Substantial inter-individual variations in insulin secretion and sensitivity across the glucometabolic spectrum

Impaired insulin secretion and action are important for development of type 2 diabetes (T2D) and metabolic syndrome (MetS). Despite recognized heterogeneity of these glucometabolic disorders, few data are available of biological variation in insulin secretion and action among individuals with T2D and MetS. The aim of this study was to explore the inter-individual variations using gold standard methods in a cross-sectional study of two independent cohorts of phenotypically well-characterized subjects. Cohort I included 486 subjects with MetS, and cohort II 62 subjects with established T2D. First phase insulin secretion was defined as the incremental area under the curve 0-8 min (iAUC_0-8 min) during an intravenous glucose tolerance test (IVGTT). Insulin sensitivity was measured as the insulin sensitivity index (S_I) modelled from IVGTT in cohort I, and in II as total glucose disposal (TGD) estimated from a euglycaemic-hyperinsulinaemic clamp. Variation is given as total range and, fold-variation between 5%- and 95%-percentile. The iAUC_0-8 min ranged from -60 to 3397 mUL^-1min^-1 among subjects with MetS and from -263 to 1194 mUL^-1min^-1 in subjects with T2D, representing a more than 10-fold variation. Insulin sensitivity ranged from S_I 0.19 to 15.29 (mU/L)^-1min^-1 among subjects with MetS and TGD 12.9-101.6 μmolkgFFM^-1min^-1 in subjects with T2D, representing a 6.8 and 5.5-fold variation, respectively. The other components of MetS; BMI, waist-hip ratio, HDL-cholesterol, triglycerides and blood pressure (BP), showed a 1.4-4.7-fold variation. In conclusion, our data demonstrated extensive inter-individual variations in insulin secretion and sensitivity. These variations may be essential to take into account when planning clinical research and treatment in subjects with T2D and MetS.