Abstract
Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥8.6 mmol/l (155 mg/dl) at 1 h during an oral glucose tolerance test (OGTT) can identify individuals at high risk for type 2 diabetes among those who have normal glucose tolerance (NGT 1 h-high). The aim of this study was to examine whether NGT 1 h-high have a decrease in insulin clearance, as compared with NGT individuals with 1-h post-load glucose <8.6 mmol/l (l (155 mg/dl, NGT 1 h-low). To this end, 438 non-diabetic White individuals were subjected to OGTT and euglycemic-hyperinsulinemic clamp to evaluate insulin clearance and insulin sensitivity. As compared with NGT 1 h-low individuals, NGT 1 h-high had significantly higher 1-h and 2-h post-load plasma glucose and 2-h insulin levels as well as higher fasting glucose and insulin levels. NGT 1 h-high exhibited also a significant decrease in both insulin sensitivity (P<0.0001) and insulin clearance (P = 0.006) after adjusting for age, gender, adiposity measures, and insulin sensitivity. The differences in insulin clearance remained significant after adjustment for fasting glucose (P = 0.02) in addition to gender, age, and BMI. In univariate analyses adjusted for gender and age, insulin clearance was inversely correlated with body weight, body mass index, waist, fat mass, 1-h and 2-h post-load glucose levels, fasting, 1-h and 2-h post-load insulin levels, and insulin-stimulated glucose disposal. In conclusion, our data show that NGT 1 h-high have a reduction in insulin clearance as compared with NGT 1 h-low individuals; this suggests that impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia.
Highlights
Type 2 diabetes mellitus is a metabolic disorder of pandemic proportion, and primary prevention of the disease is an essential strategy to restrain the rapid increase in its prevalence and to control the economic burden on the health care system
Significant differences between the three groups were observed with respect to gender, and age (NGT 1 h-high and impaired glucose tolerance (IGT) individuals were older than normal glucose tolerance (NGT) 1 h-low individuals)
NGT 1 h-high exhibit a reduction in insulin clearance similar to the one observed in IGT individuals, who are considered at high risk for type 2 diabetes
Summary
Type 2 diabetes mellitus is a metabolic disorder of pandemic proportion, and primary prevention of the disease is an essential strategy to restrain the rapid increase in its prevalence and to control the economic burden on the health care system. It is well established that individuals with IGT are at increased risk for type 2 diabetes compared with individuals with normal glucose tolerance (NGT), but only 35–50% of individuals with IGT develop type 2 diabetes after 5–10 years [5,6]. Prospective studies have shown that ,30–40% of individuals who convert to type 2 diabetes have NGT at baseline [5], indicating that the sole use of IGT to identify individuals at increased risk for type 2 diabetes may overlook a large group of individuals that will develop the disease. NGT 1 h-high individuals are characterized by a cluster of metabolic and cardiovascular abnormalities including insulin resistance and reduced b-cell function [9], elevated inflammation markers [10], increased levels of liver enzymes [11], lower plasma insulin-like growth factor 1 concentrations [12], and elevated uric acid levels [13]. NGT 1 h-high individuals show signs of subclinical organ damage including common carotid artery thickness [14], vascular stiffness [15], diminished estimated glomerular filtration rate [16], left ventricular hypertrophy [17], and left ventricular diastolic dysfunction [18], all independent predictors of subsequent cardiovascular events
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