Insulin-mediated muscle microvascular perfusion and its phenotypic predictors in humans

Kaitlin M Love, Linda A Jahn, Lee M Hartline, James T Patrie, Eugene J Barrett, Zhenqi Liu, Kaitlin M Love, Linda A Jahn, Lee M Hartline, James T Patrie, Eugene J Barrett, Zhenqi Liu

Abstract

Insulin increases muscle microvascular perfusion and enhances tissue insulin and nutrient delivery. Our aim was to determine phenotypic traits that foretell human muscle microvascular insulin responses. Hyperinsulinemic euglycemic clamps were performed in 97 adult humans who were lean and healthy, had class 1 obesity without comorbidities, or controlled type 1 diabetes without complications. Insulin-mediated whole-body glucose disposal rates (M-value) and insulin-induced changes in muscle microvascular blood volume (ΔMBV) were determined. Univariate and multivariate analyses were conducted to examine bivariate and multivariate relationships between outcomes, ΔMBV and M-value, and predictor variables, body mass index (BMI), total body weight (WT), percent body fat (BF), lean body mass, blood pressure, maximum consumption of oxygen (VO2max), plasma LDL (LDL-C) and HDL cholesterol, triglycerides (TG), and fasting insulin (INS) levels. Among all factors, only M-value (r = 0.23, p = 0.02) and VO2max (r = 0.20, p = 0.047) correlated with ΔMBV. Conversely, INS (r = - 0.48, p ≤ 0.0001), 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) correlated with M-value. While both ΔMBV (p = 0.045) and TG (p = 0.03) provided significant predictive information about M-value in the multivariate regression model, only M-value was uniquely predictive of ΔMBV (p = 0.045). Thus, both M-value and VO2max correlated with ΔMBV but only M-value provided unique predictive information about ΔMBV. This suggests that metabolic and microvascular insulin responses are important predictors of one another, but most metabolic insulin resistance predictors do not predict microvascular insulin responses.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Bivariate relationships between M-value and prediction variables. (A) Pearson correlations between M-value and subject characteristics. The vertical lines indicate the 95% confidence interval for the correlation coefficient. (B–F) Relationships between M-value and individual predictor variables. The red lines represent the ordinary least squares linear regressions. (G) Relationship between M-value and cardiorespiratory fitness. ΔMBV, insulin-mediated change in muscle microvascular blood volume; BMI, body mass index; BP, blood pressure; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; TRI, triglycerides; VO2max, maximum consumption of oxygen (mL/kg/min); VO2 fitness, level of cardiorespiratory fitness by tertile. Plotting symbols: Healthy°, Obese˟, Type 1 diabetesΔ.
Figure 2
Figure 2
Bivariate relationships between ΔMBV and prediction variables. (A) Pearson correlations between ΔMBV and subject characteristics. The vertical lines indicate the 95% confidence interval for the correlation coefficient. (B–F) Relationships between ΔMBV and individual predictor variables. The red lines represent the ordinary least squares linear regressions. (G) Relationship between ΔMBV and cardiorespiratory fitness. BMI, body mass index; BP, blood pressure; HDL, high-density lipoprotein cholesterol; LDL, low density lipoprotein cholesterol; TRI, triglycerides; VO2max, maximum consumption of oxygen (mL/kg/min); VO2 fitness, level of cardiorespiratory fitness by tertile. Plotting symbols: Healthy°, Obese˟, Type 1 diabetesΔ.
Figure 3
Figure 3
Sex comparisons between M-values corrected for lean body mass (A) and ΔMBV (B). P-values represent unpaired t-tests with Welch’s correction.

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