Insulin recruits muscle microvasculature to enhance insulin and nutrient delivery. Insulin resistance (IR) blunts this microvascular action. While metabolic and microvascular IR usually coexist, and phenotypic traits which foretell metabolic IR are well established, those which predict microvascular IR are unknown. To test whether metabolic IR and its associated traits predict microvascular IR, we performed euglycemic insulin clamps (1 mU/kg/min) in healthy lean (n= 57), healthy obese (n=15) and lean type 1 diabetes subjects (T1D) (n=25), and tested parametric correlations and a multivariate model ANOVA. We measured insulin-mediated whole body glucose disposal (M-value) and insulin-induced changes in muscle microvascular blood volume (ΔMBV) by contrast-enhanced ultrasound. Predictor variables included body mass index (BMI), total body weight (WT), percent body fat (BF), lean body mass, blood pressure, maximal rate of oxygen consumption (VO2max), and plasma levels of LDL cholesterol (LDL-C), HDL cholesterol, triglycerides (TG), fasting insulin (INS) and free fatty acids.
A total of 97 subjects were included (mean age 25.4±6.8, 47% women) in the analyses. Among all factors, only M-value (r=0.23, p=0.023) and VO2max (r=0.20, p=0.047) correlated with ΔMBV. Conversely, INS (r=-0.59, P≤0.001), BF (r=-0.54, p≤0.001), VO2max (r=0.5, p≤0.001), BMI (r=-0.40, p<0.001), WT (r=-0.33, p=0.001), LDL-C (r=-0.26, p=0.009), TG (r=-0.25, p=0.012), as well as ΔMBV correlated with M-value. While both ΔMBV (p=0.045) and TG (p=0.037) independently predicted M-value, only M-value independently predicted ΔMBV (p=0.045).
In conclusion, both M-value and VO2max correlated with but only M-value independently predicted microvascular IR. This suggests that, while metabolic and microvascular IR are important predictors of one another, most phenotypic predictors of metabolic IR do not predict microvascular IR.
K. Love: None. L. Jahn: None. L. Hartline: None. E. Barrett: None. Z. Liu: None.
American Diabetes Association (1-17-ICST-059 to Z.L.); National Institutes of Health (1F32DK121431-01)