Association between cardiorespiratory fitness and the determinants of glycemic control across the entire glucose tolerance continuum

Abstract

Objective: Cardiorespiratory fitness (VO2max) is associated with glycemic control, yet the relationship between VO2max and the underlying determinants of glycemic control is less clear. Our aim was to determine whether VO2max is associated with insulin sensitivity, insulin secretion, and the disposition index, a measure of compensatory pancreatic β-cell insulin secretion relative to insulin sensitivity, in subjects representing the entire range of the glucose tolerance continuum.

Research design and methods: A cohort of subjects (N = 313) with heterogeneous age, sex, BMI, and glycemic control underwent measurements of body composition, HbA1c, fasting glucose, oral glucose tolerance (OGTT), and VO2max. OGTT-derived insulin sensitivity (SiOGTT), glucose-stimulated insulin secretion (GSISOGTT), and the disposition index (DIOGTT) (the product of SiOGTT and GSISOGTT) were measured, and associations between VO2max and these determinants of glycemic control were examined.

Results: A low VO2max was associated with high HbA1c (r = -0.33), high fasting glucose (r = -0.34), high 2-h OGTT glucose (r = -0.33), low SiOGTT (r = 0.73), and high early-phase (r = -0.34) and late-phase (r = -0.36) GSISOGTT. Furthermore, a low VO2max was associated with low early- and late-phase DIOGTT (both r = 0.41). Interestingly, relationships between VO2max and either glycemic control or late-phase GSISOGTT deteriorated across the glucose tolerance continuum.

Conclusions: The association between poor cardiorespiratory fitness and compromised pancreatic β-cell compensation across the entire glucose tolerance continuum provides additional evidence highlighting the importance of fitness in protection against the onset of a fundamental pathophysiological event that leads to type 2 diabetes.

Figure 1

Cardiorespiratory fitness is associated with markers of glycemic control. VO_2max was measured during incremental workload and exhaustive aerobic exercise in subjects representative of a heterogeneous population with respect to age, BMI, adiposity, and glucose tolerance status (white circles, NGT; light-gray squares, IGT; and dark-gray triangles, T2D). Regression analysis demonstrated inverse curvilinear log-log relationships between VO_2max and HbA_1c (log₁₀y = −0.14 log₁₀x + 0.98) (A), fasting glucose (log₁₀y = −0.17 log₁₀x + 1.03) (B), and 2-h glucose during OGTT (log₁₀y = −0.39 log₁₀x + 1.55) (C). Solid and dotted lines represent the regression curves and 95% CI, respectively, and show unadjusted data.

Figure 2

Cardiorespiratory fitness is associated with Si_OGTT, GSIS_OGTT, and DI_OGTT. VO_2max was measured during incremental workload and exhaustive aerobic exercise in subjects representative of a heterogeneous population with respect to age, BMI, adiposity, and glucose tolerance status (white circles, NGT; light-gray squares, IGT; and dark-gray triangles, T2D). VO_2max was directly associated with Si_OGTT (y = 0.00117x + 0.0119) (A) but had an inverse curvilinear log-log relationship with early-phase (log₁₀y = −0.39 log₁₀x + 5.18) (B) and late-phase (log₁₀y = −0.42 log₁₀x + 6.07) (C) GSIS_OGTT. Finally, there were direct linear relationships between VO_2max and early-phase (y = 27.8x + 916) (D) and late-phase (y = 200x + 5,966) (E) DI_OGTT, a measure of pancreatic β-cell insulin secretory compensation for changing insulin sensitivity. Solid and dotted lines represent the regression curves and 95% CIs, respectively, and show unadjusted data.