What is the appropriate evaluation and management of hyperglycemia in a young patient, including assessment for diabetic ketoacidosis and treatment options?

Management of Hyperglycemia in Young Patients

Initial Assessment and Risk Stratification

The approach to hyperglycemia in youth depends critically on the degree of metabolic decompensation at presentation, with treatment algorithms stratified by A1C level, presence of acidosis, and symptom severity. 1

Immediate Evaluation Required

• Check for diabetic ketoacidosis (DKA): Assess for symptoms (nausea, vomiting, abdominal pain, altered mental status), measure urine or serum ketones, and obtain arterial blood gas to evaluate for metabolic acidosis 1
• Assess for hyperglycemic hyperosmolar state (HHS): In patients with blood glucose ≥600 mg/dL, calculate serum osmolality, evaluate mental status changes, and assess degree of dehydration 1, 2
• Measure A1C if not recently obtained to determine chronic glycemic control 1
• Evaluate precipitating factors: Infection, medication non-adherence, acute illness, or dietary indiscretion 2, 3
• Assess renal function before initiating metformin therapy 1

Critical Clinical Distinction

• Diabetes type is often uncertain initially in youth with obesity due to overlapping presentations, with a substantial percentage of youth with type 2 diabetes presenting with clinically significant ketoacidosis 1
• Initial therapy should address hyperglycemia and metabolic derangements irrespective of ultimate diabetes type, with adjustment once metabolic compensation is established and pancreatic autoantibody results become available 1

Treatment Algorithm Based on Presentation

Scenario 1: DKA or Ketoacidosis Present

Initiate subcutaneous or intravenous insulin immediately to rapidly correct hyperglycemia and metabolic derangement. 1

• Use IV insulin infusion at 0.1 units/kg/hour after excluding hypokalemia (K+ <3.3 mEq/L) 2
• Aggressive fluid resuscitation: Start with 0.9% NaCl at 15-20 mL/kg/hour in the first hour 2
• Monitor blood glucose hourly and electrolytes every 2-4 hours during acute phase 2
• Once acidosis resolves, initiate metformin while continuing subcutaneous insulin therapy 1
• Transition to subcutaneous insulin when patient is stable with blood glucose <300 mg/dL and able to eat 2

Scenario 2: Marked Hyperglycemia Without Acidosis (A1C ≥8.5% or Blood Glucose ≥250 mg/dL)

Youth with symptomatic marked hyperglycemia (polyuria, polydipsia, nocturia, weight loss) should be treated initially with long-acting insulin while metformin is initiated and titrated. 1

• Start long-acting insulin at 0.5 units/kg/day, administered once daily (typically at bedtime) 1, 4
• Titrate insulin every 2-3 days based on fasting blood glucose monitoring, targeting 80-130 mg/dL 1, 4
• Simultaneously initiate metformin at 500 mg twice daily with meals if renal function is normal (eGFR >30 mL/min) 4
• Titrate metformin up to 2,000 mg per day (1,000 mg twice daily) as tolerated over 1-2 weeks to minimize gastrointestinal side effects 1, 4

Scenario 3: Metabolically Stable Diabetes (A1C <8.5% and Asymptomatic)

Metformin is the initial pharmacologic treatment of choice if renal function is normal. 1

• Start metformin at 500 mg twice daily with meals 4
• Titrate to 2,000 mg per day as tolerated 1
• Combine with lifestyle management and diabetes self-management education from diagnosis 1

Multidisciplinary Team Approach

A multidisciplinary diabetes team is essential, including a physician, diabetes care and education specialist, registered dietitian nutritionist, and psychologist or social worker 1

• Address comorbidities including obesity, dyslipidemia, hypertension, and microvascular complications from the outset 1
• Implement family-centered lifestyle modifications: Focus on healthy eating patterns emphasizing nutrient-dense, high-quality foods and decreased consumption of calorie-dense, nutrient-poor foods, particularly sugar-added beverages 1
• Encourage physical activity: At least 30-60 minutes of moderate-to-vigorous activity at least 5 days per week, with strength training on at least 3 days per week 1

Escalation Strategy When Glycemic Goals Not Met

Adding Non-Insulin Agents

If glycemic targets are no longer met with metformin (with or without long-acting insulin), GLP-1 receptor agonist therapy and/or empagliflozin should be considered in children 10 years of age or older. 1

• GLP-1 receptor agonists (such as liraglutide) are approved for youth ≥10 years if no personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 1
• SGLT2 inhibitor (empagliflozin) is now approved for youth with type 2 diabetes ≥10 years 1
• Consider maximizing noninsulin therapies (metformin, GLP-1 receptor agonist, and empagliflozin) before initiating or intensifying insulin therapy to minimize weight gain 1

Intensifying Insulin Therapy

For youth not meeting glycemic goals on basal insulin alone, add prandial insulin with a basal-bolus regimen. 1

• Initiate rapid-acting insulin (such as lispro or aspart) before each main meal at 4-6 units per meal, or calculate as 50% of total daily insulin dose divided among three meals 4
• Total daily insulin dose may exceed 1 unit/kg/day in youth with type 2 diabetes 1
• Insulin pump therapy may be considered for those on long-term multiple daily injections who are able to safely manage the device 1

Insulin Tapering Strategy

In youth initially treated with insulin and metformin who are meeting glucose goals, insulin can be tapered over 2-6 weeks by decreasing the insulin dose 10-30% every few days. 1

• Monitor glucose closely during tapering to ensure control is maintained 4
• Continue metformin (and other non-insulin agents if added) during and after insulin taper 1

Glycemic Targets

Target A1C <6.5% in youth with type 2 diabetes, which is lower than the <7% recommended for type 1 diabetes 1

• This more stringent target is justified by lower risk of hypoglycemia and higher risk of complications in youth-onset type 2 diabetes compared to type 1 diabetes 1
• Fasting blood glucose target: 80-130 mg/dL 4
• Monitor A1C every 3 months to assess glycemic control 4

Critical Pitfalls to Avoid

• Do not delay insulin therapy in patients with marked hyperglycemia (blood glucose ≥250 mg/dL or A1C ≥8.5%) who are symptomatic 1
• Do not use medications not FDA-approved for youth with type 2 diabetes outside of research trials 1
• Do not prematurely terminate IV insulin in DKA before acidosis is fully resolved 5
• Do not discontinue IV insulin before adequate subcutaneous insulin dosing is established 5
• Avoid SGLT2 inhibitors in patients with recurrent genitourinary infections or at risk for ketoacidosis 6
• Do not allow prolonged hyperglycemia at levels approaching 300 mg/dL to persist for months, as this increases risk of irreversible complications 6

Monitoring Requirements

• Blood glucose monitoring: Fasting glucose daily and pre-meal/2-hour post-meal glucose at least 3-4 times daily initially 4
• A1C measurement every 3 months until goals achieved, then at least twice yearly 4
• During DKA treatment: Blood glucose hourly, electrolytes and renal function every 2-4 hours 2
• Watch for cerebral edema if glucose falls too rapidly during DKA treatment 2