What is a normal glucose value?: Differences in indexes of plasma glucose homeostatis in subjects with normal fasting glucose

OBJECTIVE - To evaluate differences in indexes of plasma glucose/insulin homeostasis and cardiovascular disease risk factors among subjects with normal fasting glucose (NFG), impaired fasting glucose, or glucose intolerance. Although individuals with fasting plasma glucose (FPG) concentrations >5.4 mmol/l but <6.1 mmol/l have been shown to have an increased risk of developing type 2 diabetes over 5 years, little is known about glucose metabolism abnormalities in this population. RESEARCH DESIGN AND METHODS - We compared insulin secretion and insulin sensitivity using several indexes derived from an oral glucose tolerance test (OGTT) in 668 subjects from the Quebec Family Study who had varying degrees of FPG. RESULTS - There was a progressive decline in indexes of beta-cell function and insulin sensitivity when moving from NFG to type 2 diabetes. Compared with subjects with low NFG (FPG <4.9 mmol/l), subjects with high NFG (FPG 5.3-6.1 mmol/l) were more insulin resistant (P < 0.01), had higher insulin and C-peptide responses during an OGTT (P < 0.05), and had reduced insulin secretion (corrected for insulin resistance). Subjects with high NFG were also characterized by higher plasma triglyceride levels and reduced HDL cholesterol concentrations and by a smaller LDL particle size. All these differences remained significant, even after adjustment for age, sex, BMI, and waist circumference. In addition, subjects with mid NFG (FPG 4.9-5.3 mmol/l) were characterized by impaired insulin secretion, decreased insulin sensitivity, higher triglyceride concentrations, and lower HDL cholesterol concentrations compared with subjects with low NFG. CONCLUSIONS - independent of age, sex, and adiposity, there are differences in indexes of plasma glucose/insulin homeostasis and in cardiovascular risk factors among subjects with low, mid, and high NFG, suggesting the presence, in the upper normal glucose range, of abnormalities in glucose homeostasis, which may predispose to type 2 diabetes.