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Point: Postprandial Glucose Levels Are a Clinically Important Treatment Target

American Diabetes Association
Publication Date
DOI: 10.2337/dc10-0634
  • Point/Counterpoint
  • Biology
  • Medicine


Point: Postprandial Glucose Levels Are a Clinically Important Treatment Target The results of the Nateglinide AndValsartan in Impaired GlucoseTolerance Outcomes Research (NAVIGATOR) trial have been recently reported (1–2). Nateglinide, a member of the meglitinide class, which has been shown to lower postprandial hyperglyce- mia 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 cardio- vascular events but significantly—even marginally—reduced the onset of new di- abetes (2). The negative results of nateg- linide immediately raised the concern about the possibility that postprandial hy- perglycemia could be considered an inde- pendent risk factor for cardiovascular disease (CVD) and whether its treatment may give any advantage in the manage- ment 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 �-cell glucose sensitivity and whole-body insulin sensitivity are strong predictors of a progression to hyperglyce- mia (4). Conversely, numerous studies have shown that acute insulin secretion defects represent a powerful early predic- tor of diabetes progression. During the progression from normal glucose tolerance to increasingly severe type 2 diabetes, first-phase insulin secre- tion (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 in- dividuals. In another analysis, a marked and increasing loss of the early-phase �-cell secretory response to a meal chal- lenge correl

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