A 13-year-old lean girl has fasting plasma glucose of 132 mg/dL and HbA1c of 7.0 percent. She is asymptomatic, has no ketosis, and has acanthosis-free skin. Her father and paternal grandmother were diagnosed with diabetes before age 25 and are not overweight. C-peptide is preserved and anti-GAD65 and anti-islet cell antibodies are negative. What is the most appropriate next diagnostic step?

• A Start lifelong intensive insulin therapy as for type 1 diabetes
• B Begin metformin and lifestyle modification and review in six months
• C Perform molecular genetic testing for monogenic diabetes, targeting HNF1A ✓
• D Repeat an oral glucose tolerance test annually before deciding

Explanation

Young-onset diabetes in three consecutive generations with preserved C-peptide and negative autoantibodies indicates autosomal dominant monogenic diabetes. HNF1A-MODY is the most common subtype and classically responds to low-dose sulfonylurea, sparing the patient decades of unnecessary insulin. Metformin alone is a reasonable default for presumed type 2 diabetes, but the lean phenotype and strong vertical pedigree argue strongly for genetic confirmation first, since treatment differs fundamentally.

Reference: ISPAD Clinical Practice Consensus Guidelines, 2022 ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.