Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production

Abstract

Calorie restriction (CR) slows aging and is thought to improve insulin sensitivity in laboratory animals. In contrast, decreased insulin signaling and/or mild insulin resistance paradoxically extends maximal lifespan in various genetic animal models of longevity. Nothing is known regarding the long-term effects of CR on glucose tolerance and insulin action in lean healthy humans. In this study we evaluated body composition, glucose, and insulin responses to an oral glucose tolerance test and serum adipokines levels in 28 volunteers, who had been eating a CR diet for an average of 6.9 +/- 5.5 years, (mean age 53.0 +/- 11 years), in 28 age-, sex-, and body fat-matched endurance runners (EX), and 28 age- and sex-matched sedentary controls eating Western diets (WD). We found that the CR and EX volunteers were significantly leaner than the WD volunteers. Insulin sensitivity, determined according to the HOMA-IR and the Matsuda and DeFronzo insulin sensitivity indexes, was significantly higher in the CR and EX groups than in the WD group (P = 0.001). Nonetheless, despite high serum adiponectin and low inflammation, approximately 40% of CR individuals exhibited an exaggerated hyperglycemic response to a glucose load. This impaired glucose tolerance is associated with lower circulating levels of IGF-1, total testosterone, and triiodothyronine, which are typical adaptations to life-extending CR in rodents.

Figures

Fig. 1

Long-term effects of CR and EX on glucose tolerance and insulin action. Mean (±SE) plasma glucose, insulin, and C-peptide concentrations before and after an oral glucose tolerance test for the calorie-restricted (CR) group (black circle), the exercise (EX) group (open circle), and the Western diet (WD) group (black triangle). Baseline values were significantly different between groups for glucose, insulin, and C-peptide (ANOVA). *P ≤ 0.05, significantly different from WD group (Tukey’s tests). **P ≤ 0.05, significantly different from EX group (Tukey’s tests). †P ≤ 0.05, significantly different from CR group (Tukey’s tests)

Fig. 2

Glucose tolerance and insulin action in glucose-intolerant and glucose-tolerant CR individuals. Mean (±SE) plasma glucose, insulin, and C-peptide concentrations before and after an oral glucose tolerance test for the calorie restricted normal glucose tolerance (CR-NGT) subgroup (black circle) and the calorie restricted impaired glucose tolerance (CR-IGT) subgroup (open circle). *P ≤ 0.05, significantly different from CR-IGT subgroup (Student t test)

Fig. 3

Relationship between glucose AUC and serum IGF-1 concentration (upper panel), serum triiodothyronine concentration (middle panel), and serum total testosterone concentration (lower panel) in the CR group. Pearson correlation was used to assess associations between continuous variables