Total and High-Molecular-Weight Adiponectin and Risk of Incident Diabetes in Older People

• Type of Material: Article
• Authors: Jorge R. Kizer, Weill Cornell Medical College; Alice M. Arnold, University of Washington; David Benkeser, University of Washington; Joachim H. Ix, Veterans Affairs San Diego Healthcare System; Luc Djousse, Brigham and Women's Hospital; Susan J. Zieman, National Institute on Aging; Joshua Barzilay, Emory University; Russell P. Tracy, University of Vermont; Christos S. Mantzoros, Harvard University; David S. Siscovick, University of Washington; Kenneth J. Mukamal, Harvard University
• Language: English
• Date: 2012-02-01
• Publisher: AMER DIABETES ASSOC
• Publication Version: Final Published Version
• Copyright Statement: © 2012 by the American Diabetes Association.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.2337/dc11-1519
• Title of Journal or Parent Work: Diabetes Care
• Volume: 35
• Issue: 2
• Start Page: 415
• End Page: 423
• Grant/Funding Information: Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging.; This work was supported by R01-HL-094555 from the National Heart, Lung, and Blood Institute (NHLBI). The CHS was supported by NHLBI contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, and NHLBI Grant HL-080295, with additional contribution from the National Institute of Neurological Disorders and Stroke.
• Keywords: WOMEN; ENDOCRINOLOGY & METABOLISM; BETA-CELL FUNCTION; Science & Technology; MEN; Life Sciences & Biomedicine; MELLITUS; CARDIOVASCULAR HEALTH; CORONARY-HEART-DISEASE; ADIPOSITY; INSULIN-RESISTANCE; POPULATION; Endocrinology & Metabolism; GLUCOSE
• Research Categories: Biology, Biostatistics; Health Sciences, Pathology

Abstract

OBJECTIVE - To delineate the associations of total adiponectin, high-molecular-weight (HMW) adiponectin, and the HMW-to-total adiponectin ratio with diabetes in older adults. RESEARCH DESIGN AND METHODS - Total and HMW adiponectin were measured in a population-based study of older adults. The relations of total adiponectin, HMW adiponectin, and their ratio with incident diabetes (n = 309) were assessed in 3,802 individuals. RESULTS - Total and HMW adiponectin were highly correlated (r = 0.94). Analysis using cubic splines revealed that the associations between total and HMWadiponectin and new-onset diabeteswere not linear. Specifically, after adjustment for confounders, there were similar inverse relationships for total (hazard ratio per SD 0.49 [95% CI 0.39-0.63]) and HMW adiponectin (0.42 [0.32-0.56] ) with diabetes up to values of 20 and 10 mg/L, respectively, above which the associations plateaued. These associations persisted after adjustment for potential mediators (blood pressure, lipids, C-reactive protein, and homeostasis model assessment of insulin resistance [HOMA-IR]). There was, however, evidence of interaction by HOMA-IR in the lower range of adiponectin, with stronger inverse associations among insulin-sensitive than insulin-resistant participants. HMW-to-total adiponectin ratio showed a linear adjusted association with outcome, but this was abolished by inclusion of mediating variables. CONCLUSIONS - In this older cohort, increasing concentrations of total and HMW adiponectin were associated with comparably lower risks of diabetes, but these associations leveled off with further increases above concentrations of 20 and 10 mg/L, respectively. The more pronounced risk decreases at the lower range among participants without insulin resistance support a role for adiponectin that is independent of baseline hyperinsulinemia, but this will require further investigation.