Inflammation and insulin resistance.

Abstract

This Is the second of two articles describing a symposium on the relationship between inflammation and insulin resistance that was held in Niagra Falls, NY, 20–21 September 2002. Antonio Ceriello (Udine, Italy) discussed the role of glucose intake and postprandial hyperglycemia in the development of diabetes complications, as well as the relationship of hyperglycemia to oxidative stress. The DECODE (Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe) study showed high 2-h postload glucose to be associated with increased mortality independent of fasting glucose (1), and the Pacific and Indian Ocean Study showed isolated 2-h hyperglycemia to double the risk of mortality (2). The Funagata Diabetes Study showed that impaired glucose tolerance (IGT) but not impaired fasting glucose was a risk factor for cardiovascular disease (CVD) (3). There is evidence that lowering postprandial glucose improves outcome. Post hoc analysis of the STOP-type 2 diabetes study showed that myocardial infarction and hypertension decrease with use of the prandial glucose-lowering agent acarbose (4). In the Kumamoto study, postprandial hyperglycemia strongly predicted retinopathy and nephropathy (5). Endothelial dysfunction (ED) is a potential mediator of the effect of prandial glycemia, with altered vasodilation and procoagulant abnormalities. ED can be induced by hyperglycemia following a 75-g oral glucose load in persons with normal or IGT or with diabetes, with reduction of flow-mediated brachial artery dilation proportional to the degree of hyperglycemia (6). In a study of 225 persons with hypertension followed for 32 months, forearm ED was a marker of future CVD events (7), with a 4.5-year follow-up of 281 persons showing both ED and measures of oxidative stress to predict CVD events (8). Acute hyperglycemia may suppress vasodilation, which may involve oxidant stress, as it is reversed with antioxidant or l-arginine treatment (9). Glucose increases endothelial cell free radical production leading …