketones and DKA

How do i check for ketones.

You can detect ketones with a simple urine test using a test strip, similar to a blood testing strip. Ask your health care provider when and how you should test for ketones. Many experts advise to check your urine for ketones when your blood glucose is more than 240 mg/dl.

When you are ill (when you have a cold or the flu, for example), check for ketones every four to six hours. And check every four to six hours when your blood glucose is more than 240 mg/dl.

Also, check for ketones when you have any symptoms of DKA.

What if I find higher-than-normal levels of ketones?

If your health care provider has not told you what levels of ketones are dangerous, then call when you find moderate amounts after more than one test. Often, your health care provider can tell you what to do over the phone.

Call your health care provider at once if you experience the following conditions:

• Your urine tests show high levels of ketones.
• Your urine tests show high levels of ketones and your blood glucose level is high.
• Your urine tests show high levels of ketones and you have vomited more than twice in four hours.

Do NOT exercise when your urine tests show ketones and your blood glucose is high. High levels of ketones and high blood glucose levels can mean your diabetes is out of control. Check with your health care provider about how to handle this situation.  

What causes DKA?

Here are three basic reasons for moderate or large amounts of ketones:

• Not enough insulin Maybe you did not inject enough insulin. Or your body could need more insulin than usual because of illness.
• Not enough food  When you're sick, you often don't feel like eating, sometimes resulting in high ketone levels. High levels may also occur when you miss a meal.
• Insulin reaction (low blood glucose)  If testing shows high ketone levels in the morning, you may have had an insulin reaction while asleep.

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Pediatric Diabetic Ketoacidosis (DKA) Clinical Presentation

• Author: William H Lamb, MD, MBBS, FRCP(Edin), FRCP, FRCPCH; Chief Editor: Dale W Steele, MD, MS  more...
• Sections Pediatric Diabetic Ketoacidosis (DKA)
• Practice Essentials
• Pathophysiology
• Epidemiology
• Physical Examination
• Approach Considerations
• Laboratory Studies
• Electrocardiography
• Fluid Replacement
• Insulin Replacement
• Electrolyte Replacement
• Treatment of Cerebral Edema
• Deterrence and Prevention
• Medication Summary
• Volume Expanders
• Antidiabetics, Insulins
• Electrolyte Supplements, Parenteral
• Diuretics, Osmotic Agents
• Media Gallery

When diabetic ketoacidosis occurs as a first presentation of diabetes, symptoms are likely to develop over several days, with progressive dehydration and ketosis. In a small child wearing diapers and with naturally high fluid intake, polyuria and polydipsia are easily missed. When diabetes is developing, the stress and symptoms of another illness may precipitate diabetic ketoacidosis, as well as mask the underlying problem.

Diabetic ketoacidosis can develop very rapidly in a patient with established diabetes, particularly when insulin therapy has been forgotten, deliberately omitted, or disrupted, as with children on continuous subcutaneous insulin infusions or using the newer analogue insulins. Under these circumstances, diabetic ketoacidosis may present with relatively normal blood glucose levels (ie, 250 mg/dL, 15 mmol/L) or less.

Hyperglycemia

Symptoms of hyperglycemia include the following:

Polyuria - Increased volume and frequency of urination

Polydipsia - Thirst is often extreme, with children waking at night to consume large quantities of any available drink

Nocturia and secondary enuresis in a previously continent child

Weight loss - May be dramatic due to breakdown of protein and fat stores

Muscle pains and cramps

Acidosis and dehydration

Symptoms of acidosis and dehydration include the following:

Abdominal pain that may be severe enough to present as a surgical emergency; for children with a failure of continuous subcutaneous insulin infusion, this may be the first presenting sign, along with vomiting

Shortness of breath that may be mistaken for primary respiratory distress

Confusion and coma in the absence of recognized head injury [ 2 ]

Cerebral edema

Presentation of cerebral edema varies; most cases occur 4-12 hours after initiation of treatment. Typically, the child appears to be improving until a sudden deterioration occurs, with increasing coma; fixed, dilated pupils; and, finally, respiratory arrest. Other patients may have a progressively worsening coma. Children may occasionally present with signs of cerebral edema before treatment begins. Regular monitoring of neurologic status to detect early changes, together with prompt corrective treatment, is important to avoid death or damage.

Clinical signs of developing cerebral edema can be divided into 3 main categories. One diagnostic criteria, 2 major criteria, or 1 major and 2 minor criteria have a sensitivity of 92% and false-positive rate of 4%. [ 39 ]

Diagnostic criteria

Abnormal motor or verbal response to pain

Decorticate or decerebrate posture

Cranial nerve palsy (especially III, IV, and VI)

Abnormal neurogenic breathing pattern (eg, Cheyne-Stokes), apneusis

Major criteria

Altered mentation, fluctuating level of consciousness

Sustained and inappropriate bradycardia

Age-inappropriate incontinence

Minor criteria

Abnormally drowsy

Diastolic hypertension (>90 mm Hg)

Additional symptoms

Patients with diabetic ketoacidosis may also have the following symptoms:

Signs of intercurrent infection (eg, urinary tract infection, respiratory tract infection)

Weakness and nonspecific malaise that may precede other symptoms of hyperglycemia

Dehydration may be observed in patients with diabetic ketoacidosis. The degree of dehydration is often reported to be approximately 5-10% but easily can be overestimated (see Table 1, below). One report suggested that children with severe ketoacidosis are rarely more than 8% dehydrated. [ 6 ] Clinical signs such as dry mouth, sunken eyes, and decreased skin turgor, are present from about 3% dehydration. Little correlation with hydration status was found in diabetic ketoacidosis patients when using single biochemical or clinical markers. [ 40 ]

Table 1. Clinical Assessment of Dehydration (Open Table in a new window)

Other symptoms can include the following:

Blood pressure - Usually normal until terminal stages of illness

Tachycardia - May be present

Capillary refill - Initially maintained, but a combination of increasing acidosis and dehydration cause poor tissue perfusion

Kussmaul breathing or deep sighing respiration - A mark of acidosis; these symptoms may be mistaken for status asthmaticus, pneumonia, and even hysterical hyperventilation

Ketone odor - Patient may have a smell of ketones on the breath, although many people cannot detect this smell

Impaired consciousness - Occurs in approximately 20% of patients

Coma - May be present in 10% of patients

Abdominal tenderness - May occur; tenderness is usually nonspecific or epigastric in location; bowel sounds may be reduced or absent in severe cases

Rapid onset of diabetic ketoacidosis that presents with relatively low blood glucose levels, vomiting, and abdominal pain can occur in children using short-acting and long-acting insulin analogues or continuous subcutaneous insulin infusions.

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• Pediatric Diabetic Ketoacidosis. Glasgow Coma Scale, modified for age of verbal response.
• Pediatric Diabetic Ketoacidosis. A graphical representation of the electrocardiographic changes of hypokalemia.
• Pediatric Diabetic Ketoacidosis. A graphical representation of the electrocardiographic changes of hyperkalemia (due to overcorrection of potassium loss).
• Pediatric Diabetic Ketoacidosis. Diabetic ketoacidosis treatment and results chart (page 1 of 4).
• Pediatric Diabetic Ketoacidosis. Diabetic ketoacidosis treatment and results chart (page 2 of 4).
• Pediatric Diabetic Ketoacidosis. Diabetic ketoacidosis treatment and results chart (page 3 of 4).
• Pediatric Diabetic Ketoacidosis. Diabetic ketoacidosis treatment and results chart (page 4 of 4).
• Pediatric Diabetic Ketoacidosis. Carbs for Kids-Count Them In: The Constant Carbohydrates Diet.
• Pediatric Diabetic Ketoacidosis. Diabetes Sick Day Rules.
• Pediatric Diabetic Ketoacidosis. Taking Diabetes Back to School.
• Table 1. Clinical Assessment of Dehydration
• Table 2. Suggested Daily Maintenance Fluid Replacement Rates
• Table 3. Infusion Rates of Potassium Chloride

Contributor Information and Disclosures

William H Lamb, MD, MBBS, FRCP(Edin), FRCP, FRCPCH Consultant Paediatric Diabetologist, Bishop Auckland General Hospital, County Durham and Darlington NHS Foundation Trust, UK William H Lamb, MD, MBBS, FRCP(Edin), FRCP, FRCPCH is a member of the following medical societies: British Medical Association , International Society for Pediatric and Adolescent Diabetes , Royal College of Paediatrics and Child Health , Royal College of Physicians Disclosure: Nothing to disclose.

Dale W Steele, MD, MS Professor of Emergency Medicine, Pediatrics, and Health Services, Policy, and Practice, Warren Alpert Medical School of Brown University; Attending Physician, Department of Pediatric Emergency Medicine, Rhode Island Hospital Dale W Steele, MD, MS is a member of the following medical societies: American Academy of Pediatrics , American Statistical Association , Society for Medical Decision Making Disclosure: Nothing to disclose.

Timothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics , Phi Beta Kappa , Society of Critical Care Medicine , Wisconsin Medical Society Disclosure: Nothing to disclose.

G Patricia Cantwell, MD, FCCM Professor of Clinical Pediatrics, Chief, Division of Pediatric Critical Care Medicine, University of Miami, Leonard M Miller School of Medicine; Medical Director, Palliative Care Team, Director, Pediatric Critical Care Transport, Holtz Children's Hospital, Jackson Memorial Medical Center; Medical Manager, FEMA, Urban Search and Rescue, South Florida, Task Force 2; Pediatric Medical Director, Tilli Kids – Pediatric Initiative, Division of Hospice Care Southeast Florida, Inc

G Patricia Cantwell, MD, FCCM is a member of the following medical societies: American Academy of Hospice and Palliative Medicine , American Academy of Pediatrics , American Heart Association , American Trauma Society , National Association of EMS Physicians , Society of Critical Care Medicine , and Wilderness Medical Society

Disclosure: Nothing to disclose.

Barry J Evans, MD Assistant Professor of Pediatrics, Temple University Medical School; Director of Pediatric Critical Care and Pulmonology, Associate Chair for Pediatric Education, Temple University Children's Medical Center

Barry J Evans, MD is a member of the following medical societies: American Academy of Pediatrics , American College of Chest Physicians , American Thoracic Society , and Society of Critical Care Medicine

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Acknowledgments

The author would like to thank Debbie Matthews and Tim Cheetham for reading the manuscript and for all of their support.

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Introduction and Rationale

Objectives and methodology, 1. terminology, 2. partnership between primary care and specialist hcps, 3. monitoring in children and adolescents, 4. monitoring in adults, 5. when to start insulin, 6. education, 7. psychosocial support, 8. unmet needs for further research, article information, consensus guidance for monitoring individuals with islet autoantibody–positive pre-stage 3 type 1 diabetes.

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Moshe Phillip , Peter Achenbach , Ananta Addala , Anastasia Albanese-O’Neill , Tadej Battelino , Kirstine J. Bell , Rachel E.J. Besser , Ezio Bonifacio , Helen M. Colhoun , Jennifer J. Couper , Maria E. Craig , Thomas Danne , Carine de Beaufort , Klemen Dovc , Kimberly A. Driscoll , Sanjoy Dutta , Osagie Ebekozien , Helena Elding Larsson , Daniel J. Feiten , Brigitte I. Frohnert , Robert A. Gabbay , Mary P. Gallagher , Carla J. Greenbaum , Kurt J. Griffin , William Hagopian , Michael J. Haller , Christel Hendrieckx , Emile Hendriks , Richard I.G. Holt , Lucille Hughes , Heba M. Ismail , Laura M. Jacobsen , Suzanne B. Johnson , Leslie E. Kolb , Olga Kordonouri , Karin Lange , Robert W. Lash , Åke Lernmark , Ingrid Libman , Markus Lundgren , David M. Maahs , M. Loredana Marcovecchio , Chantal Mathieu , Kellee M. Miller , Holly K. O’Donnell , Tal Oron , Shivajirao P. Patil , Rodica Pop-Busui , Marian J. Rewers , Stephen S. Rich , Desmond A. Schatz , Rifka Schulman-Rosenbaum , Kimber M. Simmons , Emily K. Sims , Jay S. Skyler , Laura B. Smith , Cate Speake , Andrea K. Steck , Nicholas P.B. Thomas , Ksenia N. Tonyushkina , Riitta Veijola , John M. Wentworth , Diane K. Wherrett , Jamie R. Wood , Anette-Gabriele Ziegler , Linda A. DiMeglio; Consensus Guidance for Monitoring Individuals With Islet Autoantibody–Positive Pre-Stage 3 Type 1 Diabetes. Diabetes Care 25 July 2024; 47 (8): 1276–1298. https://doi.org/10.2337/dci24-0042

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Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody–positive (IAb + ) children and adults who are at risk for (confirmed single IAb + ) or living with (multiple IAb + ) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings. To inform this monitoring, JDRF, in conjunction with international experts and societies, developed consensus guidance. Broad advice from this guidance includes the following: 1 ) partnerships should be fostered between endocrinologists and primary care providers to care for people who are IAb + ; 2 ) when people who are IAb + are initially identified, there is a need for confirmation using a second sample; 3 ) single IAb + individuals are at lower risk of progression than multiple IAb + individuals; 4 ) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; 5 ) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and 6 ) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasizes significant unmet needs for further research on early-stage type 1 diabetes to increase the rigor of future recommendations and inform clinical care.

