Metabolic heterogeneity in impaired glucose tolerance☆

Abstract 

Type II (non—insulin-dependent) diabetes mellitus is a metabolically heterogeneous condition, and is invariably preceded by impaired glucose tolerance (IGT). We examined whether, metabolic heterogeneity is a feature of IGT. Three subject groups were studied: IGT subjects with two or more living non—insulin-dependent diabetic relatives (IGT_WF, n = 17), and IGT subjects (IGT_WOF, n = 17) and subjects with normal glucose tolerance (NGT, n = 25) without a family history of diabetes. Glucose tolerance, glucose (K_ITTG) and nonesterified fatty acid (K_ITNEF) insulin sensitivity, and first-phase insulin secretion (FPIS) were assessed by oral glucose tolerance (OGTT), insulin tolerance (ITT), and intravenous glucose tolerance (IVGTT) tests, respectively. Comparison of groups was made by ANOVA and t test. The three groups were matched for age, gender, body mass index (BMI), and waist to hip ratio (WHR). IGT_WOF and IGT_WF subjects had comparable 2-hour plasma glucose levels on OGTT and insulin secretion and KITTG were decreased to comparable degrees. However, in comparison to IGT_WF subjects, IGT_WOF subjects had increased fasting serum triglyceride (geometric mean, 1.8 [range, 0.8 to 4.5] v 1.1 [0.4 to 2.5] mmol. L⁻¹, P = .02) and 2-hour plasma nonesterified fatty acid ([NEFA] mean ± SD, 0.12 ± 0.07 v 0.08 ± 0.03 mmol · L₋₁, P < .02) levels and decreased K^ITTFNEF values (4.0 [1.7 to 8.9] v 6.2 [2.8 to 12.1] · min⁻¹, P < .02). Thus, the two IGT groups had comparable changes in glucose metabolism, but IGT_WOF subjects had additional abnormalities of lipid metabolism. In conclusion, metabolic heterogeneity is a feature of IGT, and this may reflect underlying etiological heterogeneity.

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