Second World Congress on the Insulin Resistance Syndrome: mediators, pediatric insulin resistance, the polycystic ovary syndrome, and malignancy.

This is the second in a series of articles on the Second World Congress on the Insulin Resistance Syndrome, Universal City, California, 18 –20 November 2004. Jacqueline Dekker (Amsterdam, the Netherlands) presented data from the Hoorn Study on the predictive power of insulin resistance syndrome diagnosis, pointing out that the public health role of identifying a person as having insulin resistance syndrome includes the ability to characterize populations to better understand the pathogenesis of adverse outcome, to allow comparison of characteristics of individuals in differing populations, and to serve a communications function in increasing risk awareness, particularly allowing identification of high-risk groups for cardiovascular disease (CVD), cancer, and diabetes. An important question is whether the existing definitions allow optimal diagnosis of high-risk groups. Comparing the Adult Treatment Panel (ATP)-III and American College of Endocrinology (ACE) definitions (1), she noted that the ACE definition starts with high-risk individuals, including non-Caucasian ethnicity, cigarette use, obesity, CVD, hypertension, polycystic ovarian syndrome (PCOS), nonalcoholic fatty liver disease, acanthosis nigricans, history of gestational diabetes or impaired glucose tolerance (IGT), and family history of type 2 diabetes, hypertension, or CVD. The Hoorn Study included 2,484 individuals aged 50 –75 in 1989 –1990, with follow-up examination in 1996 – 1998, and population registry ascertainment of morbidity and mortality. Of 2,162 without diabetes at baseline, there were 429 deaths, 145 with malignancy and 168 with CVD. Insulin resistance syndrome components for men and women included hypertension in 68 and 66%, abdominal obesity in 16 and 40%, impaired fasting glucose in 14 and 9%, IGT in 21 and 18%, high triglycerides in 35 and 29%, and low HDL cholesterol in 28 and 35%, respectively. Twenty-one and 29% of men and women, respectively, satisfied the ATP-III definition and 46 and 42% the ACE definition of insulin resistance syndrome. Despite the greater number satisfying the ACE definition, both criteria predicted adverse outcome. CVD mortality increased 1.8and 1.2fold among ATP-III–positive men and women and 1.5and 1.8-fold among ACE-positive men and women, respectively. For malignancy, risk was increased 1.2and 1.6-fold for those satisfying the ATP-III definition and 0.9 and 1.2-fold for those satisfying the ACE definition. All-cause mortality was increased 1.5fold in both sexes with ATP-III–defined insulin resistance syndrome, whereas it was not significantly increased in men or women satisfying the ACE definition. Both the ATP-III and ACE predicted diabetes. Men satisfying the ACE criteria were 6.9-fold more likely to develop diabetes, and men meeting the ATP-III criteria were 2.9-fold more likely to develop diabetes. Both definitions predicted an approximate sixfold increase in diabetes risk among women. Dekker noted that the number of risk factors is the best predictor of adverse outcome and that other risk factors, such as C-reactive protein (CRP), also provide relevant information. Although the insulin resistance syndrome definitions have identified a large (25– 50%) subset of the population as being positive, the use of these definitions has clearly raised awareness and allowed identification of population characteristics, allocation of funds for health care, and development of CVD prevention strategies.