A 17-year-old lean girl has fasting glucose 138 mg/dL. Her mother and maternal grandfather were diagnosed with diabetes before age 25 and are not obese. She has no ketosis, negative autoantibodies, and C-peptide is preserved. Which feature best supports sulfonylurea monotherapy over insulin as initial treatment?

• A Presence of obesity and acanthosis nigricans
• B Elevated triglycerides with low HDL cholesterol
• C Positive GAD65 antibodies indicating slow autoimmune destruction
• D A heterozygous HNF1A mutation, since HNF1A-MODY is exquisitely sulfonylurea responsive ✓

Explanation

MODY due to HNF1A mutation presents as early-onset, autosomal dominant, non-ketotic diabetes in lean individuals with preserved C-peptide, and these patients are remarkably sensitive to sulfonylureas, often achieving better control than with insulin. Positive GAD antibodies would point toward autoimmune type 1 diabetes requiring insulin, so option C argues against the key.

Reference: Williams Textbook of Endocrinology, 14th ed.

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