Decreased Total and High Molecular Weight Adiponectin Are Independent Risk Factors for the Development of Type 2 Diabetes in Japanese-Americans

Abstract

Adiponectin is a hormone secreted by adipocytes that acts as an antidiabetic adipokine. Adiponectin exists as multimers in plasma, and high molecular weight (HMW) adiponectin is particularly thought to be the active form of the protein. The aim of the study was to assess whether decreased total and HMW adiponectin are independent risk factors for the development of type 2 diabetes. Study subjects were Japanese-Americans enrolled in the Hawaii-Los Angeles-Hiroshima study between 1992 and 2002. Duration of follow-up was an average of 5.4 yr. We investigated 321 men and 445 women who were nondiabetic Japanese-Americans. Glucose tolerance was evaluated according to 1997 American Diabetes Association criteria, and 112 subjects developed type 2 diabetes during the follow-up period. The influence of baseline total and HMW adiponectin on the development of type 2 diabetes was the main outcome measure. Subjects who developed type 2 diabetes had significantly decreased plasma total and HMW adiponectin compared with those who did not develop the disease (P < 0.001, respectively). In a Cox proportional hazards model, both decreased total and HMW adiponectin levels were independent risk factors for the progression to type 2 diabetes after adjusting for sex, age, body mass index, waist-to-hip ratio, homeostasis model assessment, and classification of 75-g glucose tolerance test (hazards ratio: total, 0.600, P = 0.018; HMW, 0.614, P = 0.001, respectively). Dividing tertiles of adiponectin, hazards ratios in the lowest vs. highest tertile were total, 1.787 (95% confidence interval, 1.006-3.173); and HMW, 2.493 (95% confidence interval, 1.342-4.632), after similar adjustments. Decreased total adiponectin is an independent risk factor for the progression to type 2 diabetes in Japanese-Americans. Moreover, HMW adiponectin more closely associates with the progression to type 2 diabetes when compared with total adiponectin.