Table 4

Mediating effects of muscle and function on the association of normal weight BMI and mortality

EffectβP value
Model 1Normal weight on mortality risk−0.100.04
Thigh muscle area as mediator
 Model 2Normal weight on muscle−0.18<0.001
 Model 3Muscle on mortality0.25<0.001
 Model 4Normal weight and muscle on mortality
Muscle on mortality0.25<0.001
Normal weight on mortality−0.050.29
Gait speed as mediator
 Model 2Normal weight on gait speed−0.030.58
 Model 3Gait speed on mortality0.21<0.001
 Model 4Normal weight and gait speed on mortality
Gait speed on mortality0.21<0.001
Normal weight on mortality−0.070.13
  • Overweight BMI as referent group vs. normal weight, standardized β. Models adjusted for age, sex, education, duration of diabetes, midlife BMI, waist circumference, total cholesterol, HDL cholesterol, systolic blood pressure, smoking status, hypertension, statin use, diabetes medication type, microalbuminuria, and CRP. The four models tested whether muscle size and gait speed mediate/drive increased mortality risk in normal weight individuals. Model 1 shows that normal weight participants have 0.10 units less of life. Model 2 shows that normal weight participants have 0.18 units less muscle but not significantly different gait speed than overweight participants. Model 3 shows that for a 1-unit increase in muscle, survival increases by 0.25 units (0.21-unit increase for each 1-unit increase in gait speed). When thigh muscle and normal weight are included in a model, the effect of normal weight on mortality is no longer significant, suggesting that the effect is explained in part by thigh muscle (model 4). The 95% CI for thigh muscle was (0.01–0.02) as estimated by the bootstrapping method–confirmed significant mediation (23). When gait speed and normal weight on mortality are included in a model, the effect of normal weight on mortality is no longer significant, but the 95% CI (−0.03 to 0.06) indicated nonsignificant mediation.