Diabetes Mellitus Type 2 in Children and Adolescents

Background

• Diabetes mellitus type 2 is an endocrine disorder characterized by variable degrees of insulin resistance and deficiency, resulting hyperglycemia and complications such as cardiovascular disease, nephropathy, and retinopathy.
• Type 2 diabetes may be asymptomatic or may present with symptoms typical of hyperglycemia such as polyuria, polydipsia, and polyphagia.
• Previously, type 2 diabetes was uncommon in children, but prevalence is increasing, likely due to increasing childhood obesity; consider targeted screening of children with overweight or obesity and additional familial, demographic, or clinical risk factors (such as acanthosis nigricans, hypertension, dyslipidemia, or polycystic ovary syndrome) (Weak recommendation).

Evaluation

• Perform blood testing to diagnose diabetes (Strong recommendation).
  • Diagnostic criteria for diabetes is any of:
    • random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) with symptoms of hyperglycemia (such as, polyuria or polydipsia) or hyperglycemic crisis
    • no unequivocal hyperglycemia, but 2 abnormal test results from either 2 separate test samples or same sample; abnormal test results include
      • fasting plasma glucose ≥ 126 mg/dL (7 mmol/L) (no caloric intake for ≥ 8 hours)
      • 2-hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during 75-g oral glucose tolerance test
      • HbA1c ≥ 6.5% (48 mmol/mol) (HbA1c may not be accurate for diagnosis with pregnancy, hemoglobinopathy, certain anemias, or abnormal erythrocyte loss or replacement)
• If the patient presents with blood glucose ≥ 600 mg/dL (33.3 mmol/L), assess for hyperglycemic hyperosmolar nonketotic syndrome (Strong recommendation).
• If the child or adolescent has overweight or obesity and is being considered for the diagnosis of type 2 diabetes, test for pancreatic autoantibodies to exclude the possibility of type 1 diabetes (Strong recommendation).
• For female adolescents with type 2 diabetes, evaluate for polycystic ovary syndrome and perform laboratory tests when indicated (Strong recommendation).
• Perform genetic testing for neonatal diabetes in all children who are diagnosed with diabetes in the first 6 months of life (Strong recommendation).
• Additional testing for diabetic complications includes:
  • lipid profile - obtain fasting lipid profile after initial glycemic control has been established and annually thereafter (Strong recommendation)
  • estimated glomerular filtration rate at diagnosis and annually thereafter (Strong recommendation)
  • alanine aminotransferase and aspartate aminotransferase at diagnosis and annually thereafter (Strong recommendation)
  • urine albumin-to-creatinine ratio at diagnosis and annually to test for albuminuria (Strong recommendation)
  • performing dilated fundoscopy or retinal photography at diagnosis (Strong recommendation) and
    • annually (Strong recommendation)
    • every 2 years, for patients with adequately controlled glycemia and normal eye exam (Strong recommendation)
  • if obstructive sleep apnea suspected, refer to pediatric sleep specialist for polysomnogram (Strong recommendation)
• In children and adolescents with nephropathy, annual assessments of estimated glomerular filtration rate, serum potassium, and urinary albumin-to-creatinine ratio might aid in evaluating adherence and disease progression (Weak recommendation).
• For patients taking metformin, consider periodically assessing B12 levels since long-term use of metformin might be associated with B12 deficiency (Weak recommendation).

