Serum sex hormone–binding globulin, a determinant of cardiometabolic disorders independent of abdominal obesity and insulin resistance in elderly men and women Altan Onat a,b, ⁎ , Gülay Hergenç c , Ahmet Karabulut d , Sinan Albayrak e , Günay Can b , Zekeriya Kaya f a Turkish Society of Cardiology, Istanbul University, 34384 Istanbul, Turkey b Cerrahpaşa Medical Faculty, Istanbul University, 34098 Istanbul, Turkey c Biology Department, Yıldız Technical University, 34349 Istanbul, Turkey d S. Ersek Cardiovascular Surgery Center, Istanbul, Turkey e Cardiology Department of Düzce University Medical Faculty, Düzce, 81620 Istanbul, Turkey f Koşuyolu Heart Hospital, Istanbul, Turkey Received 29 September 2006; accepted 8 May 2007 Abstract Serum sex hormone–binding globulin (SHBG) is related to cardiometabolic disorders; but whether or not this relationship is purely secondary to hyperinsulinemia and/or obesity, which down-regulates SHBG, is unknown. The aim of the study was to investigate the association of SHBG and total testosterone with atherogenic dyslipidemias, metabolic syndrome (MS), and diabetes among predominantly elderly Turkish adults. After appropriate exclusions, 777 randomly selected male and female subjects with available measurements of both variables were eligible and were analyzed cross-sectionally, with diabetic subjects analyzed separately. Free testosterone was calculated. Metabolic syndrome was identified by the modified criteria of the Adult Treatment Panel III. Metabolic syndrome was identified in half the sample, which had a median age of 58 years. The odds of low SHBG concentrations (b45 nmol/L in men, b55 nmol/L in women) for the likelihood of 2 types of dyslipidemias, MS, and diabetes were examined by regression analyses in standard models including age, smoking status, presence of abdominal obesity, and insulin resistance (homeostasis model assessment of insulin resistance). In both sexes, low SHBG was associated independently with high triglyceride/low high-density lipoprotein dyslipidemia and with MS, at significant 2.2- to 4.5-fold odds ratios, independent of waist circumference or homeostasis model assessment of insulin resistance index. Low SHBG among women was additionally associated with the likelihood of hypertriglyceridemia with elevated apolipoprotein B and—at borderline significance—with that of diabetes, again when adjusted for the same confounders. In an elderly population with prevalent MS, low SHBG levels significantly associate with high triglyceride/low high-density lipoprotein dyslipidemia, MS, and, in women alone, diabetes and a dyslipidemia marking small dense low-density lipoprotein particles, all independent of abdominal obesity and insulin resistance. Low SHBG may be an important independent factor for cardiometabolic risk, particularly in women. © 2007 Elsevier Inc. All rights reserved. 1. Introduction The decline in endocrine function in elderly men includes a decrease in total testosterone (TT) concomitant with an increase in sex hormone–binding globulin (SHBG), low- ering further the bioavailable testosterone levels. Hypoan- drogenemia in men and hyperandrogenemia in women are associated with visceral obesity, insulin resistance (IR), low high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, and plasminogen activator inhibitor-1 (PAI-1) [1]. Visceral adipose tissue, insulin levels, and SHBG concentrations seemed to be independent correlates of lipoprotein concentrations in men [2]. In postmenopausal women, SHBG also correlated positively with HDL-C and inversely with insulin after adjustment for adiposity [3]. The sex steroid changes are modified by increasing body mass index (BMI) and waist circumference (WC) as markers of Metabolism Clinical and Experimental 56 (2007) 1356 – 1362 www.elsevier.com/locate/metabol ⁎ Corresponding author. Turkish Society of Cardiology, Istanbul University, 34335 Istanbul, Turkey. Tel.: +90 212 351 6217; fax: +90 212 351 4235. E-mail address: alt_onat@yahoo.com.tr (A. Onat). 0026-0495/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.metabol.2007.05.020