K-value and low insulin secretion in a non-obese white population:: predicted glucose tolerance after 25 years

Aims/hypothesis: Insulin resistance and insulin deficiency are proposed as risk factors for IGT and type 2 diabetes. We assessed the predictive value of initial parameters for the outcome of an OGTT performed 24.32.9 years later in an unselected healthy non-obese population. Methods: The K-value of an IVGTT was determined in 267 healthy subjects (meanSD: age 31.012.0 years, BMI 21.82.8 kg/m2). First-phase insulin response to a glucose infusion test was estimated as an incremental 5- or 10-min (DI5 or DI10) value, and as insulinogenic indices (DI5/DG5 or DI10/DG10) adjusted for insulin sensitivity determined by homeostasis model assessment for insulin resistance ([DI5/DG5]/HOMA-IR). Results: At follow-up, six subjects had type 2 diabetes and 47 had IGT; 214 retained normal glucose tolerance. Insulin sensitivity and early (30 min) insulin response decreased with decreasing outcome OGTT. Blood glucose (2 h) at OGTT correlated positively with initial age and BMI, and negatively with DI5/DG5, (DI5/DG5)/HOMA-IR and K-value. In multiple linear regression analysis, (DI5/DG5)/HOMA-IR, DI10, K-value, age, HOMA estimate of insulin secretion, and fasting plasma glucose were significantly associated with 2-h OGTT blood glucose. Similar results were obtained on comparing differences between subjects with normal and decreased (IGT+diabetes) glucose tolerance. Conclusions/interpretation: In 267 non-obese healthy subjects, initial K-value and first-phase insulin response to glucose adjusted for insulin sensitivity, but not insulin sensitivity itself, were strong predictors of the outcome of an OGTT performed 25 years later. Thus, in contrast to obese or other high-risk populations, in lean subjects, decreased beta cell function, but not insulin resistance itself, determines future glucose tolerance.