Low muscle mass is associated with low insulin sensitivity, impaired pancreatic β cell function, and high glucose excursion in nondiabetic nonobese Japanese women

Abstract

AimWe tested whether skeletal muscle mass is associated with insulin sensitivity, pancreatic β-cell function, and postglucose glycemia. MethodsAppendicular skeletal muscle mass (ASM) (relative to body size, %ASM) by DXA, surrogate measures of insulin sensitivity, insulin secretion and the disposition index (insulin sensitivity adjusted insulin secretion: a product of the insulinogenic index and Matsuda insulin sensitivity index) inferred from serum insulin kinetics during a 75 g oral glucose tolerance test (OGTT) were evaluated in 168 young and 65 middle-aged women, whose BMI averaged <23.0 kg/m2 and HbA1c ≦ 5.5 %. ResultsIn two groups of women, %ASM was associated negatively with homeostasis model assessment insulin resistance (HOMA-IR) and 2-h insulin (both p<0.01 or less). In middle-aged women not in young women, %ASM was associated inversely with the Matsuda index (p<0.001). In middle-aged women only, it also showed a positive association with the disposition index (p=0.02) and inverse associations with 1-h and 2-h glucose (both p<0.01) and area under the glucose concentration curve during OGTT (p=0.006). On multivariate linear regression analyses, 2-h insulin emerged as a determinant of %ASM independently of HOMA-IR in young women (standardized β: -0.287, p<0.001, R2=0.077). In middle-aged women, the Matsuda index emerged as a determinant of %ASM (standardized β: 0.476, p<0.001) independently of HOMA-IR, log ODI and AUCg and explained 21.3 % of %ASM variability. Post-glucose glycemia and AUCg were higher and log ODI was lower in middle-aged women with low compared with high %ASM. ConclusionLow skeletal muscle mass (relative to body size) was associated with low insulin sensitivity in young and middle-aged Japanese women who were neither obese nor diabetic. Middle-aged women with low muscle mass had low disposition index, an early marker of inadequate pancreatic β-cell compensation, and hence high glucose excursion. Low skeletal muscle mass may be associated with the development of type 2 diabetes at a much lower BMI in Japanese people.