Impaired glucose tolerance after endurance exercise is associated with reduced insulin secretion rather than altered insulin sensitivity

Paired frequently sampled intravenous glucose tolerance tests (FSIGT) were performed on five highly trained athletes within 2 hours of completing a 6-day ultramarathon run (E) and after 2 weeks of complete rest (R). Severe exercise increased free fatty acid (FFA) levels (E 1.2 ± 0.16 v 0.42 ± 0.07 mmol/L, P < .01) and norepinephrine levels (E 573 ± 141 v 224 ± 33 pg/mL, P < .01), with only moderate reductions in glucose tolerance (glucose disappearance [K_g] E 1.06 ± 0.2 v R 1.7 ± 0.3 min^-1 × 10², P < .05). The minimal model analysis of FSIGT data using the method of Bergman et al (Endocr Rev 6:45-86, 1985) showed a reduced second-phase insulin secretion ([Φ₂] E 5.2 ± 1.3 v 13 ± 2.2 μU/mL · min^-2 per mg/dL, P < .05) and glucose disposition index ([SI × Φ₂] E 33.8 ± 10 v 73.9 ± 11 mg^-1 · dL · min^-3 × 10⁴, P < .02). Insulin sensitivity (SI) and glucose-mediated glucose disposal (SG) were unchanged (SI E 6.9 ± 1.0 v 6.0 ± 0.6 min^-1 per μU/mL × 10⁴; SG E 1.8 ± 0.6 v 1.4 ± 0.3 min^-1 × 10²). Reduced glucose tolerance after prolonged extreme physical exercise was accompanied by reduced Φ₂ and not by alterations of SI or SG, despite the marked increase of FFA levels. Elevated norepinephrine levels, reflecting activation of the sympathetic noradrenergic system, was also associated with the reduction in K_g. The reduction in Φ₂ would promote mobilization of FFA, the predominant metabolic substrate in these endurance events.