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

Abstract

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 24.3±2.9 years later in an unselected healthy non-obese population. Methods: The K-value of an IVGTT was determined in 267 healthy subjects (mean±SD: age 31.0±12.0 years, BMI 21.8±2.8 kg/m 2 ). First-phase insulin response to a glucose infusion test was estimated as an incremental 5-or 10-min (ΔI5 or ΔI10) value, and as insulinogenic indices (ΔI5/ΔG5 or ΔI10/ΔG10) adjusted for insulin sensitivity determined by homeostasis model assessment for insulin resistance ([ΔI5/ΔG5]/HOMA-IR). Results: At followup, 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 ΔI5/ΔG5, (ΔI5/ΔG5)/HOMA-IR and K-value. In multiple linear regression analysis, (ΔI5/ΔG5)/HOMA-IR, ΔI10, 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.

Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes

“…The b-cell-related indices were significantly decreased in diabetes converters, while insulin resistance-related parameters did not differ between converters and nonconverters. Several studies have shown that b-cell dysfunction is the major driving factor for the development of overt diabetes in Asians, Pima Indians, and Caucasians [27][28][29][30][31][32]. Differences in underlying b-cell function in each prediabetes category might contribute to the heterogeneous rate of progression to diabetes.…”

Risk factors for incident type 2 diabetes in individuals with a BMI of <27 kg/m2: the role of γ-glutamyltransferase. Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

“…In this regard, we found that plasma GGT was significantly correlated with the HOMA beta index [26] in our cohort (data not shown). Impaired early and total insulin secretion are viewed as strong determinants of future glucose tolerance in non-obese individuals and as the predominant features of newly diagnosed type 2 diabetes [27,28].…”

Effect of aging on islet beta-cell function and its mechanisms in Wistar rats

“…Glucose tolerance progressively declines with age, and the incidence of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) is increased in the elderly (DeFronzo 2004;Alvarsson et al 2005;Tfayli and Arslanian 2009). As a result of economic development and improvements in life expectancy, the prevalence of diabetes is rapidly growing in China (Yang et al 2010).…”