ABSTRACT
For most of the 20th century, cardiovascular disease (CVD) was identified as the major cause of morbidity and mortality in the developed world. During this period, there was considerable effort to understand the underlying biology of the disease and to identify the contributing risk factors. As risk factors were identified, it became apparent that more than one major factor was often present in the same individual. Toward the end of the century, the clustering of cardiovascular risk factors was first described, most notably the simultaneous presence of obesity, Type 2 diabetes mellitus, hyperlipidemia, and hypertension (1-3). Although insulin resistance (i.e., impaired insulin-stimulated glucose uptake) as a feature of Type 2 diabetes mellitus had been first described many years earlier (4), hyperinsulinemia (5,6), hyperlipidemia (7-9), obesity (10-13), and hypertension (10,11,14) were also found to be key features of Type 2 diabetes mellitus. In addition, a cluster of heart disease risk factors seemed clearly related to Type 2 diabetes mellitus (15). This risk-factor clustering, and its association with insulin resistance, led investigators to propose the existence of a unique pathophysiological condition called the “metabolic” (1-3) or “insulin resistance” (12) syndrome. This concept was unified and extended with the landmark publication of Reaven’s 1988 Banting Medal award lecture (16).