Graphical Abstract

Currently, screening of individuals for islet autoantibodies is undertaken as part of programs to detect children, adolescents, and adults who are at higher risk of developing type 1 diabetes due to having a first-degree relative with type 1 diabetes or having a known high-risk HLA genotype. Periodic monitoring of people who have screened positive for one or more autoantibodies (islet autoantibody–positive [IAb + ] individuals) is largely, but not always, conducted within these cohort studies. However, up to 90% of people who develop type 1 diabetes are not part of at-risk groups. Thus, screening programs within the general population are being initiated, and guidance for monitoring in nonspecialist settings is urgently needed. The guidance provided here was developed by a series of expert working groups, convened as part of a JDRF initiative to document the aims, scope, and purpose of monitoring for children, adolescents, and adults with islet autoantibody positivity, along with recommended frequencies of monitoring and actions for health care professionals (HCPs) when risk of progression toward symptomatic type 1 diabetes is high. This includes expert clinical advice for educational and psychosocial support for IAb + individuals, including for their families and caregivers. The expert clinical advice for adults reflects available data, yet it is important to note that there are very limited data in adults aged 45 years and older who are IAb + . It is also important to note that this consensus document does not encompass screening for islet autoantibodies and only provides expert clinical advice for monitoring of individuals who have screened positive for at least one islet autoantibody.

The presence of islet autoantibodies for a presymptomatic period of variable duration in first-degree relatives of individuals with type 1 diabetes has been known for more than 40 years ( 1 ), with recommendations for islet autoantibody screening appearing soon after ( 2 ). Decades of subsequent research and monitoring of individuals with islet autoantibody positivity has led to the paradigm shift that type 1 diabetes is a continuum of stages, from genetic risk through to autoimmunity and then metabolic disease. This has been accompanied by the evolution of descriptive terminology that reflects these stages ( Table 1 ). Similarly, treatment options have moved on from monitoring and managing metabolic disease to include options for modulating the autoimmune response ( 3 , 4 ).

Staging criteria for autoantibody-positive individuals in pre-stage 1 and stage 1–3 type 1 diabetes ( 16–18 )

FPG, fasting plasma glucose; T1D, type 1 diabetes mellitus.

Some people with confirmed persistent prior multiple autoantibody positivity may revert to single autoantibody status or negative status ( 95 ).

CGM is ideally blinded and must be applied and interpreted by a trained HCP. Note, use of CGM-derived criterion did not achieve consensus within the consensus panel and CGM metrics are not part of current ADA or ISPAD guidelines on staging criteria in type 1 diabetes ( 16 , 155 ).

Stage 3 might not include symptoms.

Screening programs have developed to the point that large numbers of children and adults at risk of and with early-stage type 1 diabetes have been intensively followed in longitudinal cohort studies ( 5–15 ) centered on understanding the natural history of progression to symptomatic type 1 diabetes (see Table 2 for a list of studies available for participation). Of note, many entry criteria for individuals with presymptomatic type 1 diabetes into these studies require a family history of type 1 diabetes or HLA genetic risk, and most are focused on pediatric populations. Based on the outcomes of these and other studies, stages of presymptomatic and symptomatic type 1 diabetes are now clinically defined ( Table 1 ) to a degree of clinical consensus ( 16–18 ), although regulatory agencies and research studies may differ in definitions. Using these classifications, individuals can be monitored, diagnosed with diabetes, and even, at times, started on insulin replacement therapy early in the disease course, based on meeting American Diabetes Association (ADA) ( 18 ), International Society for Pediatric and Adolescent Diabetes (ISPAD) ( 16 ), or American Association of Clinical Endocrinology (AACE) ( 19 ) diagnostic criteria. To date, the ISPAD guidelines have provided metabolic and autoantibody monitoring recommendations for children with presymptomatic type 1 diabetes ( 16 ) but do not make specific recommendations for education or psychosocial support in IAb + individuals, monitoring of single IAb + individuals, or when to start insulin. The Fr1da study has suggested and introduced specific recommendations for children ( 20 ). A separate set of recommendations based on a Delphi survey of expert opinion has provided guidance on metabolic and autoantibody monitoring, with recommendations for education and psychosocial support, but does not specifically address adults with early-stage type 1 diabetes ( 21 ). Consequently, to date there is no available guidance on monitoring in adults or in individuals with single islet autoantibody positivity or on when insulin therapy is indicated.

Established population-based screening and monitoring studies in early-stage type 1 diabetes

Note that major research networks are included in the table, but this is not an exhaustive list.

ANZCTR, Australian New Zealand Clinical Trials Registry.

Consensus on evidence-based expert clinical advice for monitoring is an important unmet need, since a positive test for islet autoantibodies ( Table 3 ) is a condition for access to disease-modifying therapies, such as teplizumab ( 22 ). In addition, islet autoantibody screening is anticipated to become more common ( 7 , 23–25 ), highlighting the need for clear monitoring advice.

Autoantibodies against islet autoantigens detected in stage 1–3 type 1 diabetes

IA-2A, insulinoma antigen-2 autoantibody; ICA, islet cell autoantibodies; ICA512, islet cell autoantigen 512; T1D, type 1 diabetes.

Screening efforts are identifying an ever-growing number of IAb + people who warrant education and ongoing monitoring for progression toward clinical diabetes. Evidence shows that such monitoring in research studies can significantly reduce the incidence of diabetic ketoacidosis (DKA) at diagnosis ( 24 , 26–33 ), occurring in up to 70% of unmonitored individuals, which is greatly lowered for individuals participating in follow-up studies ( 26 , 34–39 ). The impact of monitoring in general clinical practice on DKA rates is not known. DKA is a life-threatening condition that requires hospital admission, with significant associated costs for critical care ( 40–42 ). Additionally, in a number of studies, DKA at presentation of type 1 diabetes in youth has been associated with higher HbA 1c that was sustained for up to 11 years after diagnosis ( 43–45 ). Other studies have, however, not found such an association between DKA at presentation of type 1 diabetes and higher long-term glycemic levels ( 46 ). The lack of DKA at onset of type 1 diabetes is also predictive of fewer severe hypoglycemic events 10 years after diagnosis ( 47 ). In this context, the overall goals of monitoring are described in Table 4 .

Purpose of monitoring in IAb + children, adolescents, and adults

T1D, type 1 diabetes; T2D, type 2 diabetes.

Monitoring of people with islet autoantibody positivity outside of research settings will require expert clinical advice that is clear and actionable by HCPs who have limited expertise in diabetes. As indicated, current insights into monitoring progression to clinical type 1 diabetes are largely derived from research studies of individuals known to be at risk for type 1 diabetes, and general population data are less extensive. With this caveat, knowledge on best practices is particularly important for primary care and secondary care physicians who may not frequently see people known to be at risk for type 1 diabetes, and yet who will be tasked with the initial aspects of monitoring following a positive autoantibody screen. Other people who may assist with care of these individuals will include nurse practitioners, physician assistants, diabetes care and education specialists (DCES), psychologists, and other mental and behavioral health professionals, all of whom have a role in supporting IAb + individuals and their families within the monitoring environment. Clear expert clinical advice for monitoring by these groups of HCPs increases the likelihood that individuals at risk for or in early stages of type 1 diabetes, and their families, can receive accurate and actionable education about presymptomatic type 1 diabetes and their individual status.

The Requirement for Monitoring

Islet autoantibodies against four major pancreatic autoantigens are currently clinically available; these consist of insulin autoantibody (IAA), GAD autoantibody (GADA), insulinoma antigen-2 autoantibody (IA-2A) (also called islet cell autoantigen 512 [ICA512]), and ZnT8A ( 48 ). These are often considered “biochemical autoantibodies” and are the screening targets recommended by the most recent ADA Standards of Care ( 25 ). A further islet autoantibody assay, for islet cell autoantibodies, using indirect immunofluorescence on pancreatic tissue, has been used for screening purposes, but it is less available outside of research studies, and the antigenic targets are not fully known. Considerable evidence in multiple populations supports the concept that the number and type of biochemical autoantibodies can be used to predict risk for progression to clinical disease (stage 3 type 1 diabetes) ( Table 1 ). These autoantibodies and their characteristics are described in Table 3 . However, it must be noted that these attributes are derived from observations made in known IAb + populations in the research environment. Further data from studies in IAb + groups in the general population are needed.

Confirmation of IAb + status is important to identify the persistence of the underlying autoimmune response and the validity of the target antigen, although the accuracy of autoantibody tests can vary between laboratories and between target antigens. Therefore, the first positive test should be confirmed with a second test within 3 months ( 49 ) and, where possible, in a laboratory that meets the performance standards set by the Islet Autoantibody Standardization Program (IASP) ( 50 ). Persistent IAb + status on two or more different samples is needed, using sensitive and specific assays with high predictive value for disease progression ( 51 ). Several research programs have tested for islet autoantibody status using capillary sampling to obtain serum or dried blood spots for assessment; however, venous samples are preferred (due to reduced interference from hemolysis) and should be used as confirmation whenever capillary testing has been performed initially.

Predicting when an individual with type 1 diabetes–related autoantibodies may progress to stage 3 type 1 diabetes is difficult. However, in children and adolescents, persistent multiple IAb + status confirms early-stage (stage 1 or stage 2) type 1 diabetes with higher rate of progression to stage 3 type 1 diabetes compared with single IAb + status ( 52 ). For the same reasons as discussed for single IAb + status, confirmation of multiple IAb + status is important, as it indicates early-stage type 1 diabetes and should adhere to the “rule of twos,” i.e., the presence of two different autoantibodies confirmed in two tests from two separate samples ( 51–54 ). Subsequent loss of individual antibodies is not associated with a slower rate of progression. The type of positive autoantibody ( Table 3 ) is also of importance, since, as children age, relative risks for progression with each antibody type will change ( 55 , 56 ), with some evidence that this is also true for adults ( 55 , 57 ). Consideration of these data, along with autoantibody titers, may aid risk stratification ( 58 ). Although fewer data are available in adults, Type 1 Diabetes TrialNet cohort data indicate that the rate of progression to type 1 diabetes in IAb + adults is slower than in children ( 59 ).

Misdiagnosis of type 1 diabetes as type 2 diabetes in adolescents and adults can lead to DKA ( 60 ), as this misdiagnosis means that these individuals are often not started on insulin ( 61 ). Latent autoimmune diabetes of adults (LADA) can also be misdiagnosed as type 2 diabetes ( 62 ), with a risk of delayed insulin initiation. These observations emphasize the value of autoantibody testing for newly diagnosed adults with diabetes, particularly when they have features of type 1 diabetes (e.g., younger age, nonobese, sudden weight loss, mild acidosis, DKA, hyperglycemia >16.7 mmol/L [>300 mg/dL]) ( 63 ), for making an accurate diagnosis and starting appropriate treatment. It is, however, important to recognize that some individuals with new-onset type 1 diabetes have a phenotype that does not differ substantially from people with type 2 diabetes, particularly given the increased prevalence of obesity ( 60 , 64 ). Misdiagnosis of maturity-onset diabetes of the young (MODY) is also reported ( 65 ), suggesting that islet autoantibody screening can be valuable at presentation of all forms of diabetes.

An important outcome of monitoring individuals with islet autoantibody positivity is to inform the decision to initiate insulin therapy, and this is an area of evolving practice. In some centers, individuals with hyperglycemia ( Table 5 ) but with HbA 1c <48 mmol/mol (<6.5%) might not be started on insulin without the presence of symptoms. Sequential HbA 1c monitoring has been productive in this context in pediatric studies on individuals with islet autoantibody positivity, since an absolute ≥10% increase from baseline, even if the HbA 1c test reading stays below 48 mmol/mol (6.5%), is predictive of disease progression ( 66 , 67 ) within a median of 1 year. Risk of progression within 2 years following a confirmed ≥10% increase in HbA 1c is lower for older individuals. This aspect of stage 3 type 1 diabetes (i.e., when to start insulin once hyperglycemia is confirmed) requires further evidence to support clinical practice to better understand the metabolic and mental health outcomes.

Attributes of current monitoring methods

DPTRS, Diabetes Prevention Trial-Type 1 risk score; GDM, gestational diabetes mellitus; M60, 60 min test result; M120, 120 min test result; PLS, partial least squares; PPV, positive predictive value; T1D, type 1 diabetes; T2D, type 2 diabetes.

Used in research settings for staging progression of impaired glucose tolerance as C-peptide provides important predictive value.

Used in clinical practice to detect impaired glucose tolerance in prediabetes and gestational diabetes mellitus.

Use of CGM-derived criterion did not achieve consensus within the consensus panel, with further evidence required to confirm findings to date.

What Should Be Monitored?

