Higher serum myostatin levels are associated with lower insulin sensitivity in adults with overweight/obesity

Myostatin inhibition improves insulin sensitivity in preclinical and clinical models; however, studies investigating the relationship between serum myostatin levels and insulin sensitivity are discrepant. Sensitive and specific myostatin LC-MS/MS assays are now available to accurately assess serum myostatin level in vivo. We sought to determine whether higher serum myostatin levels are independently associated with lower insulin sensitivity in adults with overweight/obesity. Participants included 74 adults, 20-65 years old, BMI ≥25 kg/m² without type 2 diabetes. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry; visceral adipose tissue (VAT) was measured by computed tomography. Main outcome measures were serum myostatin levels (LC-MS/MS) and insulin sensitivity (Matsuda index). Mean age was 48 ± 12 years, and BMI was 33.1 ± 5.6 kg/m² (mean ± SD). Men had higher mean serum myostatin levels versus women (8.3 ± 1.9 vs. 7.2 ± 1.9 ng/mL, p = 0.01) and higher serum myostatin levels were associated with higher ALM (R = 0.34, p = 0.003). Higher serum myostatin levels were associated with lower Matsuda index (R = -0.44, p = 0.0004), which remained significant after controlling for BMI, VAT, ALM, and sex. In conclusion, higher serum myostatin levels are independently associated with lower insulin sensitivity in adults with overweight/obesity and may be a marker of or play a mechanistic role in the development of insulin resistance.