title: 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.
authors.affiliation: Washington University School of Medicine, St. Louis, MO 63110, USA. lfontana@dom.wustl.edu
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
authors.forename: John O
authors.initials: JO
authors.lastname: Holloszy
mesh_terms: D054392:Adipokines / Q000097:blood*; D000704:Analysis of Variance; D019540:Area Under Curve; D001823:Body Composition; D031204:Caloric Restriction; D016022:Case-Control Studies; D015444:Exercise / Q000502:physiology*; D005260:Female; D005951:Glucose Tolerance Test; D006728:Hormones / Q000097:blood; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010807:Physical Endurance / Q000502:physiology*; D012420:Running / Q000502:physiology; D015398:Signal Transduction; D013739:Testosterone / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D054392:Adipokines; D006728:Hormones; D014284:Triiodothyronine; D013739:Testosterone; D007334:Insulin-Like Growth Factor I