In vivo endothelial dysfunction characterizes patients with impaired fasting glucose.

Abstract

OBJECTIVE: The American Diabetes Association has recently defined a new category of abnormal glucose homeostasis called "impaired fasting glucose" (IFG), where glucose levels do not meet the criteria of diabetes but are too high to be considered normal. We determined whether endothelial dysfunction is a characteristic of subjects with IFG. RESEARCH DESIGN AND METHODS: In vivo vasodilatory responses to intra-arterial infusions of endothelium-dependent (acetylcholine [ACh]) and -independent (sodium nitroprusside [SNP]) vasoactive agents were determined in 17 IFG subjects (age 63 +/- 1 years, BMI 26.5 +/- 0.8 kg/m2, serum LDL cholesterol 3.5 +/- 0.2 mmol/l) with fasting plasma glucose levels of 117 +/- 1 mg/dl and in 12 subjects with normal fasting plasma glucose concentrations. RESULTS: The blood-flow response to the low dose of ACh was 46% (5.9 +/- 0.7 vs. 10.9 +/- 1.3 ml.dl-1.min-1, IFG vs. normal, P < 0.01) and to the high dose was 31% (9.1 +/- 1.2 vs. 13.2 +/- 1.5 ml.dl-1.min-1, P < 0.05, respectively) lower in the IFG than in the normal subjects. In contrast, blood-flow responses to both low (7.8 +/- 0.5 vs. 9.0 +/- 0.9 ml.dl-1.min-1, IFG vs. normal, NS) and high (11.6 +/- 1.2 vs. 12.3 +/- 1.3 ml.dl-1.min-1, NS, respectively) doses of SNP were comparable. The ratio of endothelium-dependent to -independent blood flow was 40% lower in the IFG (0.75 +/- 0.1) than in the normal (1.24 +/- 0.1, P < 0.001) subjects. Both fasting plasma glucose (r = -0.48, P < 0.01) and glycosylated hemoglobin (r = -0.42, P < 0.05) were inversely correlated with endothelium-dependent vasodilation but not with other parameters, such as weight, blood pressure, or lipids. CONCLUSIONS: We conclude that vascular dysfunction is associated with abnormal, although nondiabetic, glucose homeostasis.