Postprandial hyperglycemia and endothelial function in type 2 diabetes: focus on mitiglinide

Abstract

The risk of cardiovascular complication in a diabetes patient is similar to that in a nondiabetic patient with a history of myocardial infarction. Although intensive control of glycemia achieved by conventional antidiabetic agents decreases microvascular complications such as retinopathy and nephropathy, no marked effect has been reported on macrovascular complications or all-cause mortality. Evidence from VADT, ACCORD, and ADVANCE would suggest that glycemic control has little effect on macrovascular outcomes. Moreover, in the case of ACCORD, intensive glycemic control may be associated with an increased risk of mortality. There is sufficient evidence that suggests that postprandial hyperglycemia may be an independent risk factor for cardiovascular disease in diabetes patients. However, there are no prospective clinical trials supporting the recommendation that lowering postprandial blood glucose leads to lower risk of cardiovascular outcomes. Mitiglinide is a short-acting insulinotropic agent used in type 2 diabetes treatment. It has a rapid stimulatory effect on insulin secretion and reduces postprandial plasma glucose level in patients with type 2 diabetes. Because of its short action time, it is unlikely to exert adverse effects related to hypoglycemia early in the morning and between meals. Mitiglinide reduces excess oxidative stress and inflammation, plays a cardioprotective role, and improves postprandial metabolic disorders. Moreover, mitiglinide add-on therapy with pioglitazone favorably affects the vascular endothelial function in type 2 diabetes patients. These data suggest that mitiglinide plays a potentially beneficial role in the improvement of postprandial hyperglycemia in type 2 diabetes patients and can be used to prevent cardiovascular diseases. Although the results of long-term, randomized, placebo-controlled trials for determining the cardiovascular effects of mitiglinide on clinical outcomes are awaited, this review is aimed at summarizing substantial insights into this topic.

Figure 1

Effect of mitiglinide add-on therapy on endothelial function. Reactive hyperemia-peripheral arterial tonometry (RH-PAT) index was measured for evaluating vascular endothelial function in type 2 diabetes patients before and after the 12-week mitiglinide add-on therapy.

Figure 2

The effects of mitiglinide on endothelial function and preventing cardiovascular disease. Multiple risk factors induce vascular endothelial dysfunction and the subsequent atherosclerosis progression. FFA, free fatty acids; oxLDL, oxidized low-density lipoprotein.