It is acknowledged that the practice of monitoring of individuals with islet autoantibody positivity must accommodate different settings with diverse health care resources. In this context, there are multiple available tools for monitoring, including self-monitored blood glucose (SMBG), periodic continuous glucose monitoring (CGM), standard oral glucose tolerance test (OGTT), random venous glucose, HbA 1c , and repeat islet autoantibody monitoring. In this context, serial stimulated C-peptide measurement during an OGTT can be used to assess deterioration of β-cell function and to predict risk development of type 1 diabetes ( 68 ). Since individuals who present with clinical type 1 diabetes (stage 3) often have significant residual β-cell function ( 69 ), they may benefit from therapies that can optimize prolongation of insulin secretion ( 70 ).

The pros and cons of each monitoring method are documented in Table 5 . Identification of an increase in sequential HbA 1c values from a baseline reading can be as informative as 2-h OGTT values in predicting risk of stage 3 type 1 diabetes in youth with genetic risk and type 1 diabetes–associated autoantibodies ( 66 , 67 ). Ongoing research continues to evaluate the role of CGM (including professional CGM, which is blinded to the user) in aiding in the identification of individuals, including those with a normal OGTT, who are likely to rapidly progress to stage 3 type 1 diabetes ( 71–73 ). To date, use of CGM metrics in individuals who have multiple IAb + status has been shown to be predictive of progression to type 1 diabetes, but CGM measures are not yet as sensitive as OGTT testing ( 74 ).

Where Should Monitoring Take Place?

In practice, monitoring should be carried out wherever the skills and resources exist to perform the appropriate tests ( Table 5 ). However, since many people will be monitored in primary care, there is a need to consider different intensities of monitoring consistent with resources available. The capabilities of primary care HCPs and other care providers should be applied to monitoring of early-stage type 1 diabetes without the need to refer to an expert practitioner until clinically appropriate. In primary care, this may help specify basic education about symptoms and glycemic signposts. It is understood that, compared with stage 1, monitoring in stage 2 type 1 diabetes may require more expert practitioners.

The aim of this international consensus report is to formulate expert clinical advice, based on current evidence and expert opinion, that specifies the required monitoring and management approach for people who have been identified as having IAb + status and pre-stage 3 type 1 diabetes, and can be used in daily clinical practice. Overall, these key principles should encompass 1 ) who should be monitored; 2 ) which end points to monitor; 3 ) the frequency and duration of monitoring; 4 ) initiation of insulin during stage 3 type 1 diabetes; and 5 ) how to provide psychosocial and educational support for affected individuals and families.

We acknowledge that monitoring of IAb + individuals will occur in diverse settings, with variable resources to support effective monitoring of IAb + individuals. Thus, a guiding principle of this consensus report is to provide advice that is straightforward and actionable within the landscape of available clinical skills and resources, wherever the monitoring will take place. The audience for this consensus document, therefore, includes 1 ) primary care providers; 2 ) endocrinologists and diabetologists; 3 ) DCES; 4 ) mental and behavioral health professionals; and 5 ) individuals at risk for or in early stages of type 1 diabetes and their families.

Methodology

The consensus process was initiated by the JDRF with a conference held on 21 February 2023 at the 16th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD) in Berlin, Germany, with in-person or virtual attendance. M.P. served as Chair of the project and L.A.D. served as Vice Chair. A mission statement was created, and the attendees were invited by email from JDRF and the consensus project leadership. The initial working group comprised 61 internationally recognized physicians, nurse practitioners, clinical psychologists, and DCES with expertise in the diagnosis and care of people with early-stage type 1 diabetes. The conference was centered on monitoring of IAb + people in early-stage type 1 diabetes, including discussions of current guidance on current best practice for monitoring, as applied by several prospective type 1 diabetes prevention trials (discussed in detail below).

Following a moderated discussion, expert participants were offered the opportunity to join at least one of four working groups, each focused on key aspects of monitoring. Each working group was chaired by two expert contributors, as noted below, and was tasked with self-organized review of the available evidence, participation in serial online discussions, and development of core principles. The working groups were 1 ) monitoring in children and adolescents (Chairs: R.E.J.B. and K.J.G.); 2 ) monitoring in adults (Chairs: R.S.-R. and J.M.W.); 3 ) educational needs (Chairs: K.J.B. and B.I.F.); and 4 ) psychosocial interventions (Chairs: K.A.D. and L.B.S.). This subsequently generated 21 separate online group discussions. Each aspect of these discussions was documented with support from JDRF team members and a medical writer. It must be noted that this document is not intended or structured as a systematic review.

On a weekly basis, from 3 May 2023 onwards, evidence-based statements and expert interpretations were drafted for review and revision. At the end of this iterative process, an agreed narrative review of the available evidence was compiled along with the expert clinical advice. Each bulleted principle was assigned a level of supporting evidence (A, B, C, or E; see Supplementary Table 1 ) that adheres to the evidence-grading system for Standards of Care in Diabetes—2023 , published by the ADA ( 75 ). The process concluded with a conference to review and endorse the penultimate consensus report at the ADA’s 83rd Scientific Sessions in San Diego, CA. Following this meeting, a revised draft was made available for public comment, after which the consensus document was finalized. The outcomes of this process are also summarized in an algorithm that details the decision path for monitoring of IAb + people regardless of whether they were screened as part of a research protocol or in the clinical setting for any reason ( Fig. 1 ).

Algorithm for monitoring of people screened positive for one or more islet autoantibodies. *Monitoring frequency and methodology depends on age, length of time since first detection of islet autoantibody, number of islet autoantibodies detected, and presence of symptoms of type 1 diabetes (see Table 1 and Tables 3 – 5 ). Ab, antibody; GP, general practitioner; PRN, pro re nata (as needed); Sx, symptoms; T1D, type 1 diabetes.

Precise and consistent language is important to facilitate clear communication and education. As the field has evolved, so has the language around multiple IAb + status, the stages of type 1 diabetes, and associated risk of progression. It was once commonplace to refer to “risk of” and “prevention of” type 1 diabetes in individuals with multiple IAb + status. However, the staging criteria recognize seroconversion to multiple IAb + status as the onset of early-stage type 1 diabetes and, thus, it is not possible to both have a condition and be “at risk” for it.

Therefore, stage 1 type 1 diabetes and stage 2 type 1 diabetes ( Table 1 ) should be referred to by their defined names or collectively referred to as “early-stage type 1 diabetes.” While the staging criteria are still becoming widely known, it may be appropriate to refer to these stages as “presymptomatic type 1 diabetes” for some audiences to highlight that these early stages exist prior to traditional, symptomatic (i.e., stage 3 type 1 diabetes) disease. Individuals with a genetic risk (based on genetic screening and/or family history) or with only single IAb + status have pre-stage 1 type 1 diabetes and can be referred to as at risk, but individuals with multiple IAb + status are confirmed as having early-stage type 1 diabetes. It must also be clear what the focus of prevention is; for example, prevention of seroconversion, progression to dysglycemia or of stage 3 type 1 diabetes.

There is a need for primary care to take on some of the early-stage monitoring and managing of IAb + children and adults. However, staging criteria are relatively new and are unlikely to be widely known among primary care HCPs. Therefore, educational steps and materials must facilitate the partnership between primary care HCPs and secondary care. Primary care HCPs in some regions (e.g., the U.S. and Europe) are involved in screening and monitoring tasks for hypercholesterolemia and other metabolic syndromes, so the expectation is that this is possible for early-stage type 1 diabetes. A critical need is that all HCPs recognize that some IAb + individuals can progress rapidly, whereas others may not develop symptoms for decades. In this context, the following expert clinical advice is suggested.

Clinical Roles and Responsibilities

Primary care HCPs should understand the stages of type 1 diabetes as well as methods for and suggested frequency of metabolic monitoring that can be used to prevent DKA at onset of clinical type 1 diabetes. [E]

Primary care HCPs with a specific interest in managing people with early-stage type 1 diabetes can serve as a local referral resource for other primary care HCPs when specialist care providers are not readily accessible. [E]

The primary care provider and specialty care provider, along with the at-risk single IAb + individual or the multiple IAb + individual with early-stage type 1 diabetes and their family, should determine which provider will have primary responsibility for metabolic monitoring and what degree of collaboration is desired. [E]

The level of specialist engagement will need to be reassessed and may shift over time as the IAb + individual progresses through the stages of type 1 diabetes as well as when other needs and circumstances change. [E]

Communication and Coordination of Care

Within a medical practice, HCPs should ensure that the medical record for a child, adolescent, or adult, who is single or multiple IAb + , reflects their status and their individual plan for routine metabolic follow-up and for urgent evaluation if symptoms of hyperglycemia develop. [E]

If an IAb + individual meets the criteria for stage 2 type 1 diabetes ( Table 1 ), a referral should be made to a diabetologist/endocrinologist to discuss early treatment options and individualized risk of progression to clinical type 1 diabetes. [E]

If an IAb + individual develops symptomatic hyperglycemia, an immediate consultation with, and referral to, a multidisciplinary diabetes team comprising specialists with training and expertise in diabetes is necessary. [E]

Training and Skills Development

Both monitoring and education require a broader understanding of early-stage type 1 diabetes across the medical community. Inclusion of an understanding of the continuum of type 1 diabetes into all levels of medical and nursing education will require development of competencies appropriate to the role ( Fig. 2 ). [E]

The continuum of educational needs and competencies: what does one need to know? The image represents the anticipated skills that must be developed within the continuum of stakeholders in monitoring presymptomatic type 1 diabetes. The groups indicated within the pyramid sections should have the competencies described and participate as appropriate. The need is for unified, consistent, globally applicable language at all levels. T1D, type 1 diabetes.

The Current Landscape of Monitoring Children and Adolescents in Early-Stage Type 1 Diabetes

The following section encompasses monitoring of children and adolescents aged up to 17 years. The overall algorithm is summarized in Fig. 1 . For a young person who has screened positive for multiple IAb + status, monitoring recommendations are also provided by the ISPAD ( 16 ) and the Fr1da study ( 20 ).

This expert clinical advice emphasizes the need to benchmark the glycemic stage of disease and to offer ongoing monitoring for disease progression, which should be appropriate to the needs of the affected person and their family. At present, standard 2-h OGTT (1.75 g of glucose per kg of body weight up to 75 g maximum) is the preferred modality, particularly for inclusion in research studies, whereas less intensive methods are suggested for children or adolescents who decline to undertake OGTT or participate in a research protocol. Even in a clinical study setting, adherence with OGTT monitoring can be low ( 76 ). Given the diverse settings and resources available, among the monitoring tools identified ( Table 5 ), HbA 1c testing is not suitable outside of the clinical setting and only random glucose assessments, routine SMBG and CGM, that do not require venipuncture can be self-managed at home. Studies using CGM in small cohorts of children and youth with stage 1 or stage 2 type 1 diabetes have suggested that glucose levels ≥7.8 mmol/L (≥140 mg/dL) for >10% of each day is associated with an 80% risk of progression to type 1 diabetes within 12 months of the CGM assessment period ( 72 , 77 ). In this context, risk of progression to stage 3 type 1 diabetes within 2 years of baseline CGM assessment was 40% in individuals with early-stage type 1 diabetes who spent ≥5% of each day with glucose ≥7.8 mmol/L (≥140 mg/dL) ( 71 ). These outcomes indicate a need for more evidence to confirm the emerging value of CGM in monitoring individuals with early-stage type 1 diabetes and to understand the disease-predictive value of additional CGM metrics. This need is more pressing given that home use of CGM systems and CGM-derived glycemic metrics is being evaluated for risk stratification for healthy relatives of people with type 1 diabetes ( 78 , 79 ).

Monitoring at a 6- to 12-monthly cadence has been used for participants in prevention trials, depending on risk stratification. More frequent monitoring can be indicated for children who screen positive for islet autoantibodies before 3 years of age and are at high risk of progression ( 24 , 51 ), for example, at 3- to 6-monthly intervals, depending on staging ( 24 ). It should be noted that, among monitoring tools, not all CGM systems are generally available in all regions, or for use in very young children. For all individuals outside of the research setting, reducing the frequency of monitoring can be considered as part of a minimally burdensome approach, and modeling studies suggest this can be achieved while meeting the goal of DKA prevention on a population level ( 80 ). In this context, youth of Black race and/or Hispanic ethnicity are less likely to participate in monitoring ( 81 ).

Monitoring for Single IAb + At-Risk Children

Evidence from cohort studies indicates that up to 50% of children with single IAb + status revert to being islet autoantibody negative (IAb − ) ( 82 , 83 ). Children with confirmed persistent single IAb + status are not at high risk for progression compared with those with multiple IAb + status, with one population-based study indicating that the 10-year risk of progression to type 1 diabetes for persistent single IAb + children is 14.5%, with most of that progression (10%) happening in the first 2 years after becoming IAb + ( 51 ). This analysis also showed that the progression rate is higher for young children who have single IA-2A positivity (40.5%) compared with GADA positivity (12.9%) or IAA positivity (13.1%) ( 51 ); however, it must be noted that fewer than 10% of children with single IAb + status are IA-2A + . Younger age (<5 years) at first single-confirmed islet autoantibody positivity is a risk factor for progression to multiple islet autoantibody positivity, particularly during the first 2 years after seroconversion ( 84 , 85 ). As children age, relative risk for progression with each antibody subtype changes ( 56 ), with an increased effect for GADA with increasing age and a reduced effect for IAA ( 86 ).

