Association of Thigh Muscle Mass with Insulin Resistance and Incident Type 2 Diabetes Mellitus in Japanese Americans

BACKGROUND: Skeletal muscle plays a major role in glucose metabolism. We investigated the association between thigh muscle mass, insulin resistance, and incident type 2 diabetes mellitus (T2DM) risk. In addition, we examined the role of body mass index (BMI) as a potential effect modifier in this association. METHODS: This prospective study included 399 Japanese Americans without diabetes (mean age 51.6 years) who at baseline had an estimation of thigh muscle mass by computed tomography and at baseline and after 10 years of follow-up a 75-g oral glucose tolerance test and determination of homeostasis model assessment of insulin resistance (HOMA-IR). We fit regression models to examine the association between thigh muscle area and incidence of T2DM and change in HOMA-IR, both measured over 10 years. RESULTS: Thigh muscle area was inversely associated with future HOMA-IR after adjustment for age, sex, BMI, HOMA-IR, fasting plasma glucose, total abdominal fat area, and thigh subcutaneous fat area at baseline (P=0.033). The 10-year cumulative incidence of T2DM was 22.1%. A statistically significant interaction between thigh muscle area and BMI was observed, i.e., greater thigh muscle area was associated with lower risk of incident T2DM for subjects at lower levels of BMI, but this association diminished at higher BMI levels. CONCLUSION: Thigh muscle mass area was inversely associated with future insulin resistance. Greater thigh muscle area predicts a lower risk of incident T2DM for leaner Japanese Americans.