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Title: Adiponectin and the mediation of HDL cholesterol change with improved lifestyle: The Look AHEAD Study

Author
item BELALCAZAR, MARIA - University Of Texas Medical Branch
item LANG, WEI - Wake Forest University School Of Medicine
item HAFFNER, STEVEN - University Of Texas Health Science Center
item HOOGEVEEN, RON - Baylor College Of Medicine
item PI-SUNYER, XAVIER - Columbia University - New York
item SCHWENKE, DAWN - Arizona State University
item BALASUBRAMANYAM, ASHOK - Baylor College Of Medicine
item TRACY, RUSSELL - University Of Vermont
item KRISKA, ANDREA - University Of Pittsburgh
item BALLANTYNE, CHRISTIE - Baylor College Of Medicine
item FOREYT, JOHN - Children'S Nutrition Research Center (CNRC)

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/5/2012
Publication Date: 9/5/2012
Citation: Belalcazar, M.L., Lang, W., Haffner, S.M., Hoogeveen, R.C., Pi-Sunyer, X., Schwenke, D.C., Balasubramanyam, A., Tracy, R.P., Kriska, A.P., Ballantyne, C.M., Foreyt, J.P., The Look Ahead Research Group. 2012. Adiponectin and the mediation of HDL cholesterol change with improved lifestyle: The Look AHEAD Study. Journal of Lipid Research. 53(12):2726-2733.

Interpretive Summary: Adipose (fat) tissue dysfunctions have been found to play a large role in the development of many of the metabolic abnormalities often characteristic of type 2 diabetes (T2D). Nearly 1 in 10 Americans are diagnosed with diabetes, and of these individuals cardiovascular disease (CVD) is the largest single cause of death and a significant cause of decreased life expectancy. Adiponectin is a marker of adipose health and often found in large quantities in circulation. However, adiponectin is often found in decreased amounts in obese individuals with T2D. This study investigated whether an intensive lifestyle intervention (ILI) designed to promote weight loss would have an effect on adiponectin levels and mediate an increase in low levels of HDL-cholesterol (HDL-C) to facilitate heart health. Analyses were performed for adiponectin and its high-molecular-weight (HMW) and non-HMW fractions. The findings from this study supported the contribution of both HMW- and non-HMW-adiponectin to the improvement of HDL-C levels with ILI programs and may lead to lower instances of CVD and cardiovascular events in individuals with T2D. These findings are important to the research community for increased understanding of adiponectin on human health.

Technical Abstract: Adipose tissue dysfunction plays a key role in the development of the metabolic abnormalities characteristic of type 2 diabetes (T2DM) and participates actively in lipid metabolism. Adiponectin, found abundantly in circulation and a marker of adipose health, is decreased in obese persons with T2DM. We investigated whether the changes in adiponectin with an intensive lifestyle intervention (ILI) for weight loss could potentially mediate the increase in low HDL-cholesterol (HDL-C) with ILI. Adiponectin and its fractions were determined using an ELISA with selective protease treatment in 1,397 participants from Look AHEAD, a trial examining whether ILI will reduce cardiovascular events in overweight/obese subjects with T2DM when compared with a control arm, diabetes support and education (DSE). Multivariable regression and mediational analyses were performed for adiponectin and its high-molecular-weight (HMW) and non-HMW fractions. ILI increased baseline HDL-C by 9.7% and adiponectin by 11.9%; changes with DSE were 1.3% and 0.2%, respectively (P < 0.0001). In a model including changes in weight, fitness, triglycerides, and glucose control and that adjusted for demographics and medical history, adiponectin changes remained significantly associated with HDL-C change. Data supported the contribution of changes in both HMW- and non-HMW-adiponectin to the improvement in HDL-C with ILI.