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

Abstract

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. 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. 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). 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.