To evaluate the association between adiponectin complexes (high‐molecular‐weight [HMW], middle‐molecular‐weight [MMW], and low‐molecular‐weight [LMW] adiponectin) and diabetes.

We conducted a case‐control study, based on a cohort in Saku, Japan. Among 2565 participants, 300 participants with diabetes and 300 matched controls (430 men and 170 women) were analyzed.

After adjusting for age, physical activity, hypertension, family history, alcohol use, smoking, and menopausal status, total, HMW, and LMW, but not MMW adiponectin levels were inversely associated with diabetes: total adiponectin, odds ratio comparing the highest with the lowest quartiles, 0.46 (95% confidence interval, 0.25–0.82; P for trend = 0.046); HMW, 0.40 (95%CI, 0.22–0.72; P = 0.046); MMW, 1.04 (95%CI, 0.60–1.77; P = 0.81); and LMW, 0.51 (95%CI, 0.29–0.89; P = 0.01). The associations between total and HMW adiponectin and diabetes attenuated after adjustment for BMI (P = 0.15 and 0.13, respectively), but LMW remained (P = 0.04). When stratified by sex, LMW adiponectin levels were associated with diabetes in men only. None of the associations were significant after adjustment for HOMA‐IR.

Decreased LMW, total, and HMW adiponectin levels are associated with diabetes. These associations may be secondary to adiposity or insulin resistance.