Management

• Individualize glycemic goals (Strong recommendation)
  • HbA1c treatment targets
    • for most children and adolescents with type 2 diabetes treated with oral medications alone, consider HbA1c target < 7% (53 mmol/mol) (Weak recommendation)
    • for children and adolescents with type 2 diabetes who have lesser degrees of beta-cell dysfunction, have had diabetes for a shorter period of time, or patients treated with lifestyle or metformin who lost a significant amount of weight, a more stringent HbA1c target such as HbA1c < 6.5% (48 mmol/mol) might be more appropriate if more stringent target can be achieved without significant hypoglycemia (Weak recommendation)
    • for children and adolescents with increased risk of hypoglycemia (reported relative low rate), less stringent HbA1c goals such as 7.5% (58 mmol/mol) may be appropriate (Weak recommendation)
    • for patients on insulin, HbA1c targets should be individualized and account for relatively low rates of hypoglycemia in children and adolescents with type 2 diabetes (Strong recommendation)
    • Measure HbA1c every 3 months (Strong recommendation).
• Consider individualized lipid and blood pressure goals; generally recommended targets in children with type 2 diabetes include:
  • lipid goals
    • low-density lipoprotein cholesterol < 100 mg/dL (2.6 mmol/L) (Weak recommendation)
    • high-density lipoprotein cholesterol > 35 mg/dL (0.905 mmol/L) (Weak recommendation)
    • triglycerides < 150 mg/dL (1.7 mmol/L) (Weak recommendation)
  • blood pressure consistently < 90th percentile for age, sex, and height (Weak recommendation)
• Provide support for dietary management, maintaining physical activity, and diabetes self-management education (Strong recommendation).
• Prescribe glucose-lowering medications (Strong recommendation).
  • Metformin is the first-line drug of choice for children and adolescents with type 2 diabetes with HbA1c < 8.5% (69 mmol/mol) to ≤ 9% (75 mmol/mol) (depending on organization) (Strong recommendation).
  • Dosing of metformin:
    • Start with 500-1,000 mg daily with food for 7 days.
    • Increase by 500 mg every 1-2 weeks as tolerated, up to 1 g twice daily of standard preparation, or 2 g once daily of extended-release metformin (maximum dose 2 g/day).
  • Insulin is the first medication of choice in children and adolescents with:
    • blood glucose ≥ 250 mg/dL (13.9 mmol/L) (Strong recommendation)
    • HbA1c ≥ 8.5% (69 mmol/mol) to > 9% (75 mmol/mol) (depending on organization) (Strong recommendation)
    • ketoacidosis or ketosis; initiate treatment with intravenous or subcutaneous insulin to rapidly correct metabolic derangements and hyperglycemia (Strong recommendation)
    • unclear distinction between type 1 diabetes and type 2 diabetes (Strong recommendation
• Initiate pharmacologic therapy in addition to lifestyle modification in children with diabetes if blood pressure consistently ≥ 95th percentile for age, sex, and height, or in adolescents aged ≥ 13 years with blood pressure ≥ 130/80 mm Hg. (Strong recommendation)
  • Options include angiotensin converting enzyme inhibitors or angiotensin receptor blockers for initial pharmacologic management (after appropriate reproductive counseling and implementation of effective birth control due to potential teratogenic effects) (Weak recommendation).
• For diabetes and hypertension in patients who are not pregnant, choose angiotensin converting enzyme inhibitors or angiotensin receptor blockers if any of
  • urinary albumin-to-creatinine ratio is modestly elevated (30-299 mg/g creatinine), suggest ACE inhibitor or ARB (Strong recommendation)
  • estimated glomerular filtration rate < 60 mL/min/1.73 m² and/or urinary albumin-to-creatinine ratio > 300 mg/g creatinine, strongly suggest ACE inhibitor or ARB (Strong recommendation)
• Choose lipid-lowering agents:
  • For youth with type 2 diabetes with low-density lipoprotein cholesterol remaining above goal (> 130 mg/dL) despite 6 months of dietary intervention, initiate statin therapy, with goal of low-density lipoprotein < 100 mg/dL (2.6 mmol/L) (Strong recommendation).
  • For youth with fasting triglycerides > 400 mg/dL (4.7 mmol/L) or nonfasting triglycerides > 1,000 mg/dL (11.6 mmol/L), optimize glycemia and initiate fibrate, with goal of fasting triglycerides < 400 mg/dL (4.7 mmol/L) to reduce risk of pancreatitis (Strong recommendation).