Postprandial physiology and the pathogenesis of type 2 diabetes mellitus

Abstract

Background: Patients with type 2 diabetes mellitus (DM) have an increased risk of cardiovascular morbidity and mortality. Recent studies implicate postprandial hyperglycemia as an important driver of the increased risk of cardiovascular disease in patients with type 2 DM or prediabetes.

Objectives: This article reviews the postprandial physiology of glucose and insulin, the role of postprandial hyperglycemia in the increased risk of cardiovascular disease in patients with type 2 DM, and the role of insulin and other agents in reducing that risk.

Methods: Relevant articles for this review were identified through a search of MEDLINE (1999-2007; Englishlanguage articles only). The search terms used were glucose, insulin, pathophysiology, postprandial, hyperglycemia, and cardiovascular risk.

Results: The concentration of glucose in plasma is determined by the relative rates of glucose entering and leaving the circulation. The rate at which intestinally absorbed glucose disappears from the circulation is controlled primarily by insulin. Insulin stimulates cells in insulin-sensitive tissue to increase uptake of glucose and acts directly on the liver to suppress hepatic glucose production and postprandial pancreatic a-cell secretion of the glucoregulatory hormone glucagon. Elevations of glucose in plasma may increase cardiovascular risk in several ways. Postprandial hyperglycemia has been shown to increase the production of free radicals and attenuate antioxidant defenses, activate prothrombotic pathways, induce vasoconstriction, and increase circulating levels of adhesion molecules. Postprandial hyperglycemia also has been correlated with carotid intima-media thickness, a surrogate marker for cardiovascular dysfunction. Insulin may reduce cardiovascular risk. Insulin is a known vasodilator that increases blood flow through the macrovasculature and microvasculature. It also appears to have direct anti-inflammatory effects, suppressing the generation of reactive oxygen species and proinflammatory transcription factors, as well as antiatherogenic effects, reducing postprandial hypertriglyceridemia, total atherosclerotic area, and number of aortic lesions.

Conclusions: The adverse effects of postprandial hyperglycemia, together with the accompanying dyslipidemia, on cardiovascular health suggest that postprandial hyperglycemia should be a primary target of antidiabetic therapy. There is ample evidence to show that reducing postprandial hyperglycemia in patients with type 2 DM or prediabetes can reduce cardiovascular risk. Insulin may be an ideal agent for the treatment of postprandial hyperglycemia owing to its antihyperglycemic and cardioprotective effects.