No evidence for genetically determined alteration in insulin secretion or sensitivity predisposing to type 1 diabetes: A study of identical twins

OBJECTIVE - To determine whether inherited changes in insulin secretion or sensitivity could predispose to type 1 diabetes, we studied identical twins of type 1 diabetic patients. RESEARCH DESIGN AND METHODS - We studied prospectively a consecutive series of 27 identical twins of patients with type 1 diabetes who were initially nondiabetic, as well as 14 control subjects, over a period of 18 years. Of these 27 twins, 15 remain nondiabetic (now estimated at low disease risk) and 12 developed diabetes (pre-diabetic twins). Subjects were tested when not diabetic on at least two occasions with an intravenous glucose tolerance test (IVGTT), and we estimated insulin secretion as first-phase insulin response (FPIR), glucose clearance (K_g), and insulin sensitivity both by homeostasis model assessment of insulin resistance (HOMA-IR) and relative to insulin response by the basal HOMA-IR-to-FPIR ratio. RESULTS - Twins now at low risk and control subjects had similar fasting blood glucose and insulin levels, FPIR, K_g, HOMA-IR, and HOMA-IR-to-FPIR ratio. In contrast, pre-diabetic twins compared with control twins had higher fasting insulin levels (10.3 ± 6.0 vs. 4.6 ± 4.0 mIU/ml), lower FPIR (245 ± 129 vs. 796 ± 622 mIU · ml^-1 · 10 min^-1), lower K_g (1.5 ± 0.6 vs. 2.6 ± 0.8% per min), and higher HOMA-IR-to-FPIR ratio (0.007 ± 0.005 vs. 0.001 ± 0.0009) (all P <0.01). CONCLUSIONS - These observations in low-risk nondiabetic identical twins failed to identify a familial alteration in either insulin secretion or sensitivity predisposing to type 1 diabetes.