Diabetes Mellitus Type 1

Background

• Diabetes mellitus type 1 is an endocrine disorder characterized by insulin deficiency usually due to autoimmune pancreatic beta-cell destruction, and resulting in hyperglycemia and complications such as ketoacidosis, cardiovascular disease, nephropathy, and retinopathy.
• Type 1 diabetes can occur at any age, but commonly presents in childhood or adolescence, often with classic symptoms such as polyuria, polydipsia, polyphagia, and sudden weight loss; about 30% of children and adolescents present in diabetic ketoacidosis (DKA), a metabolic emergency.
• Patients with type 1 diabetes are at increased risk for a number of other immune-mediated disorders, especially autoimmune thyroid disease and celiac disease.
• Teplizumab (Tzield) is a CD3-directed antibody FDA approved to delay onset of Stage 3 type 1 diabetes in patients ≥ 8 years old with Stage 2 type 1 diabetes.

Evaluation

• Perform blood testing to diagnose diabetes (Strong recommendation).
  • Diagnostic criteria for diabetes is any of the following:
    • fasting plasma glucose ≥ 126 mg/dL (7 mmol/L) (after no caloric intake for ≥ 8 hours)
    • symptoms of hyperglycemia with random plasma glucose ≥ 200 mg/dL (11.1 mmol/L)
    • 2-hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during a 75-g oral glucose tolerance test
    • HbA1c ≥ 6.5% (HbA1c may not be accurate for diagnosis in cases of pregnancy, hemoglobinopathy, certain anemias, or abnormal erythrocyte loss or replacement)
  • Repeat testing for confirmation in the absence of unequivocal hyperglycemia.
• If diabetic ketoacidosis is suspected, also measure electrolytes, blood urea nitrogen (BUN), creatinine, arterial blood gas, and serum and urine ketones. Urine ketones can be used when serum ketones are not available, but they are reported to have lower sensitivity and specificity compared to serum ketones.
• If clinical findings alone are insufficient to differentiate between type 1 and type 2 diabetes, consider blood tests for autoantibodies and C-peptide (Weak recommendation). Results consistent with a diagnosis of type 1 diabetes include:
  • autoantibodies to glutamic acid decarboxylase, islet cells, insulin, protein tyrosine phosphatase (ICA512 or IA2A), or zinc transporter protein (ZnT8)
  • low or undetectable C-peptide levels
• Consider additional testing at or soon after diagnosis with type 1 diabetes including:
  • a lipid profile (Weak recommendation)
  • screening for autoimmune thyroid disease (Weak recommendation)
  • screening for celiac disease in adults with suggestive signs, symptoms, or laboratory parameters (Weak recommendation)
• At least annually, assess urinary albumin (such as spot urinary albumin-to-creatinine ratio) and estimated glomerular filtration rate (GFR) in patients with type 1 diabetes beginning at 5 years after diagnosis (Strong recommendation) to screen for chronic kidney disease.

Management

• All patients with type 1 diabetes require insulin. For most patients, prescribe multiple daily insulin injections (1-2 injections of basal insulin and ≥ 3 injections/day of prandial insulin) or continuous subcutaneous insulin infusion (CSII) (insulin pump) (Strong recommendation).
• Consider individualized glycemic goals. Generally recommended targets in type 1 diabetes are (Weak recommendation):
  • HbA1c < 7% in most nonpregnant adults, < 6% in pregnant women, and < 7% across all pediatric age groups
  • in nonpregnant adults, preprandial plasma glucose of 80-130 mg/dL (4.4-7.2 mmol/L) and peak postprandial glucose < 180 mg/dL (10 mmol/L)
  • in pregnancy, fasting glucose < 95 mg/dL (5.3 mmol/L), and either:
    • 1-hour postprandial glucose < 140 mg/dL (7.8 mmol/L)
    • 2-hour postprandial glucose < 120 mg/dL (6.7 mmol/L)
• Provide support for diabetes self-management education (DSME), including nutritional management (Strong recommendation).
• Other medications:
  • Consider the addition of pramlintide to improve glycemic control in adults with type 1 diabetes failing to achieve glycemic goals on insulin alone (Weak recommendation).
  • Statins are the medication of choice for lowering low-density lipoprotein cholesterol (Strong recommendation).
    • Prescribe a statin for most adults > 40 years old with diabetes (Strong recommendation), and consider prescribing a statin if the patient is < 40 years old with cardiovascular risk factors (Weak recommendation).
    • Consider prescribing a statin for children > 10 years old with type 1 diabetes and low-density lipoprotein cholesterol > 160 mg/dL (4.1 mmol/L), or low-density lipoprotein cholesterol > 130 mg/dL (3.4 mmol/L) with ≥ 1 additional cardiovascular risk factor (Weak recommendation).
    • For patients of childbearing age, reproductive counseling is suggested prior to initiating a statin due to potential teratogenic effects.
  • Offer an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) in nonpregnant patients with hypertension or albuminuria (Strong recommendation).
  • Consider aspirin 75-162 mg/day for patients with increased cardiovascular risk, after a comprehensive discussion with the patient and if benefits are deemed to outweigh the risk of bleeding (Weak recommendation).
• For treatment of hypoglycemia:
  • Give glucose 15-20 g (or any carbohydrate that contains glucose) orally to a conscious individual, or glucagon if the patient is unconscious or unable to take glucose orally (Strong recommendation).
  • Prescribe glucagon to all patients at risk for level 2 or 3 hypoglycemia and instruct caregivers, school personnel, or family members on its use (Strong recommendation).
    • Level 2 hypoglycemia is defined as blood glucose < 54 mg/dL (3 mmol/L), the threshold at which neuroglycopenic symptoms arise and require immediate intervention to resolve.
    • Level 3 hypoglycemia is defined as a severe event characterized by altered mental status and/or physical functioning requiring assistance from another person to recover.
• Provide follow-up monitoring, including (Strong recommendation):

Table 1. Quarterly and Annual Follow-up Monitoring