Postprandial peaks as a risk factor for cardiovascular disease: epidemiological perspectives

A key issue in diabetes care is selecting glucose parameters to monitor and control. The recommendations of the American Diabetes Association for glycaemic control do not address postprandial glucose (PPG), but patients with type 2 diabetes experience wide variations in glucose levels after meals. We have observed a remarkable increase in plasma glucose two hours after breakfast and/or lunch in most non-insulin-treated patients; for up to 40% of them the increase is >40 mg/dl (2.2 mmol/l). As many as 70% of patients with an HbA1c <7% have PPG values >160 mg/dl (8.9 mmol/l) after meals. Fasting plasma glucose (FPG) is a poor indicator of plasma glucose at other times. The coefficient of correlation of FPG with plasma glucose at other times ranges from 0.50-0.70. Nor is the correlation of FPG with HbA1c very strong: in hundreds of determinations of HbA1c and FPG in our patients, the coefficient of correlation was not greater than 0.73. For the same FPG value, HbA1c varied markedly, and vice versa; further, the correlation between PPG and HbA1c was no higher than that between FPG and HbA1c (r = 0.65). Thus, monitoring in type 2 diabetes should include PPG along with FPG and HbA1c. Recent data provide direct and indirect evidence suggesting that PPG is independently related to cardiovascular disease (CVD), and supporting the idea that PPG should be assessed and glucose excursions with meals should be controlled: 1. Studies conducted by other investigators and ourselves in patients with type 2 diabetes have shown that the incidence of CVD is independently related to postprandial or post-OGTT (oral glucose tolerance test) blood glucose at baseline. In addition, data collected in the general population show an association between 2-hour OGTT plasma glucose (a surrogate of PPG) and cardiovascular morbidity and mortality that is independent of FPG. Also, subjects with impaired glucose tolerance (IGT) and isolated post-challenge hyperglycaemia have an increased cardiovascular risk over subjects with normal glucose tolerance (NGT). We found that IGT subjects had a risk of carotid stenosis 3-fold higher than subjects with NGT, even after adjustment for several confounders. Thus, a modest increase in post-OGTT plasma glucose and, by extrapolation, PPG seems to have a major detrimental effect on the arteries. 2. When FPG and/or HbA1c were the targets of glucose control in studies of patients with type 2 diabetes (the UGDP, VACSDM, and UKPDS) the effects on CVD were minimal. However, when the targets of glucose control included PPG (the Kumamoto Study and DIGAMI Study) favorable effects on CVD were observed. 3. There is experimental data suggesting that acute hyperglycaemia can exert deleterious effects on the arterial wall through mechanisms including oxidative stress, endothelial dysfunction, and activation of the coagulation cascade. This evidence prompted the European Diabetes Policy Group to set postprandial targets for blood glucose control: postprandial peaks should not exceed 135 mg/dl (7.5 mmol/ml) to reduce arterial risk and should not exceed 160 mg/dl (8.9 mmol/l) to reduce microvascular risk. Thus, glucose care in diabetes is not only "fasting glucose care" or "HbA1c care" but is also "postprandial glucose care."