For young children, evidence indicates that metabolic and autoantibody monitoring frequency in the first 2 years after first detection of an autoantibody is key, as this is when spread from at-risk single islet autoantibody positivity to early-stage type 1 diabetes with multiple islet autoantibody positivity is most likely. Following confirmed single IAb + status, the IAb + evolution after 2 years predicts development of clinical type 1 diabetes ( 87 ). Progression to multiple IAb + status or reversion is also highest in the first 2 years in single IAb + preschool children, with a hazard rate of 0.3 in the first 2 years versus 0.05 for children who have been single IAb + for >2 years ( 84 ). Among children with increased genetic risk, those who remain single IAb + have a risk for type 1 diabetes of 1.8 per 100 person-years, children who revert to negative status have a risk of 0.14 per 100 person-years, and children who have never been IAb + have a risk of 0.06 per 100 person-years ( 83 ). The rate of progression to multiple IAb + status also declines with age ( 88 ).

Expert Clinical Advice for Monitoring of Single IAb + (At-Risk) Children

Confirm persistent single IAb + status after first detection in a second sample, preferably in a laboratory that meets IASP standards, using two independent methods ( 89 ), and confirm negative status for other islet autoantibodies. [B]

Islet autoantibody status and metabolic monitoring during the first 2 years after seroconversion is most critical ( 51 , 84 , 85 , 90 ). Ongoing metabolic monitoring is not essential beyond this 2-year period. [B]

Children who develop type 1 diabetes at a very young age have more rapidly progressing and aggressive disease. For children aged <3 years who are single IAb + , monitor their IAb + status every 6 months for 3 years, then annually thereafter for 3 more years. Metabolic monitoring in children aged <3 years should include random venous or capillary blood glucose and HbA 1c values at the same frequency ( 51 , 84 , 85 , 87 , 90 ). If no progression, stop autoantibody and metabolic monitoring and counsel for risk of clinical disease. [B]

For children aged ≥3 years at first positive test, monitor IAb + status annually for 3 years. Metabolic monitoring should include annual random venous or capillary blood glucose and HbA 1c testing for 3 years ( 51 , 84 , 85 , 90 ). If no progression after 3 years, stop autoantibody and metabolic monitoring and counsel for risk of clinical disease ( 51 , 84 , 85 , 90 ). [C]

For children with single islet autoantibody positivity who revert to seronegative during autoantibody monitoring or do not progress (see above), education should be provided to their families emphasizing potential symptoms and awareness of DKA ( 33 , 91 , 92 ). [C]

Many data on single IAb + children are derived from groups with extended prospective follow-up and known genetic risk profiles or first-degree relatives with type 1 diabetes with limited racial/ethnic diversity. Data on individuals in the general population are more limited, particularly in those with a single screening event.

Monitoring for Multiple Autoantibody-Positive Children (Early-Stage Type 1 Diabetes)

Children with confirmed multiple IAb + status are at very high risk for progression to stage 3 type 1 diabetes within 15 years. Combined data from five prospective studies indicate that the 15-year risk for stage 3 type 1 diabetes is 85% for children with two islet autoantibodies and 92% for those with three islet autoantibodies, and that there is a >99% lifetime risk ( 87 ). In children with multiple islet autoantibody positivity, younger age at first islet autoantibody detection predicts more rapid progression to stage 3 type 1 diabetes ( 51 , 93 ). Although data on children with multiple islet autoantibody positivity identified from general population screening are derived from shorter follow-up durations, progression rates appear to be similar to those observed in relatives of individuals with type 1 diabetes enrolled in longitudinal research cohort studies ( 24 , 94 ).

The detection of multiple autoantibodies should be confirmed in a venous sample, within 3 months ( 49 ). However, this should not be a rate-limiting step in the monitoring or treatment process, as progression can happen rapidly in young children. Confirmation is critical, since without it there is a risk of delivering a false diagnosis of multiple IAb + status, with consequent anxiety and distress for the individual. Conversely, although loss of confirmed multiple IAb + status is rare and may be associated with reduced risk of progression to type 1 diabetes ( 95 ), monitoring should not be discontinued in this group.

Expert Clinical Advice for Monitoring of Multiple IAb + Children (Early-Stage Type 1 Diabetes)

Monitoring of glucose metabolism among children with multiple IAb + status is necessary to predict time to stage 3 diagnosis, identify those who may be eligible for intervention, and prevent DKA. Options for metabolic assessments include home SMBG monitoring, periodic CGM assessment, and laboratory testing for HbA 1c , random venous or capillary blood glucose, and OGTT (with stimulated C-peptide assessments). It is acknowledged that there is variable access to high-quality laboratory testing facilities outside of the research setting. Where possible, the opportunity to undertake monitoring at home or in the primary care setting should be considered ( Table 5 ).

Education must be provided to reinforce the need for and value of longitudinal monitoring to prevent DKA ( 33 , 91 , 92 ). Written instructions with relevant emergency contact details should be provided in case of type 1 diabetes symptoms and/or hyperglycemia. [E]

Confirm persistent multiple IAb + status after first detection in a second sample, preferably in a laboratory that meets IASP standards, following the rule of twos ( 52 ), preferably using two independent methods ( 89 ). [B] Where a two-test confirmation is not possible, a single blood test positive for multiple islet autoantibody status identifies a person with sufficient risk for metabolic monitoring. [E]

In infrequent cases, for a child with previously confirmed multiple IAb + status and who has reverted to single IAb + or IAb − status ( 95 ), monitoring should also follow the advice below. [E]

Metabolic monitoring should be conducted based on the staging criteria and modalities described in Tables 1 and 5 . This should be undertaken when the child is healthy and not experiencing intercurrent illness. [E]

SMBG meters and strips can be provided to all children with multiple islet autoantibody positivity or their parents. [E]

During intercurrent illness, SMBG can be used to detect hyperglycemia. [A]

For children with recent confirmation of multiple IAb + status, an SMBG test can be performed on two different days over a 2-week period (on each day, test either fasting or postprandial) and again thereafter once every 1–3 months. See also advice below. [E]

In children with stage 1 type 1 diabetes, HbA 1c should be measured once every 3 months for children <3 years old, at least every 6 months for children 3–9 years old, and at least every 12 months for children >9 years old ( 93 ). [E] Increase in longitudinal HbA 1c of ≥10%, even in the normal range (e.g., from 31 mmol/mol [5.0%] to 37 mmol/mol [5.5%]), indicates increased risk of disease progression to stage 3 type 1 diabetes within a median of 1 year ( 66 , 67 ). [B]

In children with stage 2 type 1 diabetes, measures of glucose regulation should be monitored every 3 months, as above. [E]

Longitudinal change in HbA 1c of ≥10% from date of confirmed islet autoantibodies may indicate dysglycemia and disease progression ( 66 , 67 ), and requires the performance of an OGTT to assess type 1 diabetes stage ( Table 1 ) in order to determine eligibility for therapy. [E]

Random venous or capillary blood glucose should be measured at the same time as HbA 1c . Rise in venous glucose in children with multiple IAb + status predicts time to stage 3 type 1 diabetes ( Table 1 ) ( 96 ). [E]

OGTT is the established gold standard to classify stage 1, stage 2, or stage 3 type 1 diabetes [A], but if performing OGTT is not possible, obtain a 2-h postprandial capillary blood glucose after a carbohydrate-rich meal to assess for dysglycemia ( 86 ). [E]

Monitor objective weight trends in a growing child using a growth chart, [C] which may be below the normal range during progression of type 1 diabetes. Ensure that a healthy meal plan has been maintained to preclude disordered eating behaviors as a cause of weight change. [E]

Ten- to fourteen-day CGM can be used periodically to monitor glucose metabolism at a similar frequency as HbA 1c measurement. [E] CGM should ideally be blinded to the individual wearing it and must be interpreted by trained HCPs, with education for the user and their family. [E] Criteria for CGM metrics to diagnose stage 2 or stage 3 type 1 diabetes are proposed ( Table 1 ) and require further research.

Stage 2 type 1 diabetes warrants referral to specialists in type 1 diabetes progression for discussion of risk and options for monitoring, wherever feasible. [E]

In countries with approved therapeutic options for early-stage type 1 diabetes or locations with access to intervention studies ( 3 , 97 ), referral to a clinical center with expertise in the specific treatment should be done when stage 2 type 1 diabetes is suspected or diagnosed. [E]

The Current Landscape of Monitoring Adults Who Are at Risk of or Have Early-Stage Type 1 Diabetes

The following guidance encompasses monitoring of adults aged 18 years and over, although the advice is based on outcome data that typically reflect adults younger than 45 years of age. Data specific to adults older than this are an important unmet need. Epidemiological data show that, overall, type 1 diabetes is diagnosed more frequently in adulthood than in childhood ( 98–101 ), at a median of more than 35 years of age ( 102 , 103 ). Despite this, misdiagnoses of type 1 diabetes in adults remain common and are increasingly likely with age ( 60 ), setting the scene for development of DKA. In common with childhood-onset type 1 diabetes, adult-onset type 1 diabetes is associated with the presence of islet-specific autoantibodies ( 104–107 ). Although TrialNet cohort data indicate that the rate of progression to type 1 diabetes in IAb + adults is slower than that in children, many adults with multiple IAb + status and early-stage type 1 diabetes still develop stage 3 disease ( 59 ). While it has been suggested that progression in some adults may not occur and that some of those who do progress have only single islet autoantibody positivity, further long-term follow-up data are needed to better characterize the long-term implications of persistent autoimmunity in adults ( 108 ). For example, recent data highlight the frequent presence of islet autoimmunity in cohorts presenting with phenotypic type 2 diabetes ( 109 ).

Guidance to inform clinical monitoring practices in adults represents a considerable unmet need. There are many evidence-base gaps, including a lack of information about risk of disease progression in IAb + adults without a family history of type 1 diabetes, particularly in individuals with non-European ancestry. Data on suggested monitoring protocols, including effectiveness in preventing DKA and adherence with monitoring, are substantially based on children and adolescents. The frequency of DKA among adults at diagnosis with type 1 diabetes is unknown but believed to be lower than that for children, given that adults may recognize and respond to symptoms of hyperglycemia and often have higher C-peptide levels at clinical diagnosis and a slower decline in β-cell function over time ( 110 ). However, incorrect assumptions leading to underdiagnosis of type 1 diabetes in adults mean many develop DKA before starting insulin therapy.

DKA incidence at clinical diagnosis can be reduced by participation in active monitoring ( 24 , 26 , 27 ). Regarding frequency of monitoring, modeling based on TrialNet data suggests that conducting approximately half the number of visits involved in a research setting (typically once every 12 months rather than every 6 months) is likely to be effective in substantially reducing the incidence of DKA to the levels seen in research studies both for children and adults ( 80 ). However, data from the TrialNet study indicate that adults 18 years and older are less likely than pediatric participants to engage with recommended monitoring using 6–12 monthly OGTT in the early phases after screening positive for autoantibodies ( 81 ). As with youth, adults of Black race and/or Hispanic ethnicity are less likely to participate with monitoring in this context ( 81 ).

Most endocrinologists and primary care HCPs will not be trained in monitoring adults with single IAb + status or early-stage type 1 diabetes. Thus, the educational need will be significant. As with children and adolescents, monitoring in IAb + adults must be realistic and actionable across diverse regions with different resources. HCPs are significantly burdened such that additional tasks for monitoring in pre-stage 3 type 1 diabetes must be clinically useful.

Monitoring for Single Autoantibody-Positive At-Risk Adults

Frequency of monitoring can be based on the stage at which an individual with islet autoantibody positivity is diagnosed. Single IAb + adults with dysglycemia should be monitored more frequently than those with normoglycemia. Additional risk stratification may also be possible based on other characteristics, such as age, or modifiable factors, such as abdominal obesity.

Expert Clinical Advice for Monitoring Single IAb + (At-Risk) Adults

Annual metabolic monitoring should be considered for single IAb + adults if there are additional risk factors, including one or more of the following: first-degree relative with type 1 diabetes; elevated genetic risk for type 1 diabetes if tested; dysglycemia (e.g., impaired fasting glucose or impaired glucose tolerance); or history of stress hyperglycemia ( 111 , 112 ). [E]

Although single IAb + adults are at lower risk of progression to type 1 diabetes compared with children ( 59 ), and this risk continues to fall with increasing age, there remains a residual risk for progression. The approach to metabolic monitoring for single IAb + adults can be informed by that applied for screening for type 2 diabetes, which is advised every 3 years for normoglycemic adults aged >35 years or who have overweight/obesity with one or more additional risk factors ( 18 ). A similar 3-year frequency is proposed for single IAb + adults to monitor for risk of progression, which may be increased to annual monitoring with the additional risk factors identified for type 2 diabetes. [E]

No type 1 diabetes monitoring is indicated in individuals with transient single islet autoantibody positivity who then revert to being seronegative. Screening for diabetes in this group of adults should, thereafter, follow standard-of-care guidelines for type 2 diabetes ( 18 ). [C]

Monitoring for Multiple Autoantibody-Positive Adults (Early-Stage Type 1 Diabetes)

As with monitoring in single IAb + adults, more frequent monitoring is proposed for individuals with multiple IAb + status if they are diagnosed with stage 2 type 1 diabetes compared with stage 1 type 1 diabetes. Risk stratification based on age, abdominal obesity, and other modifiable factors also applies.

