BACKGROUND: Although evidence about skeletal muscle mass loss and type 2 diabetes risk has accumulated, little information is available on the combined effect of skeletal muscle mass and abdominal obesity on type 2 diabetes. We examined whether skeletal muscle mass and abdominal obesity were synergistically associated with the prevalence of type 2 diabetes. METHODS: Skeletal muscle mass and waist circumference (WC) were measured in 1515 Japanese aged 40-69 years. Relative muscle mass was calculated as percentage of total skeletal muscle mass in body weight (SMM%). Type 2 diabetes was identified as fasting serum glucose ≥7.0 mmol/L (126 mg/dL), non-fasting serum glucose ≥11.1 mmol/L (200 mg/dL), hemoglobin A1c ≥ 6.5%, and/or diabetes medication use. RESULTS: The multivariable-adjusted odds ratio (OR) of prevalent diabetes from the lowest to third quartiles of SMM% compared to the highest quartile was gradually higher in both sexes. The association between a high WC and prevalent diabetes was similar. The multivariable-adjusted OR (95% confidence intervals) for the prevalence of type 2 diabetes in the low skeletal muscle mass/high WC group was 3.19 (1.78-5.71) for men and 4.46 (2.09-9.51) for women compared with the high skeletal muscle mass/low WC group. The relative excess risk due to interaction was 2.2 (0.5-3.9) in men and 2.8 (0.2-5.3) in women for an excess burden of type 2 diabetes for low skeletal muscle mass and high WC. CONCLUSIONS: Low skeletal muscle mass and abdominal obesity were synergistically associated with presence of type 2 diabetes. This article is protected by copyright. All rights reserved.