Glycosylated Hemoglobin: Finally Ready for Prime Time as a Cardiovascular Risk Factor

More than 17 million people in the United States currently have diabetes, and this number is rapidly increasing (1). Affected individuals are at high risk for premature death as well as eye, kidney, nerve, cardiovascular, and other chronic diseases. Thus, the annual estimated costs of diabetes exceeded $130 billion in 2002 (2)—an increase of greater than 30% since 1998 (3). This societal burden, and evidence that the diabetes epidemic is being fueled by our current lifestyle (4, 5), means that diabetes is now an urgent public health problem.

But diabetes is just the measured tip of a much larger “dysglycemic iceberg.” Diabetes is diagnosed when the fasting plasma glucose level is consistently 7 mmol/L or greater (≥ 126 mg/dL) or when the 2-hour plasma glucose level (after drinking a 75-g glucose load) is consistently 11.1 mmol/L or greater (≥ 200 mg/dL). These thresholds are much higher than the “normal” fasting and 2-hour mean glucose levels of 5.1 mmol/L (92 mg/dL) and 5.4 mmol/L (97 mg/dL), respectively (6). These levels were chosen because they effectively differentiated individuals at high risk for eye disease from individuals at low risk (7). They were not chosen on the basis of risk for cardiovascular disease; as such, there is no a priori reason to believe that they would differentiate people at high versus low risk for cardiovascular disease. Indeed, it is now clear that fasting or 2-hour glucose levels that are well below the diabetes cutoffs are cardiovascular risk factors (8, 9) …