Expert Clinical Advice for Monitoring Multiple IAb + (Early-Stage Type 1 Diabetes) Adults

Confirm persistent multiple IAb + status after first detection in a second sample, following the rule of twos ( 52 ) and preferably using two independent methods ( 89 ). [ B] Where a two-test confirmation is not possible, a single blood test positive for multiple islet autoantibody status identifies a person with sufficient risk for metabolic monitoring. [ B]

In infrequent cases, for adults with previously confirmed multiple IAb + status who have reverted to single IAb + or IAb − status ( 95 ), monitoring should also follow the advice below. [E]

All multiple IAb + adults can be provided with SMBG meters and strips to be used during illness or when symptoms may be present. [E]

In adults with stage 1 type 1 diabetes and normoglycemia ( Table 1 ), glycemic status should be monitored using HbA 1c every 12 months as part of routine primary care visits. Modify frequency of monitoring based on individual risk assessment, based on age, number and type of islet autoantibodies, and glycemic metrics ( 4 ). [E]

If duration of normoglycemia extends to 5 years, metabolic monitoring every 2 years may be sufficient. [E]

In adults with confirmed stage 2 type 1 diabetes ( Table 1 ), metabolic status should be monitored using HbA 1c every 6 months, in conjunction with one other of the following monitoring modalities: blinded CGM (applied and interpreted by trained HCP); higher frequency of SMBG; or 2-h plasma glucose following 75-g OGTT. [E]

Longitudinal change in HbA 1c of ≥10% from date of confirmed islet autoantibodies may indicate dysglycemia and disease progression ( 66 , 67 ), and it requires the performance of an OGTT to assess type 1 diabetes stage ( Table 1 ) to determine eligibility for therapy. [E]

When dysglycemia or hyperglycemia occurs, C-peptide monitoring should be considered where the diagnosis of type 1 diabetes versus type 2 diabetes is unclear. Meta-analysis indicates that a C-peptide level of ≤0.20 nmol/L with IAb + status can be associated with a diagnosis of type 1 diabetes rather than type 2 diabetes ( 113 ); however, many adults presenting with type 1 diabetes will have C-peptide above this level ( 110 ). [B] Note that C-peptide levels can be falsely low in hypoglycemia (<3.9 mmol/L [<70 mg/dL]), after fasting, or in severe hyperglycemia/DKA, so concomitant plasma glucose concentration should be checked and interpreted in combination with the clinical state.

In countries with approved therapeutic options for early-stage type 1 diabetes or locations with access to intervention studies ( 3 , 96 ), referral to a clinical center with expertise in the specific treatment should be done when stage 2 type 1 diabetes is suspected or diagnosed. [E]

Monitoring During Pregnancy for IAb + Women

Evidence on the progression of type 1 diabetes in IAb + pregnant women is limited, and research data on this aspect of managing risk in early-stage type 1 diabetes is a significant unmet need ( Table 6 ). With that said, a high risk for postpartum type 1 diabetes has been indicated ( 114 ), and the guidance below is primarily based on expert opinion. Pregnancy demands increased pancreatic β-cell function and may result in diabetes, as it does in gestational diabetes mellitus (GDM) ( 115 ). Given that 60% of babies born to women with diagnosed type 1 diabetes are large for gestational age (LGA), which is associated with increased rates of obstetric and neonatal complications ( 116 , 117 ), it is important to avoid a missed early diagnosis and promote normal fetal development.

Selected unmet needs for further research and clinical development

The key principles presented in this table and in this consensus document will be subject to updating once additional evidence becomes available.

T1D, type 1 diabetes.

Expert Clinical Advice for Monitoring in Pregnancy for IAb + Women

Women with confirmed islet autoantibody positivity who become pregnant should have an OGTT, HbA 1c test, or application of CGM soon after pregnancy is confirmed (by 8 weeks if possible) ( 18 , 118 ). [C]

Women with confirmed islet autoantibody positivity who are not already diagnosed with type 1 diabetes should receive OGTT tests at 24–28 weeks of pregnancy, as standard for all pregnancies ( 18 ). [A]

Glucose monitoring for women with confirmed IAb + status who are diagnosed with type 1 diabetes: once postpartum, women should be assessed prior to discharge from hospital, in consultation with a specialist endocrinologist, to determine continued need for insulin ( 114 ). [C]

Women with confirmed IAb + status should be monitored for 6–12 months postpartum to assess any changes in insulin requirement. [E] Where available, follow-up both with the gestational care provider and an insulin initiation specialist should be provided. [E]

At some point, monitoring will reveal a person with persistent and/or recurrent hyperglycemia, prompting a decision on whether to start insulin, along with associated education and support for affected individuals and their families. As screening programs identify more people with early-stage type 1 diabetes, more people are being assessed as meeting classic diagnostic criteria for stage 3 type 1 diabetes ( Table 1 ) but who might not yet require insulin therapy. Decisions about how and when to initiate insulin will be based on a range of factors, many of which do not have a body of evidence. Therefore, consideration of starting insulin should trigger a referral to a specialist center with expertise in initiating and managing people with type 1 diabetes on insulin.

The primary goals of education for the care of IAb + individuals and their families are outlined in Table 7 . Given the paucity of evidence on education for people with early-stage type 1 diabetes, extensive experience in education for stage 3 type 1 diabetes can be extrapolated to this population. National standards for diabetes self-management education and support (DSMES) have been published by the ADA and the Association of Diabetes Care & Education Specialists (ADCES) and are broadly applicable in this context ( 119 ). When appropriate, evidence from studies in stage 3 type 1 diabetes are used to support grading of evidence.

The primary goals of education for care of IAb + individuals and their families

Experience in clinical studies can also inform education for people with early-stage type 1 diabetes and their families/caregivers. The Environmental Determinants of Diabetes in the Young (TEDDY) prospective study protocol emphasizes parental education regarding symptoms and signs of diabetes. For families new to type 1 diabetes, this education provides foundational skills for diabetes management that are a component of reduced parenting stress at the time of stage 3 diagnosis compared with individuals who were members of the community control group and did not receive education ( 120 ). Similarly, families of children with early-stage type 1 diabetes in the Fr1da study are invited to participate in an educational program of blood glucose monitoring and symptoms of hyperglycemia/DKA. They are also provided with a guidebook specifically designed for children with early-stage type 1 diabetes and assigned a contact person to answer questions at any time. Children who take part in this program alongside metabolic monitoring have a lower rate of DKA and reduced HbA 1c at stage 3 type 1 diabetes presentation compared with children who declined education and follow-up ( 33 ). Over 50% had no symptoms at the clinical presentation of stage 3 type 1 diabetes, 93.5% had no weight loss, and length of stay in hospital was shorter ( 91 , 92 ).

Basic community awareness campaigns not associated with monitoring and centered on the early symptoms of type 1 diabetes that target teachers, pediatricians, and parents have been effective in reducing DKA rates in children in regional settings (Parma in Italy [ 121 ] and Newcastle in New South Wales, Australia [ 122 ]). However, national campaigns in Italy and Austria, with the same objectives, have not seen the same impact ( 123 , 124 ). The content and delivery of these campaigns were not similar, so it is hard to draw conclusions about the effectiveness of this education.

Education topics and intensity for people with early-stage type 1 diabetes and their families should be based on type 1 diabetes stage, age, rate of progression, etc. First-degree relatives may have different needs for support and guidance from the general population, as they have an established awareness of the implications and impact of IAb + status. Education topics should be linked to specifically timed action plans and include the topics detailed below. Education can be tailored so it is uniquely appropriate for both stage 1 and stage 2 type 1 diabetes ( Table 1 ). Clinical practitioners with experience in early-stage type 1 diabetes should be involved in the later steps of education.

When Should Education Be Provided?

The needs for education are centered on the key moments in the life of the person with early-stage type 1 diabetes ( 119 ). These are at the point of a positive autoantibody screen, at diagnosis of each stage, when monitoring tasks are performed, and annually for review and maintenance. Education is also critical during life transitions and milestones and when care needs change.

Key Education Topics

Education and self-care behaviors for individuals at risk for or with early-stage diabetes ( Table 1 ) can be derived from the overall framework of self-management skills for diabetes and related conditions. These are described in the ADCES7 self-care behaviors ( 125 ). Those relevant for at-risk individuals or those with early-stage type 1 diabetes focus on understanding the implications of their single (at-risk) or multiple (early-stage type 1 diabetes) IAb + status and the benefits of regular monitoring. Symptom awareness and metabolic monitoring are important to reduce the risks of hospitalization for DKA. If other family members have type 1 diabetes, HCPs should not assume preexisting awareness and knowledge. The most current education should always be mandated.

Educational Topics of Highest Value for IAb + Individuals and Family Members

For an individual who has tested positive for one or more autoantibodies, a person-centered plan should be developed that is best suited to the IAb + person and their individual situation. Their family members should be included as part of the program of education. The topics that may have high value are likely to include the following: 1 ) understanding autoimmunity and the confirmation of single (at-risk) or multiple (early-stage type 1 diabetes) IAb + status; 2 ) definition of at-risk or early-stage type 1 diabetes; 3 ) risk perception (accurate risk perception is linked with staying engaged in monitoring and with DKA prevention [ 126 ]); 4 ) risks and benefits of individual participation in research studies; 5 ) awareness of hyperglycemia episodes for introducing insulin at the right time; 6 ) strategies for healthy coping; 7 ) symptom awareness and prevention of DKA; 8 ) glucose monitoring (SMBG, CGM), if clinically recommended; 9 ) healthy behaviors, including meal planning and physical activity; 10 ) risks and benefits of intervention therapies; 11 ) monitoring planning, with descriptions of laboratory tests and devices that may be used ( Table 5 ); and 12 ) treatment options and introduction to insulin therapy.

Where Should Education Be Provided?

Education should be widely accessible via a variety of modalities, across multiple media platforms and settings, and should be crafted with the specific audience’s learning needs in mind. For education aimed at HCPs, a key requirement is for professional associations in all regions to be aligned with the educational program and curriculum, preferably compatible with their educational platforms and with accreditation. For education aimed at people with pre-stage 3 type 1 diabetes, in-person options associated with clinical appointments or in-group sessions are important, and strong evidence supports DSMES delivery through virtual, telehealth, telephone, text messaging, and web-based/mobile phone applications (apps) ( 127–131 ).

Who Should Provide Education?

The competencies that must be addressed in education are outlined in Fig. 2 . There is a need for diabetes professional associations to endorse the educational goals, educational tools, and educational content, as described. Different groups of individuals, including HCPs, community members, and individuals in need of monitoring and their families (indicated in the pyramid sections in Fig. 2 ), should have the competencies described and participate as appropriate.

Expert Clinical Advice for Education of Single IAb + (At-Risk) and Multiple IAb + (Early-Stage Type 1 Diabetes) Individuals

Education is the responsibility of all health professionals involved in the monitoring and care of individuals with type 1 diabetes. [E]

People who are at risk or with early-stage type 1 diabetes may participate in monitoring education programs to reduce the rate of DKA at diagnosis ( 33 , 90 , 91 ). [B]

Education should be provided 1 ) at the point of a positive autoantibody screening; 2 ) at diagnosis of each stage; 3 ) annually for review and maintenance; and 4 ) during life transitions. [E]

Education should accompany the implementation of all monitoring plans; this includes home glucose testing and any monitoring devices. [E]

Education should be culturally, linguistically, and socioeconomically congruent. [E]

Education topics and intensity should be based on type 1 diabetes stage and risk of progression and include the risks and benefits of intervention therapies, when appropriate. [E]

Diabetes education should be accessible, engaging, and person centered. This includes consideration of the developmental, social, emotional, cultural, and linguistic needs of the individual and/or their family. [E]

What Is the Current Landscape Regarding Psychosocial Support for People With Type 1 Diabetes–Related Autoantibodies?

People who learn that they or a loved one have type 1 diabetes–related autoantibodies often experience significant stress ( 132 ). This is in part because events that are unpredictable, uncontrollable and threatening may be highly stressful. People who have islet autoantibody positivity, particularly those who have multiple islet autoantibody positivity, will very likely develop type 1 diabetes in the future. However, disease progression is impossible to predict precisely and having IAb + status does not mean imminent type 1 diabetes onset ( 133 , 134 ); stage 3 type 1 diabetes, with associated insulin administration and glycemic monitoring, could be months or even years away ( 17 ).

