Degradation in insulin sensitivity with increasing severity of the metabolic syndrome in obese postmenopausal women A. D. Karelis, 1 J.-F. Henry, 1 D. H. St-Pierre, 1 D. Prud’homme 2 and R. Rabasa-Lhoret 1 1 Department of Nutrition, Universite´ de Montre´al, Montreal, Quebec, Canada 2 School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada Aim: We investigated the relationship between insulin sensitivity and the graded increase in the number of features of the metabolic syndrome in a cross-sectional sample of obese postmenopausal women. We hypothesized that insulin sensitivity would deteriorate with an increased number of metabolic syndrome phenotypes. Methods: Insulin sensitivity was measured in 75 obese postmenopausal women (age: 57.3  5.3 years; BMI: 32.8  4.5 kg/m 2 ) by using both the hyperinsulinaemic–euglycaemic clamp and the homeostasis model assessment (HOMA-IR). Features of the metabolic syndrome included visceral fat (>130 cm 2 ), HDL-cholesterol (<1.29 mmol/l), fasting triglycerides (1.7 mmol/l), blood pressure (130/85 mmHg) and fasting glucose (6.1 mmol/l). Participants were classified into three categories based on the presence of metabolic syndrome phenotypes: 0–1 vs. 2 vs. 3 features of the metabolic syndrome. Results: We found that insulin sensitivity decreased in a graded fashion (12.19  3.2 vs. 11.80  2.3 vs. 9.29  2.6 mg/min/FFM) and HOMA-IR increased in a similar manner (2.95  1.1 vs. 3.28  1.3 vs. 4.65  2.2), as the number of features of the metabolic syndrome increased from 0–1 to 3. When insulin sensitivity was statistically adjusted for visceral fat (as measured by computed tomography) and plasma triglycerides, the differences among groups were abolished. Conclusions: These findings suggest that a decreased insulin sensitivity is associated with increased features of the metabolic syndrome in obese postmenopausal women and that visceral fat as well as plasma triglyceride accumulation might be potential mediators of this relationship. Keywords: HOMA-IR, hyperinsulinaemic-euglycaemic clamp, triglycerides, visceral fat Received 3 December 2004; returned for revision 11 February 2005; revised version accepted 23 February 2005 Introduction The metabolic syndrome is a cluster of metabolic risk factors that comprises hyperglycaemia, dyslipidaemia, abdominal obesity and hypertension [1]. Ford et al. [2] reported that approximately 22% of US adults have the metabolic syndrome. Moreover, women are disproportion- ately affected, because 43% of postmenopausal women are classified as having the metabolic syndrome [2]. The relationship of insulin resistance with the patho- physiology of the metabolic syndrome remains unclear. Most patients with multiple metabolic risk factors are insulin-resistant, which is a known predictor of cardio- vascular disease [3–5]. This observation has led to the hypothesis that insulin resistance could be associated with the development of the metabolic syndrome [6]. In support of this concept, two reviews have suggested that a decrease in insulin sensitivity could precede and con- tribute to the development of the metabolic syndrome [7,8]. Interestingly, a recent study examined the associa- tion between insulin sensitivity and the individual Correspondence: Antony D. Karelis, Department of Nutrition, Universite´ de Montre´al, Montreal, Quebec, Canada. E-mail: antony.karelis@umontreal.ca SHORT REPORT doi: 10.1111/j.1463–1326.2005.00503.x 336 Diabetes, Obesity and Metabolism, 8, 2006, 336–341 # 2005 Blackwell Publishing Ltd