Point: Postprandial Glucose Levels Are a Clinically Important Treatment Target

The results of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial have been recently reported (1–2). Nateglinide, a member of the meglitinide class, which has been shown to lower postprandial hyperglycemia by increasing the first phase of insulin secretion, was not effective in decreasing both the new cases of diabetes and the new cardiovascular events in a population at high risk (1). Valsartan, an angiotensin (AT-1) blocker, was ineffective on cardiovascular events but significantly—even marginally—reduced the onset of new diabetes (2). The negative results of nateglinide immediately raised the concern about the possibility that postprandial hyperglycemia could be considered an independent risk factor for cardiovascular disease (CVD) and whether its treatment may give any advantage in the management of diabetes (3). Diabetologists have long debated whether the lack of insulin action (insulin resistance) or impaired insulin secretion represents the primary pathological mechanism underlying type 2 diabetes. Recent analyses confirm that impaired pancreatic β-cell glucose sensitivity and whole-body insulin sensitivity are strong predictors of a progression to hyperglycemia (4). Conversely, numerous studies have shown that acute insulin secretion defects represent a powerful early predictor of diabetes progression. During the progression from normal glucose tolerance to increasingly severe type 2 diabetes, first-phase insulin secretion (FPIS) is an early casualty. Prior to the diagnosis of diabetes, insulin response to mealtime glucose becomes delayed and blunted; eventually, it is lost (5). In a landmark study, Polonsky et al. (5) showed that FPIS responses were more sluggish and less dramatic in diabetic individuals. In another analysis, a marked and increasing loss of the early-phase β-cell secretory response to a meal challenge correlated with increasing postprandial hyperglycemia in a group of individuals recently diagnosed with diabetes (6). Together these data indicate that declining FPIS and postprandial hyperglycemia are key …