When learning they have type 1 diabetes–related autoantibodies, individuals of all ages and their family members can experience a range of emotional and behavioral reactions ( 135 , 136 ), including shock, grief, guilt, anger, depression, and anxiety. If time passes with no diagnosis of stage 3 type 1 diabetes, cognitions about type 1 diabetes may change and individuals may become convinced they will never get the disease or have reduced risk, despite evidence to the contrary ( 137 ). Parents often engage in behaviors in attempts to prevent type 1 diabetes when faced with the news that their child is at increased risk, even when not provided with recommendations to do so, though more recent data have shown that lower physical activity and meal plans with a higher glycemic index are associated with faster progression to type 1 diabetes ( 138–140 ). Meal-planning changes are most commonly reported, with extra monitoring at home (including blood glucose checking) being particularly common in families with someone who already has type 1 diabetes ( 141 , 142 ).

Research has documented the psychosocial impact of newborn screening ( 143 ) as well as genetic and islet autoantibody screening for type 1 diabetes ( 132 , 136 ). Failure to understand the screening and risk information presented is common. For example, more than a third of participating mothers and over half of participating fathers in the TEDDY study stated that their child was not at increased risk for type 1 diabetes, despite being clearly informed of their child’s increased genetic risk ( 137 ). To date, no data are available on how children screened positive for islet autoantibodies perceive or react to their risk.

Emotional distress in response to a positive islet autoantibody screen is also common. Many parents of children in the TEDDY study experienced anxiety after learning that their child was at increased risk for developing type 1 diabetes, with mothers reporting higher anxiety than fathers ( 132 ). Although anxiety decreased across time for parents of IAb + children who never developed additional autoantibodies, anxiety remained elevated in many parents of children with multiple autoantibodies for years after the child’s first IAb + test result. Mothers who experienced negative interpersonal life events and postpartum depression, but who were accurate about their child’s type 1 diabetes risk, were particularly vulnerable to heighted anxiety ( 144 ). In the Autoimmunity Screening for Kids (ASK) study, which conducted islet autoantibody screening in the general population, 74.4% of parents reported significant levels of anxiety about their child’s type 1 diabetes risk at the first follow-up visit; parents with lower educational attainment were more likely to exhibit higher levels of anxiety ( 145 ).

Around 40% of mothers and 20% of fathers in the Fr1da study reported clinically elevated symptoms of depression after learning that their child was at increased risk for type 1 diabetes compared with around 18% of mothers and fathers of children who were IAb − ( 24 ). Depressive symptoms declined across 1 year, with scores in mothers of IAb + children remaining slightly elevated compared with mothers of IAb − children; scores in fathers did not remain elevated.

Although both the ADA and ISPAD have published recommendations about the psychosocial care of individuals with stage 3 type 1 diabetes ( 146–148 ), these are limited to general principles for care of those with early-stage type 1 diabetes ( 149 ). Thus, there is an urgent need to provide guidance on psychosocial support for individuals with type 1 diabetes–related autoantibodies and their families.

We recognize regional differences in health care resources may limit mental health resources for care of people with diabetes. In most areas, there are insufficient mental and behavioral health professionals with expertise in the psychosocial aspects of type 1 diabetes who can provide the care recommended by the ADA and ISPAD ( 146–148 ).

What Is the Purpose of Psychosocial Support?

The overall goal of providing psychosocial support for individuals identified as having early-stage type 1 diabetes and their families is to assist them in successfully managing the psychosocial impacts associated with this life-changing news. To accomplish this goal, emotional, cognitive, and behavioral functioning need to be assessed and addressed not only in individuals with type 1 diabetes–related autoantibodies but in their family members as well, when appropriate.

What Type of Support Should Be Provided?

The essential first step is to ask the individual who is at risk for type 1 diabetes and/or their caregivers and family members about their reactions upon receiving the news that they have type 1 diabetes–related autoantibodies. However, asking once is not enough, as adjustment to autoantibody status may change over time ( 132 ). Inquiring about how individuals are coping with the news and their current needs should be conducted at every monitoring visit. Examples of questions to include in the conversation include:

How do you feel about this news?

Others have said this news brings feelings of sadness or worry, what are your feelings?

What is your understanding about having multiple autoantibodies?

What type of things are you doing to try to prevent type 1 diabetes?

What are your thoughts about talking with a counselor about your feelings from this news?

It is also important to consider developmental and family-specific factors when assessing psychosocial needs. For example, children and adolescents with type 1 diabetes autoantibodies may experience varied emotional, cognitive, and behavioral impacts as they develop. This further emphasizes the need for ongoing, regular assessment of psychosocial needs. Additionally, individuals with a family history of type 1 diabetes may react differently to learning about type 1 diabetes–related autoantibodies ( 141 ) compared with those who are unfamiliar with the disease; family context and prior experience with type 1 diabetes are important considerations when assessing psychosocial impact and the need for additional support.

Although increased anxiety and depression can occur in individuals with type 1 diabetes–related autoantibodies and their family members, this can be reduced by monitoring for the potential development of type 1 diabetes ( 120 ). Providing individuals with regular monitoring for type 1 diabetes, depending on stage, as outlined in earlier sections of this statement, can help individuals manage some of the unpredictability of type 1 diabetes development ( 120 , 132 ).

Based on the extant literature, diabetes-focused organizations, such as the ADA and ISPAD, have provided recommendations on the importance of individuals with diagnosed type 1 diabetes receiving psychosocial care ( 146–148 ) that is preferably integrated into routine diabetes visits and delivered by providers with diabetes-specific training ( 154 ). While the same level of evidence does not yet exist in those individuals with type 1 diabetes–related autoantibodies, the well-documented emotional, cognitive, and behavioral impacts of autoantibody status certainly suggest that a similar standard for psychosocial care should be available for all individuals who are at risk for developing type 1 diabetes and their families. For individuals with early-stage type 1 diabetes and their family members, there are well-developed models of managing psychosocial reactions to risk status, including age-specific education and assigned contact people to answer questions, who can also serve as role models ( 9 , 145 ).

Ideally, psychosocial care should be integrated with routine monitoring visits and delivered by HCPs using a collaborative, person-centered, culturally informed approach. When available, refer to mental and behavioral health professionals with expertise in type 1 diabetes for additional assessment and treatment. For individuals residing in the U.S., the ADA publishes the Mental Health Provider Directory, which lists providers with expertise in diabetes ( 153 ).

Expert Clinical Advice for Psychosocial Support for Single IAb + (At-Risk) and Multiple IAb + (Early-Stage Type 1 Diabetes) Individuals

Emotional, cognitive, and behavioral functioning should be assessed in people at risk or with early-stage type 1 diabetes and their family members, when appropriate. Anxiety, risk perception, and behavior changes should specifically be assessed. [E]

As an essential first step to providing psychosocial support, HCPs should ask the individual at risk or with early-stage type 1 diabetes and/or their caregivers and family members about their reactions upon receiving the news that they have type 1 diabetes–related autoantibodies. This can be accomplished using guiding questions and standardized and validated questionnaires. [E]

At each monitoring visit, there should be enquiries into current needs, particularly coping. [E]

Psychological care should be integrated into routine medical visits and, whenever possible, delivered by providers with diabetes-specific training. [E]

This consensus document for monitoring individuals with single (at-risk) and multiple (early-stage type 1 diabetes) islet autoantibody positivity covers key principles based on existing evidence and agreed expert opinion. It also highlights the significant unmet need for further research on early-stage type 1 diabetes to further increase the rigor for future guidance and recommendations, and drive the evolution of clinical care for people who have tested positive for islet autoantibodies. The key principles in this consensus document will be subject to updating once additional evidence becomes available, as indicated in Table 6 .

This article contains supplementary material online at https://doi.org/10.2337/figshare.25800055 .

This consensus report was endorsed by the European Society for the Study of Diabetes (EASD), American Diabetes Association (ADA), American Association of Clinical Endocrinology (AACE), American College of Diabetology (ACD), Association of Diabetes Care & Education Specialists (ADCES), Australian Diabetes Society (ADS), the International Society for Pediatric and Adolescent Diabetes (ISPAD), Advanced Technologies & Treatments for Diabetes (ATTD), DiaUnion, the Endocrine Society, and JDRF International.

This article is being simultaneously published in Diabetes Care ( https://doi.org/10.2337/dci24-0042 ) and Diabetologia ( https://doi.org/10.1007/s00125-024-06205-5 ) by the ADA and the EASD.

A consensus report is a document on a particular topic that is authored by a technical expert panel under the auspices of ADA. The document does not reflect the official ADA position but rather represents the panel’s collective analysis, evaluation, and expert opinion. The primary objective of a consensus report is to provide clarity and insight on a medical or scientific matter related to diabetes for which the evidence is contradictory, emerging, or incomplete. The report also aims to highlight evidence gaps and to propose avenues for future research. Consensus reports undergo a formal review process, including external peer review and review by the ADA Professional Practice Committee and ADA scientific team for publication.

This article is featured in a podcast available at diabetesjournals.org/care/pages/diabetes_care_on_air .

Acknowledgments. The author group thanks JDRF for organizing the initial expert conference and for providing funding to Robert Brines, Bite Medical Consulting (Cambridge, U.K.), who supported the author group by collating and compiling author feedback and revisions during the manuscript drafting process. The authors acknowledge the review and endorsement of the following organizations: Advanced Technologies & Treatments for Diabetes (ATTD), the American Association of Clinical Endocrinology (AACE), the American College of Diabetology (ACD), the American Diabetes Association (ADA), the Association of Diabetes Care & Education Specialists (ADCES), the Association for the Endocrine Society, the Australian Diabetes Society (ADS), DiaUnion, the European Association for the Study of Diabetes (EASD), the International Society for Pediatric and Adolescent Diabetes (ISPAD), and JDRF International.

Duality of Interest. M.P. has received honoraria for participation on advisory boards for AstraZeneca, Eli Lilly, MannKind Corp., Medtronic Diabetes, Pfizer, Sanofi, Dompé, LifeScan, Novo Nordisk, Insulet, Provention Bio, Merck, Ascensia Diabetes Care, Bayer, Embecta, and Tandem Diabetes Care and as a speaker for Eli Lilly, Medtronic Diabetes, Novo Nordisk, Pfizer, Sanofi, and Ascensia Diabetes Care. M.P. owns stocks of DreaMed Diabetes and NG Solutions, and his institution has received research grant support from Eli Lilly, Medtronic Diabetes, Novo Nordisk, Pfizer, Sanofi, DreaMed Diabetes, NG Solutions, Dompé, Lumos, GWave, OPKO, Provention Bio, and AstraZeneca, travel expenses from Medtronic Diabetes and Sanofi, and consulting fees from Qulab Medical and Provention Bio. T.B. served on advisory boards of Novo Nordisk, Sanofi, Eli Lilly, Boehringer Ingelheim, Medtronic, Abbott, and Indigo Diabetes. T.B. received honoraria for participating on the speakers bureau for Eli Lilly, Novo Nordisk, Medtronic, Abbott, Sanofi, Dexcom, Adventis, AstraZeneca, and Roche. T.B.’s institution has received research grant support and travel expenses from Abbott, Medtronic, Novo Nordisk, Sanofi, Novartis, Sandoz, and Zealand Pharma. R.E.J.B. has received consulting fees from Provention Bio. H.M.C. has received research grant support from IQVIA, JDRF, Chief Scientist Office, Diabetes UK, and the UK Medical Research Council (UKRI). H.M.C. has received honorarium from Novo Nordisk and owns shares in Roche Pharmaceuticals and Bayer AG. T.D. has received honoraria and speaker honoraria and consulting fees and his former institution has received research support from Abbott, AstraZeneca, Boehringer Ingelheim, Dexcom, Eli Lilly, Novo Nordisk, Provention Bio, Sanofi, and Vertex Pharmaceuticals. He is a shareholder in DreamMed, Ltd. K.D. has received honorarium for participation on advisory boards for Medtronic and Novo Nordisk and speaker fees from Abbott, Eli Lilly, Novo Nordisk, Medtronic, and Pfizer. O.E. has received research support from MannKind Corp., Medtronic Diabetes, Abbott, Dexcom, Eli Lilly Pharmaceuticals, Janssen Pharmaceuticals, and Vertex Pharmaceuticals. O.E. has also participated on advisory boards for Medtronic and Sanofi. O.E. has received consultation and speaker fees from Medtronic Diabetes, Sanofi, and Vertex. All financial support from industry for O.E. has been through his organization, T1D Exchange. R.A.G. has received honorarium from Lark, Sweetch, StartUp Health, Vida, and Valendo. C.J.G.'s institution received payment from Sanofi as a clinical trial center. K.J.G. has received sponsored travel from JDRF. W.H. received grant/consultancy fees from Sanofi/Provention Bio. M.J.H. has received grants or consultancy fees from Sanofi, MannKind Corp., and SAB Biotherapeutics and is a stock options holder of SAB Biotherapeutics. R.I.G.H. has received honoraria for speaking from EASD, Eli Lilly, ENCORE, Liberum, Novo Nordisk, Rovi, and Boehringer Ingelheim. R.I.G.H. has received conference funding from Novo Nordisk and Eli Lilly. O.K. has received honoraria and lecture fees from Sanofi, Dexcom, and Medtronic. R.W.L. has received a consultancy fee from Cigna Insurance. D.M.M. has received research support from the National Institutes of Health, JDRF, National Science Foundation, and the Leona M. and Harry B. Helmsley Charitable Trust, and his institution has had research support from Medtronic, Dexcom, Insulet, Bigfoot Biomedical, Tandem Diabetes Care, and Roche. C.M. serves or has served on advisory panels for Novo Nordisk, Sanofi, Eli Lilly and Company, Novartis, Boehringer Ingelheim, Roche, Medtronic, Imcyse, Insulet, Biomea Fusion, and Vertex Pharmaceuticals. Financial compensation for these activities has been received by KU Leuven; KU Leuven has received research support for C.M. from Medtronic, Imcyse, Novo Nordisk, Sanofi, and ActoBio Therapeutics. C.M. serves or has served on speakers bureaus for Novo Nordisk, Sanofi, Eli Lilly and Company, Medtronic, and Boehringer Ingelheim. Financial compensation for these activities has been received by KU Leuven. C.M. is president of EASD. All external support of EASD is to be found on www.easd.org . H.K.O.’D. received compensation from Sanofi for attending their advisory board and for speaking at ADA 84th Scientific Sessions. R.P.-B. has received payment or honoraria from Bayer, Lexicon Pharma, Novo Nordisk, Averitas Pharma, Nevro, Roche, and Medtronic. M.J.R. has received honoraria and grants from Sanofi. K.M.S. has received consultancy fees, grants, or honoraria from Provention Bio and Sanofi. E.K.S. has received consulting fees from Sanofi and DRI Healthcare and has received payment for lectures from Health Matters CME, Medscape, Med Learning Group LLC, and the ADA. J.S.S. has been a scientific advisory board member for 4Immune, ActoBiotics, Avotres, and Quell Therapeutics. J.S.S. has been a data safety board member for Imcyse and Provention Bio and is a member of the board of directors for SAB Therapeutics. J.S.S. has been an advisor or consultant for ImmunoMolecular Therapeutics, Novo Nordisk, Remedy Plan, Inc., SAB Therapeutics, and Sanofi. J.S.S. has shares in or is an option holder for 4Immune, Avotres, ImmunoMolecular Therapeutics, Remedy Plan, Inc., and SAB Therapeutics. C.S. has received research funding from Cour Pharmaceuticals and consultancy fees from Sanofi and GentiBio. L.A.D. has received research support to their institution from Dompé, Lilly, MannKind Corp., Medtronic, Provention/Sanofi, and Zealand and consulting fees from Vertex Pharmaceuticals and Abata. L.A.D. has a patent pending for difluoromethylornithine (DFMO). No other potential conflicts of interest relevant to this article were reported.

