Postprandial Glucose Regulation and Diabetic Complications

Ceriello A, Hanefeld M, Leiter L, Monnier L, Moses A, Owens D, Tajima N, Tuomilehto J. Arch Intern Med. 2004;164:2090-2095.

Cardiovascular disease is responsible for much of the increased morbidity and mortality related to type 2 diabetes. There is emerging evidence linking postprandial hyperglycemia to diabetes complications due to the harmful effects of postprandial hyperglycemia on the vasculature. Although still under debate, it has been suggested that controlling postprandial glucose levels may be a viable strategy for preventing cardiovascular complications in people with diabetes.

There is no generally accepted method for measuring postprandial glucose levels; operational definition of this factor varies from study to study. Numerous studies have established the relationship between postprandial glucose levels and cardiovascular complications, concluding that 2-hour postchallenge glucose levels were a better predictor of cardiovascular events than A1C levels. Specifically, the DECODE (Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe) study confirmed that 2-hour postchallenge hyperglycemia after an oral glucose tolerance test (OGTT) is correlated with increased mortality, and is a more accurate predictor of mortality than the fasting plasma glucose level.

The pathophysiology of cardiovascular risk is complex. Although most cardiovascular risk factors are influenced by glycemic increases, dyslipidemia is also an important risk factor for cardiovascular disease, and postprandial dyslipidemia contributes to this risk. It has been observed that atherogenic dyslipidemia is amplified in the postprandial state, leading some to question the contribution of postprandial hyperglycemia to cardiovascular risk. However, evidence suggests that postprandial hypertriglyceridemia and hyperglycemia are independently associated with endothelial dysfunction (via oxidative stress), confirming the atherogenic properties of postprandial hyperglycemia independent of the effects of dyslipidemia.

Overall glycemic control is measured by A1C levels; A1C is the primary therapeutic target, in spite of the fact that it does not take blood glucose excursions into account and may not be the most clinically useful assessment of cardiovascular risk in diabetes. It has been shown that postprandial hyperglycemia is the largest contributor of daytime hyperglycemia, contributing up to 70%. Further, the influence of postprandial hyperglycemia is greater at tighter levels of glycemic control.

The impact of postprandial glycemic excursions on overall glycemic control can be reduced through specific pharmacologic agents. Acarbose, sulfonylureas, repaglinide, thiazolidinediones, and metformin all either directly or indirectly impact postprandial glycemia. However, the effectiveness of these agents lessens as β-cell mass and function decline, suggesting that the clinical expressions of hyperglycemia are primarily caused by insulin deficiency as type 2 diabetes advances. When this occurs, very-rapid-acting insulin analogues administered either as monotherapy or basal-bolus therapy are useful to reduce meal-related glycemic excursions.

It is a well-known fact that the control of hyperglycemia plays a critical part in diabetes management. Recent studies indicate that controlling postprandial glucose levels can help to maximize metabolic control. The deleterious effects of poor glucose maintenance on the vasculature of diabetic patients warrants a closer look at postprandial glucose as an indicator for cardiovascular events.