Fat distribution influences the cardio-metabolic profile in a clinically healthy European population E. Bobbioni-Harsch * , Z. Pataky * , V. Makoundou * , M. Kozakova † , J. Dekker ‡ and A. Golay * on the behalf of the RISC Investigators * Geneva University Hospital, Geneva, Switzerland, † University of Pisa, Pisa, Italy, ‡ VU University Medical Center, Amsterdam, The Netherlands ABSTRACT Background and aims Waist and hip circumferences are largely influenced by Fat Mass and several other determinants. To evaluate the specific effects of a preferential fat distribution, we corrected the waist and hip circumferences for all their determinants. We then examined the association between fat distribution and several cardio-metabolic parameters in a clinically healthy population. Subjects and methods In a subgroup of 625 females (F) and 490 males (M) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, we evaluated insulin sensitivity by hyperinsulinae- mic euglycaemic clamp and intima-media thickness (IMT) of the common (CCA) and internal (ICA) carotid artery by ultrasound imaging. Waist and hip circumferences were adjusted for age, height, fat and fat-free mass; in males, waist was also adjusted by hip and vice versa. Results Both F and M with enlarged waist showed significantly increased plasma insulin, C-peptide, total cholesterol, non-high density lipoprotein-cholesterol, low density lipoprotein cholesterol and triglycerides, when compared with subjects with a smaller waist circumference. Males also showed lower glucose uptake and higher heart rate and ICA-IMT. A larger hip in both females and males was linked to a significantly greater inhibition of free fatty acids during the clamp test. Conclusion Adjustment of waist circumference for its determinants permits the detection of early impairment of cardiovascular function and of glucose and lipid metabolism in a clinically healthy population, in particular in normal body weight subjects. Enlarged hip adjusted values are associated with greater insulin sensitivity. Keywords Cardiovascular disease, fat distribution, glucose and lipid metabolism. Eur J Clin Invest 2009; 39 (12): 1055–1064 Introduction Obesity is a significant and growing health problem in industri- alized societies and an important risk factor for cardiovascular and metabolic diseases [1]. Increased body fat has been associ- ated with a broad spectrum of cardio-metabolic disturbances. However, several papers demonstrated that not all obese indi- viduals display a clustering of metabolic and ⁄ or cardiovascular risk factors [2–4] and, on the other hand, subjects with normal or only slightly increased body weight can display some of the metabolic or cardiovascular risk factors [5,6]. The reliability of body mass index (BMI) as a predictor of an unfavourable cardiovascular profile has been recently ques- tioned [5,7]. Romero-Corral et al. showed that a BMI ‡ 30 kg m )2 had poor sensitivity (43%) for diagnosis of excess fat mass because of its inability to discriminate between body fat and lean mass [5]. Extensive data have confirmed that fat distribution could play a more important role in the obesity-related cardio-meta- bolic complications than the BMI itself [8,9]. Waist circumfer- ence (WC) and waist-to-hip ratio (WHR) are widely used as indirect measures of abdominal or central obesity with prede- fined cut-off values [10,11]. However, the WC is influenced by adipose tissue accumulated both at intra-abdominal and subcu- taneous regions [12]. In addition to fat mass, WC is determined by several other factors, such as gender, age, height and fat-free mass. For this reason, when using the waist absolute value, it is difficult to differentiate the effects of WC from those of fat mass extent per se as well as the impact of the above-mentioned other influencing factors. Some authors have suggested investigating the influence of WC after correction for the BMI [13–15]. How- ever, height and weight are not the only determinants of waist European Journal of Clinical Investigation Vol 39 1055 DOI: 10.1111/j.1365-2362.2009.02211.x ORIGINAL ARTICLE