What dose of long‑acting insulin should be started in a 114‑kg severely obese young male with ketonuria and an A1c of 8.4%?

Initial Basal Insulin Dosing for a 114-kg Severely Obese Young Male with Ketonuria and HbA1c 8.4%

Start basal insulin immediately at 57 units once daily (0.5 units/kg/day) because ketonuria signals metabolic decompensation requiring insulin regardless of the HbA1c being below 8.5%. 1

Immediate Management Algorithm

Step 1: Rule Out Diabetic Ketoacidosis

• Obtain serum pH, bicarbonate, anion gap, and β-hydroxybutyrate to distinguish frank DKA from isolated ketonuria 1
• If DKA is present (pH < 7.3, bicarbonate < 15 mmol/L), initiate IV insulin infusion until acidosis resolves, then transition to subcutaneous insulin 1
• Check for severe hyperglycemia (glucose ≥ 600 mg/dL) to exclude hyperglycemic hyperosmolar syndrome 1

Step 2: Determine Diabetes Type

• Measure pancreatic autoantibodies (GAD, IA-2, ZnT8) immediately—obesity does not exclude type 1 diabetes 1
• If autoantibodies are positive: Continue multiple-daily-injection insulin or pump therapy and discontinue metformin 1
• If autoantibodies are negative: Maintain dual therapy with insulin plus metformin 1

Step 3: Initiate Insulin Therapy

• Starting dose: 57 units basal insulin (glargine or detemir) once daily at bedtime (0.5 units/kg × 114 kg) 2, 1
• This dose is appropriate because ketonuria mandates insulin initiation at 0.5 units/kg/day regardless of HbA1c 1
• Administer at the same time each day, preferably 20:00 h (8 PM) 2

Step 4: Start Metformin Concurrently

• Begin metformin immediately—do not wait for ketosis to resolve 1
• Titrate to 2000 mg daily (1000 mg twice daily with meals) as tolerated 2, 1
• Metformin reduces total insulin requirements by 20–30% and is the cornerstone of type 2 diabetes therapy in youth 2, 1

Titration Protocol

Basal Insulin Adjustment

• Increase by 4 units every 2–3 days if fasting glucose ≥ 180 mg/dL 2, 1
• Increase by 2 units every 2–3 days if fasting glucose 140–179 mg/dL 2
• Target fasting glucose: 80–130 mg/dL 2
• If hypoglycemia occurs (glucose < 70 mg/dL): Reduce dose by 10–20% immediately 2

Critical Threshold—When to Add Prandial Insulin

• When basal insulin approaches 0.5–1.0 units/kg/day (57–114 units) without achieving glycemic targets, add prandial insulin rather than further basal escalation 2
• Total daily insulin dose may exceed 1 unit/kg/day in severely obese adolescents with type 2 diabetes 2, 1
• Signs of overbasalization:
  • Basal dose > 0.5 units/kg/day without target achievement
  • Bedtime-to-morning glucose differential ≥ 50 mg/dL
  • Hypoglycemia episodes despite overall hyperglycemia
  • High glucose variability 2

Prandial Insulin Initiation (If Needed)

• Start with 4 units rapid-acting insulin before the largest meal or 10% of current basal dose 2
• Administer 0–15 minutes before meals 2
• Titrate by 1–2 units every 3 days based on 2-hour post-prandial glucose 2
• Target post-prandial glucose < 180 mg/dL 2

Insulin Taper After Ketosis Resolution

• After ketosis resolves (typically 2–6 weeks), taper basal insulin by 10–30% every few days if glycemic targets are met on home blood glucose monitoring 2, 1
• Continue metformin throughout the taper—it remains the foundation of therapy 2, 1

Additional Pharmacologic Options

If Metformin + Insulin Insufficient After 3–6 Months

• Add GLP-1 receptor agonist (liraglutide or semaglutide) for patients ≥ 10 years without personal/family history of medullary thyroid carcinoma or MEN 2 2, 1
• Consider empagliflozin (approved ages 10–17), which achieved HbA1c reduction of ≈ 0.84% in pediatric trials 1
• Both provide additional glycemic control and promote weight loss—critical in severe obesity 1

Monitoring Requirements

• Daily fasting glucose during titration to guide basal adjustments 2, 1
• Pre-meal glucose before each meal if prandial insulin is added 2
• 2-hour post-prandial glucose after meals to assess prandial adequacy 2
• HbA1c every 3 months until stable control achieved 2
• Reassess insulin dose every 2–3 days during active titration 1

Lifestyle and Multidisciplinary Care

• Implement family-centered nutrition program targeting 7–10% reduction in excess weight through reduced processed foods and increased fruits/vegetables 1
• Prescribe ≥ 60 minutes daily of moderate-to-vigorous physical activity including aerobic, muscle-strengthening, and bone-strengthening components 1
• Assemble multidisciplinary team: physician, diabetes educator, registered dietitian, behavioral health specialist 2, 1
• Screen for comorbidities: hypertension, dyslipidemia, microvascular complications 1

Critical Pitfalls to Avoid

• Do not postpone insulin when ketonuria is present, even if HbA1c < 8.5% 1
• Do not infer diabetes type solely from obesity—up to 6% of youth with type 2 diabetes present with DKA and may have positive autoantibodies 1
• Do not delay metformin until after ketosis resolves—start concurrently with insulin 1
• Do not continue escalating basal insulin beyond 0.5–1.0 units/kg/day without addressing post-prandial hyperglycemia 2
• Never discontinue metformin if autoantibodies become positive—transition fully to insulin-based regimen for type 1 diabetes 1

Advanced Therapeutic Consideration

• Metabolic surgery may be considered for adolescents with BMI > 35 kg/m², elevated HbA1c, and persistent serious comorbidities despite optimized lifestyle and pharmacologic therapy, performed by experienced surgeon within multidisciplinary framework 2, 1