Original Article Sex-Discordant Associations With Adiponectin Levels and Lipid Profiles in Children Ken K. Ong, 1,2 Jan Frystyk, 3 Allan Flyvbjerg, 3 Clive J. Petry, 2 the Avon Longitudinal Study of Parents and Children Study Team, 4 Andy Ness, 4 and David B. Dunger 2 In adults, lower circulating levels of the adipocyte-derived hormone adiponectin are associated with obesity, type 2 diabetes, and cardiovascular disease risks. Its use as a risk marker in children is less clear. In 839 children aged 8 years from a representative birth cohort, circulating adi- ponectin levels were associated with body weight, BMI, waist circumference, and fasting and 30-min insulin levels, but the associations were opposite in boys, with positive associations, and girls, with inverse associations (P  0.008 – 0.00001 for interaction with sex). Girls had overall higher adiponectin, higher total cholesterol, lower HDL cholesterol, and higher triglyceride levels than boys, even after adjustment for BMI. With increasing BMI, girls showed steeper declines in HDL cholesterol (P  0.01 for interaction) and adiponectin levels (P  0.0005 for inter- action) and a steeper increase in triglyceride levels (P  0.009 for interaction) compared with boys. In conclusion, plasma adiponectin is not a simple marker of central fat and insulin sensitivity in children. With increasing BMI, decreasing adiponectin levels in girls could contribute to their faster deterioration in lipid profiles in comparison with boys. Our data suggest a complex age- and sex-related regulation of adiponectin secretion or clearance. Diabetes 55:1337–1341, 2006 A diponectin is an adipokine with potent insulin- sensitizing properties in mice and humans (1,2). In adult populations, lower circulating adi- ponectin levels are associated with insulin re- sistance and lower HDL cholesterol levels and predict type 2 diabetes and cardiovascular disease risks (3,4). How- ever, the strong inverse relationship observed between circulating adiponectin levels and measures of both body fat mass and insulin resistance is counterintuitive, consid- ering that it derives exclusively from fat cells (5). In contrast, most other adipokines, such as leptin and visfa- tin, show positive relationships with adiposity (6,7). The regulation of circulating adiponectin levels is com- plex. It is secreted from fat cells in one of three main forms: a low–molecular weight 67-kDa hexamer, a medi- um–molecular weight 136-kDa hexamer, and a high–mo- lecular weight 300-kDa hexamer complex (8). Current assays detect all three molecular forms of circulating adiponectin but do not yet distinguish between each specific form. A number of hormones may influence adi- ponectin secretion (6), including variable effects of insulin on adiponectin mRNA expression and protein levels (9 – 11). In some childhood populations, as in adults, lower adiponectin levels have been proposed as a marker of obesity and risk of developing type 2 diabetes (12,13). However, in the newborn, adiponectin levels are around twofold higher and show positive associations with birth weight and BMI (14 –16). Furthermore, in newborns, adi- ponectin levels increase with higher leptin levels and gestational age, suggesting a positive relationship with the development of fetal adiposity (15,17). Adiponectin levels decrease during early childhood, and this is related to the rate of postnatal weight gain (18,19). A reversal in the direction of association (from positive to negative) be- tween adiponectin and adiposity must therefore occur at some time during childhood (14). To assess the direction of associations between adiponectin levels and adiposity, insulin sensitivity, and blood lipid levels in children, we measured its circulating levels in a well-characterized representative birth cohort at age 8 years. RESEARCH DESIGN AND METHODS The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospec- tive study of 14,541 pregnancies recruited from all pregnancies in three Bristol-based District Health Authorities with expected dates of delivery between April 1991 and December 1992 (http://www.alspac.bris.ac.uk). All children were measured at birth and at age 7 years; details of measurements have been previously described (20,21). The new data in this report relate to fasting adiponectin levels and lipid profiles at age 8 years. Blood samples and anthropometry at age 8 years. A total of 885 unselected full-term, singleton birth, 8-year-old ALSPAC children attended a substudy of fasting and 30-min postoral glucose (1.75 g/kg, max. 75 g) blood sampling and measurements of body weight, height, and waist circumference, as previously described (22). Insulin and glucose levels were measured on fasting and 30-min venous blood samples. We measured plasma adiponectin levels in fasting plasma samples at this age 8 –year visit in 839 children (449 males). These children did not differ from other ALSPAC children with regard to size at birth or at age 7 years; compared with a current U.K. growth reference (23), they had a mean  SD birth weight SD score of 0.01  1.04 and a BMI SD score at 7 years of age of 0.17  1.04. Only 16 children were nonwhite (1.9%) and had no differences in adiponectin, BMI, or insulin sensitivity compared with the other children. From the 1 Medical Research Council Epidemiology Unit, Strangeways Re- search Laboratory, Cambridge, U.K., the 2 Department of Paediatrics, Univer- sity of Cambridge, Addenbrooke’s Hospital, Cambridge, U.K.; 3 The Medical Research Laboratories Clinical Institute and Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus, Denmark; the 4 Unit of Pediatric and Perinatal Epidemiology, Department of Community Based Medicine, University of Bristol, Bristol, U.K. Address correspondence and reprint requests to Dr. Ken K. Ong, MRC Epidemiology Unit, Strangeways Research Laboratory, Wort’s Causeway, Cambridge CB1 8RN U.K. E-mail: ken.ong@mrc-epid.cam.ac.uk. Received for publication 29 September 2005 and accepted in revised form 3 February 2006. Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org. ALSPAC, Avon Longitudinal Study of Parents and Children. DOI: 10.2337/db05-1272 © 2006 by the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. DIABETES, VOL. 55, MAY 2006 1337