The glucose stimulus-response curve of the β-cell in physically trained humans, assessed by hyperglycemic clamps

In order to examine the effect of habitual exercise on β-cell responses over a wide range of plasma glucose levels, plasma insulin and C-peptide responses to 212-hour hyperglycemic clamps at 7.5, 10, and 15 mmol/L glucose were assessed in six trained athletes and six age- and weight-matched sedentary controls. Athletes were significantly fitter than controls (estimated maximal oxygen uptake [VO2 max] mean 44 v 30 mL · kg−1 · min−1, P < .05) and were more sensitive to insulin as assessed by dividing the mean glucose infusion rate over the last 20 minutes of the clamp by the steady-state plasma insulin (mean 0.44 v 0.19 mg · min−1 · kg−1 · nmol−1 · L, respectively, P < .01). Plasma C-peptide responses were lower in the athletes, both fasting (geometric mean 0.28 v 0.62 nmol/L, P < .05), and at the end of all clamps (at 7.5, 10, and 15 mmol/L plasma glucose, respectively, 0.65 v 1.43, 1.25 v 2.85, and 2.40 v 4.46 nmol/L each, P < .05). First-phase plasma C-peptide responses were lower in the athletes at the 10 and 15 mmol clamp levels. The slope of the glucose-C-peptide stimulus-response curve was approximately linear over the range examined, the slope being significantly shallower in athletes than controls for both first phase (P < .01) and second phase (P < .01). Plasma insulin responses were similar to C-peptide responses. The attenuation of β-cell responsiveness over a wide glucose range may be an adaptation to the enhanced peripheral insulin sensitivity seen in athletes.