Case Report: Insulin resistance in type 1 diabetes mellitus: the role of genetic factors

Abstract

We report a 52-year-old man with autoantibody-negative type 1 diabetes (T1D) who presented with severe insulin resistance (IR). Whole-exome sequencing (WES) identified a heterozygous mutation in the IGF2BP2 gene (c.248A>G, p. Lys83Thr; rs4402960), associated with type 2 diabetes (T2D) risk. Despite intensive insulin therapy, the patient exhibited markedly elevated insulin requirements (>1.5 U/kg/day; total, 140 U/day) alongside persistent hyperglycemia. The estimated glucose disposal rate (eGDR) was 4.32 mg/kg/min, indicating significant IR. The Somogyi phenomenon was ruled out via continuous glucose monitoring (CGM), and the patient was deemed to have IR. The addition of metformin, acarbose, and dapagliflozin reduced insulin requirements and significantly improved glycemic control. This case suggests that T2D-associated genetic variants may contribute to IR in T1D and underscores the potential value of genetic testing in guiding targeted oral combination therapy.