Author Contributions. All listed authors were responsible for drafting the consensus guidance article and reviewing it critically for important intellectual content. All authors approved the final draft version of the manuscript submitted for publication.

Prior Presentation. Parts of this work were presented at the 17th International Conference on Advanced Technologies & Treatments for Diabetes Conference, Florence, Italy, 6–9 March 2024, and at the ADA 84th Scientific Sessions, Orlando, FL, 21–24 June 2024.

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Diabetic ketoacidosis as first presentation of type 1 diabetes mellitus in a young child

Important differential diagnosis for respiratory distress.

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Diabetic ketoacidosis (DKA) is a life-threatening complication of hyperglycemia in patients with type 1 diabetes mellitus (T1DM). As a first presentation, overlapping signs of DKA and the respiratory infections that can trigger DKA, especially during cold and flu seasons, can complicate this diagnosis. Kussmaul breathing, characterized by tachypnea and increased depth of breath, is a classic sign of DKA; however, change in depth of breathing might not be apparent in younger children owing to their size. This case describes a toddler in respiratory distress, attending her primary care clinic with a 1-week history of upper respiratory tract symptoms. For family physicians, it is important to keep a differential diagnosis for respiratory distress in mind. If the examination is not consistent with more common presentations, then other causes should be considered.

A 22-month-old girl presented with her mother to the family doctor’s office for worsening dyspnea. Her mother described hearing a “barky” cough and reported symptoms consistent with a viral prodrome in the past week. She also had older siblings at home with upper respiratory tract infections. On examination she was tachypneic, using her accessory muscles to breathe, and was grunting. Auscultation of her chest revealed good air entry bilaterally with no adventitious sounds, and her oxygen saturation was normal. However, during the examination, despite receiving oxygen by facial mask and several doses of salbutamol, she became progressively lethargic. Therefore, emergency medical services transferred her to the emergency department with a provisional diagnosis of croup based on her initial clinical presentation and rapid clinical decline in the office. In the emergency department, results of bloodwork requested owing to her decreased level of consciousness revealed that she was profoundly hyperglycemic and she was treated according to the pediatric DKA protocol. She was admitted with a new diagnosis of T1DM and was referred for ongoing diabetes management.

• Differential diagnosis

There are many differential diagnoses for Kussmaul breathing. In the context of T1DM, Kussmaul breathing is the result of metabolic acidosis. A focused differential diagnosis pertinent to the pediatric population should consider disorders from other systems ( Box 1 ).

Differential diagnoses for Kussmaul breathing in young children

Heart failure

Cardiogenic shock

Respiratory

Infection—pneumonia, croup, bronchiolitis

Uncontrolled asthma

Upper airway obstruction (eg, foreign body)

Metabolic and endocrine

Acidosis—MUDPILES (methanol, uremia, diabetic ketoacidosis, propylene glycol, paraldehyde, iron, isoniazid, lactic acidosis, ethylene glycol, salicylate drugs [eg, alcohol, ingested poisons, acetylsalicylic acid])

Renal failure

Inborn errors of metabolism

Hyperthyroidism

Neurologic and psychological

Intracranial pathology with increased intracranial pressure (eg, space-occupying lesion, bleeding, cerebral edema)

Substantial head trauma

Type 1 diabetes mellitus is a common chronic condition in childhood. The age of onset for childhood T1DM has a bimodal distribution: one peak at 4 to 6 years of age and a second peak in early puberty (10 to 14 years of age). 1 In the United States, the incidence of T1DM in non-Hispanic white children is quoted to be 23.6 per 100 000 per year. 2 Among the provinces in Canada, incidence ranges from 36 per 100 000 in Newfoundland and Labrador 3 to 15 per 100 000 in Quebec. 4 A stressor (such as infection) on top of poor glycemic control can result in DKA.

The reported frequency of DKA as the first presentation of childhood T1DM ranges from 15% to 67% in various studies. 5 More meaningfully, more than half of children younger than 3 years of age present with DKA as their first presentation of T1DM. 5 Presenting symptoms of DKA include polyuria and polydipsia, weight loss, fatigue, altered mental status, and respiratory distress (ie, Kussmaul breathing). 6 While polyuria and polydipsia frequently occur, Kussmaul breathing occurs in only 28% of DKA presentations. 7 In addition to physiologic stressors, other risk factors for developing DKA include female sex, no family predisposition, African American race, a younger age (< 5 years old), and other social factors including low socioeconomic status, limited access to medical services, and unstable family circumstances. 5 , 8 , 9

A 2016 case study reported a 7-week-old infant with DKA presenting to the emergency department with fever, altered mental status, and respiratory distress. In this situation, the workup included a capillary blood glucose reading and investigations into sources of infection. 10 This case study is consistent with reports that a preceding febrile illness is observed in 40% of DKA cases. 6

Our young patient presented with a viral prodrome and previous symptoms consistent with croup; however, the physical examination findings did not match the medical history. This case highlights the need for family physicians to be vigilant when past symptoms and the clinical examination appear discordant. During cold and flu season, family physicians might be lured into making an early diagnosis of respiratory infection in patients presenting with respiratory symptoms. Important yet simple questions probing for polyuria and polydipsia should be asked in young children presenting with respiratory issues to help identify whether DKA is a diagnostic consideration. Finally, consider performing point-of-care capillary blood glucose testing in children presenting with symptoms of respiratory distress and reduced level of consciousness to assess for DKA. Ketones can also be measured through urine dips or point-of-care capillary devices to support the diagnosis.

Editor’s key points

▸ Diabetic ketoacidosis (DKA) is a common presentation of type 1 diabetes mellitus in children younger than 3 years of age.

▸ Kussmaul breathing, characterized by tachypnea and increased depth of breath in response to metabolic acidosis, is a less common first presentation of DKA.

▸ During cold and flu season, DKA can be harder to identify because Kussmaul breathing might be mistaken as a sign of respiratory infection.

▸ Assessing for polyuria and polydipsia and performing point-of-care glucose and ketone testing in young children presenting with respiratory symptoms could help family physicians consider DKA and type 1 diabetes mellitus as potential diagnoses.

Competing interests

None declared

This article is eligible for Mainpro+ certified Self-Learning credits. To earn credits, go to www.cfp.ca and click on the Mainpro+ link.

This article has been peer reviewed.

La traduction en français de cet article se trouve à www.cfp.ca dans la table des matières du numéro de juin 2020 à la page e180 .

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Diabetic Ketoacidosis: Clinical Characteristics and Precipitating Factors

Wajeeha shahid.

1 Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK

2 Internal Medicine, Dow University of Health Sciences, Karachi, PAK

Aamir Makda

Vinesh kumar.

3 Internal Medicine, Ghulam Muhammad Mahar Medical College, Sukkur, PAK

Sidra Memon

Amber rizwan.

4 Family Medicine, Jinnah Postgraduate Medical Center, Karachi, PAK

Introduction: Diabetic ketoacidosis (DKA) is a complication of hyperglycemia. Through this study we plan to study the clinical features of DKA and precipitating factors responsible for DKA in type 1 and type 2 diabetes.

Methods: This cross-sectional observational study was conducted in the emergency department of a tertiary care hospital in Sukkur, Pakistan from August 2019 to February 2020. Symptoms and precipitating factors were noted in a self-structured questionnaire.

Results: Out of 71 patients, 19 (26.7%) patients had type 1 diabetes mellitus and 52 (73.3%) patients had type 2 diabetes mellitus. The most common clinical symptom was nausea and vomiting (57.7%), followed by pain in abdomen (42.2%) and dehydration (42.2%). We found that the most common precipitating factors were infections (69.0%) and non-compliance to treatment (53.5%). Among various infections, people commonly presented with pneumonia (38.7%) and urinary tract infection (30.6%).

Conclusion: Diabetic ketoacidosis presents with vague symptoms such as nausea, vomiting, and pain in abdomen. Characteristic findings of DKA such as Kussmaul breathing was present in limited patients. Infections in diabetic patients should be carefully monitored as they are the most common precipitating factors for DKA.

Introduction

Diabetes mellitus (DM) is an endocrine disorder that leads to abnormal metabolism of blood glucose. It is a chronic disease that results in both short-term and long-term complications. Diabetes can lead to a number of complications such as hyperosmolar hyperglycemic state (HHS) and diabetic ketoacidosis (DKA) [ 1 ]. Due to hyperglycemic emergencies, the incidence of mortality ranges from 4% to 40% in developing countries [ 2 ].

DKA presents with vague symptoms such as nausea, vomiting, and abdominal pain. Other symptoms include increased thirst and urination. Kussmaul breathing (labored deep breathing) and fruity odor are specific signs present on examination of a patient with diabetic ketoacidosis [ 3 ]. Various precipitating factors of DKA are reported in studies, especially missed insulin dose and an ongoing infection [ 4 ]. Other precipitating factors include stressful events such as stroke, myocardial infarction, and trauma, as well as substance abuse [ 5 ]. The clinical outcome of DKA depends upon the patient’s response to initial medical intervention, the precipitating factor for DKA, and biochemical values. Factors such as advanced age, bedridden state, and the use of mechanical ventilator are independent predictors associated with 30-day mortality [ 4 ].

Diabetes and its complications are both very prevalent in Pakistan. However, there is minimal literature on symptoms, precipitating factors, and outcome of patients with DKA. This study aims to assess the trend of clinical features of DKA and its precipitating factors in diabetic patients. This study may assist clinicians in early recognition of DKA, leading to its timely management.

Materials and methods

This was a cross-sectional, observational study, conducted in the emergency department of a tertiary care hospital in rural Sindh, Pakistan. The study duration was August 2019 - February 2020 during which 71 participants were included in the study. Diagnostic criteria mentioned in the International Society for Paediatric and Adolescent Diabetes (ISPAD) Clinical Practice Consensus Guidelines 2018 were used as a reference for diagnosis and management of DKA [ 5 ]. According to guidelines, we diagnosed DKA through a triad of symptomatology and lab findings, i.e. hyperglycemia, ketosis, and acidemia (Figure ​ (Figure1 1 ).

Clinical presentation and precipitating risk factors were noted in a self-administrated questionnaire. Stress to body was considered as any recent cardiovascular event such as myocardial infarction or cerebrovascular event such as stroke. A blood sample was taken at the time of admission and sent to the laboratory for ketone levels and bicarbonates. Blood glucose level was checked using a glucometer. Data were processed and analyzed using IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, NY, USA). Mean and standard deviation (SD) were calculated for continuous variables. Frequency and percentages were calculated for categorical variables.

