Wei Jintao, Lu Shi-Yuan, Zhang Tianyue
Department of Emergency Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Province Clinical Research Center for Emergency and Critical Care Medicine, Hangzhou, China.
Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Front Endocrinol (Lausanne). 2025 Sep 12;16:1656453. doi: 10.3389/fendo.2025.1656453. eCollection 2025.
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.
我们报告了一名52岁的自身抗体阴性1型糖尿病（T1D）男性患者，该患者存在严重胰岛素抵抗（IR）。全外显子组测序（WES）在胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）基因中发现了一个杂合突变（c.248A>G，p.Lys83Thr；rs4402960），该突变与2型糖尿病（T2D）风险相关。尽管进行了强化胰岛素治疗，但该患者的胰岛素需求量仍显著升高（>1.5 U/kg/天；总计140 U/天），同时伴有持续性高血糖。估计的葡萄糖处置率（eGDR）为4.32 mg/kg/分钟，表明存在显著的IR。通过持续葡萄糖监测（CGM）排除了索马吉效应，该患者被认为存在IR。加用二甲双胍、阿卡波糖和达格列净降低了胰岛素需求量，并显著改善了血糖控制。该病例表明，与T2D相关的基因变异可能导致T1D中的IR，并强调了基因检测在指导靶向口服联合治疗中的潜在价值。
