Pancreatic β-cell function is a stronger predictor of changes in glycemic control after an aerobic exercise intervention than insulin sensitivity

Abstract

Context: Understanding intersubject variability in glycemic control following exercise training will help individualize treatment.

Objective: Our aim was to determine whether this variability is related to training-induced changes in insulin sensitivity or pancreatic β-cell function.

Design, setting, and participants: We conducted an observational clinical study of 105 subjects with impaired glucose tolerance or type 2 diabetes.

Interventions and main outcome measures: Individual subject changes in fitness (VO2max), glycemia (glycosylated hemoglobin, fasting glucose, oral glucose tolerance test), insulin sensitivity (hyperinsulinemic-euglycemic clamp), oral glucose-stimulated insulin secretion (GSIS), and disposition index (DI) were measured following 12 to 16 weeks of aerobic exercise training. Regression analyses were used to identify relationships between variables.

Results: After training, 86% of subjects increased VO2max and lost weight. Glycosylated hemoglobin, fasting glucose, and 2-hour oral glucose tolerance test were reduced in 69%, 62%, and 68% of subjects, respectively, while insulin sensitivity improved in 90% of the participants. Changes in glycemic control were congruent with changes in GSIS such that 66% of subjects had a reduction in first-phase GSIS, and 46% had reduced second-phase GSIS. Training increased first- and second-phase DI in 83% and 74% of subjects. Training-induced changes in glycemic control were related to changes in GSIS (P < .05), but not insulin sensitivity or DI, and training-induced improvements in glycemic control were largest in subjects with greater pretraining GSIS.

Conclusions: Intersubject variability in restoring glycemic control following exercise is explained primarily by changes in insulin secretion. Thus, baseline and training-induced changes in β-cell function may be a key determinant of training-induced improvements in glycemic control.

Trial registration: ClinicalTrials.gov NCT01234155.

Figure 1.

Subjects with impaired glucose tolerance or type 2 diabetes (N = 105) underwent 12 to 16 weeks of moderate-intensity exercise training, 5 days per week, 60 minutes per day. Exercise responsiveness of (A) aerobic fitness, (B) body weight, (C) whole-body adiposity, (D) Hb_A1c (N = 54), (E) fasting glucose, (F) 2-hour OGTT glucose, (G) insulin sensitivity, (H) fasting C-peptide, and (I) 2-hour OGTT C-peptide were measured as the postminus preexercise (Δ) values. Individual subject data points are plotted on the x-axis. Y-axis data above the origin indicate an exercise training-induced increase in that variable; data below the origin represent a training-induced decrease.

Figure 2.

Subjects with impaired glucose tolerance or type 2 diabetes (N = 105) underwent 12 to 16 weeks of moderate-intensity exercise training, 5 days per week, 60 minutes per day. Exercise responsiveness of first-phase oral GSIS (A) and DI (B), and second-phase GSIS (C) and DI (D) were measured as the postminus preexercise (Δ) values. Individual subject data points are plotted on the x-axis. Y-axis data above the origin indicate an exercise training-induced increase in that variable; data below the origin represent a training-induced decrease. First-phase GSIS is reported as the area under the serum C-peptide response curve during the first 30 minutes following the ingestion of 75 g glucose. Second-phase GSIS is reported as the area under the C-peptide curve from 30 to 120 minutes after glucose ingestion. DI is calculated as the product of GSIS and insulin sensitivity.

Figure 3.

Subjects with impaired glucose tolerance or type 2 diabetes (N = 105) underwent 12 to 16 weeks of moderate-intensity exercise training, 5 days per week, 60 minutes per day. Relationships between variables were analyzed by linear regression. (A) and (B) demonstrate that a greater training-induced increase in first- and second-phase GSIS (x-axis) was related to a greater training-induced decrease in 2-hour plasma glucose measured during OGTT (y-axis). (C) and (D) indicate that larger preintervention first- and second-phase GSIS (x-axis) were associated with larger training-induced improvements in oral glucose tolerance (y-axis). (E) and (F) show that poorer preintervention glycemic control, as indicated by high HbA_1c (x-axis), was correlated with poorer training-induced improvements in the DI (y-axis). First-phase GSIS is measured as the area under the serum C-peptide response curve during the first 30 minutes following the ingestion of 75 g glucose. Second-phase GSIS is measured as the area under the C-peptide curve from 30 to 120 minutes after glucose ingestion. DI is calculated as the product of GSIS and insulin sensitivity.