Dissociation Of Glucose Homeostasis From Insulin Sensitivity In College-age Subjects At Risk For Type 2 Diabetes

Abstract

It has been estimated that insulin resistance (IR) affects ∼24% of US adults overall. Glucose intolerance due to both ⊔-cell destruction and peripheral insulin resistance are characteristic of a pre-clinical phase before the advent of frank Type 2 diabetes. IR is often accompanied by hyperinsulinemia and may predispose to atherosclerosis. Thus, pre-disease intervention may be most appropriate at a stage of IR but before glucose intolerance. PURPOSE To examine variation in insulin sensitivity in a healthy cohort of college-age students with a family history of Type 2 diabetes. METHODS Six young (19–26 y) subjects with a family history of Type 2 diabetes performed a standard OGTT [1 g/kg body weight (up to 75 g)]. Venous blood samples were taken at 0, 30, 45, 60, 75, 90 and 120 min. for measurements of plasma glucose (YSI 2300 glucose oxidase analyzer) and insulin immunoassay (Mercodia Insulin ELISA). Hepatic insulin sensitivity index (ISI) was calculated by the HOMA (ISIHOMA) while incremental areas under the curve (AUCs-baseline) were calculated with the trapezoid method to determine mean OGTT glucose and mean OGTT insulin and used to estimate whole-body insulin sensitivity by the index of Matsuda and De Fronzo (ISICOMPOSITE). Demographic, anthropometric and medical information (gender, BMI, ethnicity, proliferation of Type 2 diabetes in the family history, fasting plasma glucose and other medical considerations correlated with impaired glucose tolerance), predictive for high risk for diabetes, were used to calculate a composite numerical risk score. RESULTS All subjects had normal glucose tolerance based on American Diabetic Association (ADA) criteria for fasting plasma glucose (mean mg/dl + SD; 80.89±4.86) and 2-h OGTT (89.28±15.71). Mean OGTT glucose showed similar normalcy (102.08±12.17) but was accomplished by a large intersubject range of fasting plasma insulin (mean uM/L + SD; 4.86±1.97) or mean OGTT insulin (30.76 + 16.79). This was reflected in the large intersubject range of ISICOMPOSITE, (15.91±6.26) which was highly correlated with the measure of fasting insulin sensitivity, ISIHOMA, (r2 = 0.81). Individual risk factors and composite risk scores also showed intersubject variability, but were not correlated with either ISICOMPOSITE or ISIHOMA. CONCLUSIONS In these 6 college-age subjects, normal glucose homeostasis was observed despite a range of risk factors that predispose them to Type 2 diabetes. Exaggerated insulin responses in both fasting and during OGTT portend that characterizing insulin sensitivity only by measures of glucose homeostasis can lead to missed markers of insulin resistance indicative of pre-clinical Type 2 diabetes.