Insulin secretion and insulin sensitivity in relation to glucose tolerance- Lessons from the Botnia Study

Recently, a new stage in glucose tolerance, impaired fasting glucose (IFG) (fasting plasma glucose level of 6.1-6.9 mmol/l), was introduced in additio n to impaired glucose tolerance (IGT) (2-h glucose level of 7.8-11.0 mmol/l ). It is not clear whether IFG and IGT differ with respect to insulin secre tion or sensitivity. To address this question, we estimated insulin secreti on (by measuring both insulin levels and the ratio of insulin-to-glucose le vels in 30-min intervals) and insulin sensitivity (by using the homeostasis model assessment [HOMA] index) from an oral glucose tolerance test (OGTT) in 5,396 individuals from the Botnia Study who had varying degrees of gluco se tolerance. There was poor concordance between IFG and IGT: only 36% (303 of 840) of the subjects with IFG had IGT, whereas 62% (493 of 796) of the subjects with IGT did not have IFG. Compared with subjects with normal gluc ose tolerance (NGT), subjects with IFG were more insulin resistant (HOMA-in sulin resistance [IR] values 2.64 +/- 0.08 vs. 1.73 +/- 0.03, P < 0.0005), had greater insulin responses during an OGTT (P = 0.0001), had higher waist -to-hip ratios (P < 0.005), had higher triglyceride and total cholesterol c oncentrations (P < 0.0005), and had lower HDL cholesterol concentrations (P = 0.0001). Compared with subjects with IFG, subjects with IGT had a lower incremental 30-min insulin-to-glucose area during an OGTT (13.8 +/- 1.7 vs. 21.7 +/- 1.7, P = 0.0008). Compared with subjects with IGT, subjects with mild diabetes (fasting plasma glucose levels <7.8 mmol/l) showed markedly i mpaired insulin secretion that could no longer compensate for IR and elevat ed glucose levels. A progressive decline in insulin sensitivity was observe d when moving from NGT to IGT and to subjects with diabetes (P < 0.05 for t rend), whereas insulin secretion followed an inverted U-shaped form. We con clude that IFG is characterized by basal IR and other features of the metab olic syndrome, whereas subjects with IGT have impaired insulin secretion in relation to glucose concentrations. An absolute decompensation of beta-cel l function characterizes the transition from IGT to mild diabetes.