Highlights From The First World Congress on the Insulin Resistance Syndrome

Zachary T. Bloomgarden, MD


January 29, 2004

In This Article

Definitions of the IRS

Richard C. Pasternak, MD, Harvard Medical School, Boston, Massachusetts, discussed the deliberations that led the National Cholesterol Education Program (NCEP) ATP III panel to propose its definition of the metabolic syndrome.[35,36] Clinical trials show evidence for modification of atherogenic dyslipidemia, for blood pressure treatment, and for aspirin administration. Primary management goals should be the reversal of the root causes of obesity and physical inactivity. Intensified LDL lowering should be considered. In the Atherosclerosis Risk in Communities Study, 52% of persons with the metabolic syndrome and 23% of those without the metabolic syndrome had increased carotid artery intima-media thickness. The association of CRP with atherosclerotic risk in the West of Scotland Coronary Prevention Study was additive to the presence of metabolic syndrome.[37]

Daniel Einhorn, MD, Scripps Whittier Institute for Diabetes, San Diego, California, gave a similar assessment of the ACE/AACE consensus definition of the IRS,[38,39] which differs from ATP III in the following ways:

  • It focuses on the IRS rather than on CVD;

  • It excludes persons with type 2 diabetes;

  • It recognizes the limitations of the fasting glucose and the usefulness of the 2-hour post-challenge glucose; and

  • It views obesity, based either on BMI or waist circumference, as a risk factor rather than as a criterion.

Factors that increase the likelihood of the IRS include CVD; hypertension; PCOS; NAFLD; acanthosis nigricans; non-Caucasian ethnicity; sedentary lifestyle; age > 40; a history of gestational diabetes or glucose intolerance; and a family history of type 2 diabetes, hypertension, or CVD. Suggested targets for reducing CVD risk are LDL < 100 mg/dL, triglyceride < 150 mg/dL, and BP < 130/80 mm Hg.

Jacqueline M. Dekker, PhD, Institute for Research in Extramural Medicine, Vrije Universiteit, Amsterdam, The Netherlands, reviewed the working definitions of the IRS proposed by the World Health Organization (WHO),[40,41] the NCEP ATP III, the ACE, and the European Group for the Study of Insulin Resistance (EGIR) ( Table ).[42]

In a study[43] of 1209 Finnish men aged 42-60 years, the 10-year CVD risk was 2.1- and 2.5-fold increased with the ATP III and WHO IRS definitions, respectively. In the Botnia Dietary Study,[44] there was a 1.8-fold increase in risk in persons satisfying the WHO IRS criteria.

Dr. Dekker presented an analysis of the Hoorn study of 2484 persons, begun in 1989 with persons then aged 50-75 years.[40] Among both men and women, those with ATP III IRS were more likely to have hypertension, hypertriglyceridemia, low HDL cholesterol, and higher glucose, insulin, and waist circumference. Nineteen percent of men and 26% of women in the study had IRS by the ATP III criteria; 32% and 17%, respectively, had IRS by the WHO criteria; 19% and 26%, respectively, had IRS by the EGIR criteria; and 35% and 33%, respectively, had IRS by the ACE criteria, with 60% to 80% agreement between the various definitions. Among men, those having IRS according to either the ATP III or ACE criteria had a doubling of risk for CVD, while those with IRS according to the WHO and EGIR had a 1.5-fold increased risk. Among women, the associations were less strong: those with IRS by the ATP III criteria had twice the risk of CVD without increase in fatal CVD; those satisfying the ACE criteria had doubling of nonfatal CVD and a 1.5-fold increase in fatal CVD. The strengths of association were weaker among women for the WHO and EGIR criteria.

Persons with IRS based on the ACE guidelines who did not have recognized CVD risk factors did not in fact have increased CVD risk, while risk increased (as would be expected) with the number of risk factors. Other studies have shown that the IRS was not an independent predictor if individual risk factors were included in the analysis.[45] Using the Hoorn study data, among men, high insulin predicted a 1.5-fold increase in CVD, increased waist circumference predicted a doubling, and hypertension predicted a 2-3-fold increase in risk. Among women, high insulin and waist circumference predicted risk of nonfatal but not fatal CVD, and both low HDL and high triglyceride levels were significant factors predicting both fatal and nonfatal CVD.