Role of glycemia in cardiovascular disease

Jacqueline Dekker (Amsterdam, the Netherlands) discussed the association between hyperglycemia and cardiovascular disease (CVD), particularly addressing A1C measurement in nondiabetic individuals. A1C, she noted, is considered a gold-standard measure of chronic glycemia in diabetic patients. In nondiabetic populations, its implications are somewhat less clear. In a study of 648 apparently healthy individuals, 12% had an elevated total A ₁ level (measured in that study) not explained by measurement error or glucose intolerance and remaining in the same range over 3.5 years in 90% of those initially with high and in 68% of those initially with low baseline levels (1). There was no correlation with glucose tolerance, with caloric intake, or with physical activity, but A ₁ level was associated with cigarette use and with clinically overt atherosclerosis, leading Dekker to conclude that “factors unrelated to glucose metabolism are the main determinants of A ₁” in nondiabetic individuals, perhaps with bearing on risk of what are considered complications of diabetes. A subsequent study of 3,240 nondiabetic individuals showed weak correlation of A1C with fasting and 2-h glucose, cholesterol, and insulin. Weak but significant correlations were also found with erythrocyte characteristics, and cigarette use was associated with higher A1C, again suggesting nonglycemic effects on hemoglobin glycation (2). In the Islington Diabetes Survey, 1,084 participants had glucose tolerance tests and four different A1C assays. The 2-h postload glucose explained 19–41% of the variation in A1C, depending on the assay, and 26–48% of the variation was explained by the fasting glucose, with low and high glycators remaining constant over 4 years (3). If 50–80% is not explained by glycemia, the implication is, again, that although …