Out of 71 patients, 19 (26.7%) patients had type 1 diabetes mellitus and 52 (73.3%) had type 2 diabetes mellitus. Mean age of patients in this study was 52 ± 11 years. Mean age of participants for type 1 diabetes was 39 ± 6 years and for type 2 diabetes it was 58 ± 11 years. The mean duration of diabetes was 6 ± 2 years. There were 34 (47.8%) males and 37 (52.2%) females. The most common clinical symptoms were nausea and vomiting (57.7%), followed by pain in abdomen (42.2%) and dehydration (42.2%). Kussmaul breathing was present in 10 (14.0%) participants (Table ​ (Table1 1 ).

The most common precipitating factors in this study were infections (69.0%) and non-compliance to treatment (53.5%) (Table ​ (Table2 2 ).

Among various infections, pneumonia (38.7%) and urinary tract infections (30.6%) were most commonly reported (Table ​ (Table3 3 ).

Diabetic ketoacidosis is associated with reduced level of functional insulin in the body. This reduction in insulin levels leads to glucose overload, either due to increased consumption of glucose or by an increased level of counter-regulatory hormones which include catecholamines, cortisol, glucagon, and growth hormone. This imbalance results in increased glucose production by the liver with resistance in glucose utilization in the peripheral tissues [ 3 ]. Diabetic ketoacidosis also impairs metabolic processes causing increased gluconeogenesis, lipolysis, ketogenesis, and decreased glycolysis [ 5 ]. 

In our study, diabetic ketoacidosis was more prevalent in type 2 diabetes. The most common clinical presentation was nausea and vomiting, followed by abdominal pain. Seth et al. in 2015 also reported nausea, vomiting, and pain in abdomen as the most common clinical presentations in patients with DKA [ 3 ]. Severe vomiting and abdominal pain are reported as the most common symptoms in other studies as well [ 2 , 6 ]. Ongoing catabolism and acidosis in DKA patients can lead to extreme vomiting [ 7 ]. In this study, dehydration was present in 30% of the participants. Osmotic diuresis caused by glycosuria is mainly responsible for dehydration and electrolyte disturbance [ 7 ].

In our study, infection and non-compliance to treatment were major precipitating factors. This result is similar to other studies, which also reported infections and non-compliance as major precipitating factors [ 2 , 3 ]. These precipitating factors are particularly important as both infection and non-compliance are common in patients with diabetes. The greater incidence of infection in diabetic patients is due to numerous factors including damage to neutrophil function, impairment of humoral immune system, and neuropathies [ 8 ]. In developed countries, the rate of non-compliance in long-term diabetic patients is 50%. World Health Organization (WHO) predicts that the rate of non-compliance to diabetic treatment may be even higher in developing countries [ 9 ]. According to a study in Pakistan, 62% of the diabetic population is non-compliant to their treatment regime [ 10 ]. Various studies have identified other factors as well which are responsible for diabetic ketoacidosis. These factors include events such as myocardial infarction, pulmonary embolism, and pancreatitis as well as the use of alcohol and drugs [ 7 ].

In this study, pneumonia (38.7%) and urinary tract infection (30.6%) were the most common infections identified in patients with DKA. Seth et al. also reported that pneumonia and urinary tract infection were common in diabetic ketoacidosis patients [ 3 ]. Apart from these infections, patients also presented with tuberculosis, diabetic foot, and gastrointestinal tract infections. This was in accordance with previous studies, which showed that infection in any part of the body may result in diabetic ketoacidosis [ 11 , 12 ].

To the best of our knowledge, this is the first study from a rural area of Pakistan that has studied clinical presentation and precipitating factors of DKA. It will help clinicians identify high-risk patients for diabetic ketoacidosis and give them time to prepare for medical intervention and if needed, to prevent mortality. However, we are aware of the limitations of the study. Since it was carried out in an emergency department, after initial management patients were shifted to either ward or ICU and were not followed for outcome. The study was only conducted in one institute, hence we cannot generalise the results.

Diabetic ketoacidosis is not an infrequent complication of diabetic mellitus. The clinical presentation is vague. Symptoms that should raise suspicion regarding DKA include nausea, vomiting, abdominal pain, and dehydration. Appropriate diagnostic tests should be done for timely diagnosis of diabetic ketoacidosis.

Conclusions

In our study, diabetic ketoacidosis was more prevalent in type 2 diabetes. Patients commonly presented with nausea, vomiting, and abdominal pain. The most common precipitating factors were infections (such as pneumonia and urinary tract infections) and non-compliance to treatment. Awareness among diabetic patients and physicians regarding symptoms and precipitating factors of diabetic ketoacidosis is necessary, as it may assist in early diagnosis and timely treatment.

The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.

The authors have declared that no competing interests exist.

Human Ethics

Consent was obtained by all participants in this study. Ghulam Muhammad Mahar Medical College issued approval GMMMC/0619/3B

Animal Ethics

Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue.

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Perioperative management of patients with diabetes and cancer: challenges and opportunities.

Simple Summary

1. introduction, 2. methodology, 3. epidemiology, 4. classification of diabetes, 5. hyperglycemia caused by antineoplastic agents, 5.1. corticosteroids, 5.2. targeted therapies: pi3k/akt/mtor pathway, 5.3. immune checkpoint inhibitors, 6. operative complications in diabetes, 6.1. cardiovascular disease, 6.2. nephropathy, 6.3. neuropathy, 6.4. infection and surgical wound complications, 7. perioperative management of patients with diabetes and cancer, 7.1. preoperative optimization, 7.2. perioperative management of blood glucose, 7.3. perioperative management of oral and non-insulin-injectable diabetes medication, 7.4. perioperative management of insulin, 7.5. postoperative management, 8. future directions, author contributions, conflicts of interest.

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Shouman, M.; Brabant, M.; Rehman, N.; Ahmed, S.; Shahid, R.K. Perioperative Management of Patients with Diabetes and Cancer: Challenges and Opportunities. Cancers 2024 , 16 , 2821. https://doi.org/10.3390/cancers16162821

Shouman M, Brabant M, Rehman N, Ahmed S, Shahid RK. Perioperative Management of Patients with Diabetes and Cancer: Challenges and Opportunities. Cancers . 2024; 16(16):2821. https://doi.org/10.3390/cancers16162821

Shouman, Mohamed, Michelle Brabant, Noor Rehman, Shahid Ahmed, and Rabia K. Shahid. 2024. "Perioperative Management of Patients with Diabetes and Cancer: Challenges and Opportunities" Cancers 16, no. 16: 2821. https://doi.org/10.3390/cancers16162821

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Psychiatric Disturbances In Type 1 Diabetes: An Overview

Diabetics' mental health has been proven to be associated with depression, anxiety, and schizophrenia.

Dr. Ayushi Yogendra Singh

Medically reviewed by

Dr. Vishal Anilkumar Gandhi

Introduction :

Diabetes and mental health treatments have long piqued the curiosity of endocrinologists and psychiatrists. Thomas Willis contended in the 17th century that "lasting melancholy and various depressions " were the root cause of diabetes. Insulin was being utilized in a psychiatric treatment called insulin coma therapy within ten years of its discovery. This relationship has only garnered significant scientific attention in the last few decades. Mental health problems and diabetes are mutually reinforcing, with each affecting the other in unique ways. This article covers a number of the characteristics of this link. For instance, it has been shown that alcohol and tobacco affect the pharmacokinetics of oral hypoglycemic medications.

What Are the Patterns of Diabetes and Mental Health Issues Co-occurring?

Diabetes and psychological illnesses can coexist in a variety of ways. First, there is a chance that the two will manifest as separate states with no obvious relationship. Both are the results of separate and concurrent pathogenic pathways in such a case. Second, the development of psychological illnesses may aggravate the course of diabetes. In these situations, diabetes plays a role in the etiology of mental illnesses. In such a setting, a variety of biological and psychological elements mediate the onset of psychiatric diseases. Third, several mental illnesses, including schizophrenia and depression, are important independent risk factors for the onset of diabetes. Fourth, there may be similarities between illnesses like panic attacks and the clinical presentation of episodes of hypoglycemia and ketoacidosis.

There are further interactions between diabetes and mental health issues. Some substances of abuse, like alcohol and tobacco, can change the pharmacokinetics of oral hypoglycemic medications. Furthermore, comorbid mental health conditions like depression may make it more difficult to control diabetes by affecting treatment compliance. Analogously, some disorders including needle and injection phobia may make it difficult to conduct some tests and administer certain treatments, like insulin injections and blood glucose tests. Additionally, those with psychiatric illnesses are less likely to go for care. Delays of this kind would also delay the identification of co-occurring diabetes.

What Are the Consequences of Diabetes and Mental Illnesses Coexisting?

Patients with diabetes who also have co-occurring psychiatric disorders are more likely to have poorer quality of life, higher healthcare costs, poor treatment adherence, and poor glycaemic control (as indicated by elevated HbA1c levels). They may also experience more frequent ER visits due to diabetic ketoacidosis, more hospital admissions, and a higher dropout rate. Medical care is becoming more expensive as well. When co-occurring psychiatric illnesses and endocrine problems are present in a patient, the cost of care for non-mental health diseases is twice as high as it is in the non-cooccurring population, depending on the exact treatment environment.

What Is the Diagnosis of Mental Health Issues in Diabetes Patients?

Low rates of detection are one of the most management problems for people with diabetes who have psychological issues. Among patients receiving diabetic treatment , up to 45 percent of cases of severe psychological anguish and mental disorders go undiagnosed. Both patient- and physician-related factors contribute to this. Medical professionals need to be aware of the potential co-morbid mental illnesses that are linked to diabetes . Diabetes patients frequently experience psychiatric co-morbidity, as the parts that follow will emphasize. As a result, these people ought to undergo routine screenings for common mental illnesses. Short screening methods, including the symptom checklist-90 (SCL-90) and the patient health questionnaire (PHQ), are sensitive, time-efficient, and well-validated for diagnosing common psychiatric illnesses like anxiety and depression. To measure the degree of anxiety and depression in this population, measures like the Hospital Anxiety and Depression Scale (HADS) could be employed. Screening for the emergence of psychological illnesses in individuals with diabetes is crucial, and vice versa. It is essential to search for the behavioral and cognitive symptoms of psychiatric disorders because there may be some overlap between the physical characteristics of diabetes and mental illnesses.

1. Dizziness

Diabetes-related delirium may be a symptom of diabetic ketoacidosis or hypoglycemic episodes. The end of the range of clinical manifestations of these phases is represented by delirium. Hypoglycemic delirium is more common in diabetic patients with co-occurring psychological problems. Based on current nosological systems, it is challenging to quantify the precise prevalence of delirium in diabetes due to the usage of overlapping terms in the literature.

2. Substance Misuse:

• Cigarettes - There are two ways to consume tobacco: smokeless (gutkha, tobacco powder, khaini, snuff) and smoking (cigarettes, biri, hooka, cigars). Studies from Western settings have indicated that the prevalence of smoking among persons with diabetes is similar to that of the general population.
• Tobacco : Estimates of the percentage of patients with diabetes who drink alcohol range from 50 to 60 percent, according to epidemiological studies and populations undergoing treatment. There is constant discussion about drinking and the risk of diabetes. Moderate intake is defined as one drink for women and two for males per day. A single drink can be as little as 12 fluid ounces (355 milliliters) of beer or five fluid ounces (148 milliliters) of wine, both of which have been demonstrated to be healthful, although excessive intake is linked to an elevated risk of type 2 diabetes.

3. Mood Disorders

Conditions such as sadness, mania, and hypomania are classified as mood disorders. Numerous clinical and epidemiological studies have discovered a link between mental health problems and diabetes. Increased mortality and morbidity have been linked to this combination. A recent study found that compared to the general population, diabetic patients had a 50 to 100 percent increased incidence of depression. Studies conducted in hospitals and epidemiological surveys have revealed that the prevalence of diabetes in people with bipolar disorder is either the same or higher than in the general population.

Persons with diabetes are far more prone to suffer from anxiety problems than persons in general. Studies have revealed that anxiety problems and the symptoms they cause are powerful, independent indicators of the development of diabetes.

5. Psychosis and Other Psychotic Disorders

Psychosis is among the many medical disorders that diabetes is closely linked to. People with a diagnosis of schizophrenia have a higher chance of developing type 2 diabetes than people with other disorders. Individuals with a family history of schizophrenia, including first cousins, have a significantly increased risk of type 2 diabetes.

Conclusion :

A rising public health concern is diabetes. A lot of diabetics have trouble controlling their diabetes, frequently as a result of psychological problems, social problems, or mental diseases. Diabetes has major negative effects on the person and can cause blindness, kidney failure, and even amputations if left untreated. The rising number of hospitalizations and presentations to emergency rooms with problems connected to diabetes has an impact on healthcare services. Significant long-term expenses are linked to problems, including amputation and renal failure. Reducing the psychological and mental obstacles to effective glucose regulation can lessen the toll that diabetes and its complications have on both individuals and society as a whole.

Relation Between Diabetes and Psychiatric Disorders

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699801/

Diabetes and psychiatric disorders

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3193776/

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