, Volume 32, Issue 1, pp 97–108 | Cite as

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

  • Luigi FontanaEmail author
  • Samuel Klein
  • John O. Holloszy


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, ∼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.


Calorie restriction Endurance exercise Glucose tolerance Insulin action Adipokines Glycation 



We are grateful to the study participants for their cooperation and to the staff of the Applied Physiology Laboratory and nurses of the General Clinical Research Center at WUMS for their skilled assistance. The study design was developed by LF and JOH; data collection was performed and supervised by LF; data analyses and interpretation were performed by LF, SK, and JOH; writing was performed by LF, SK, and JOH. LF had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All the authors declare that they participated in the study as mentioned above and that they reviewed and approved the manuscript in its final version.

Financial disclosures

The author had no conflicts of interest.


This study was supported by Grant Number UL1 RR024992 from the National Center for Research Resources (a component of the National Institutes of Health and NIH Roadmap for Medical Research), by Istituto Superiore di Sanità/National Institutes of Health Collaboration Program Grant, a grant from the Longer Life Foundation (an RGA/Washington University Partnership), and a donation from the Scott and Annie Appleby Charitable Trust.

Role of the sponsor

The funding agencies had no role in the analysis or interpretation of the data or in the decision to submit the report for publication.


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Copyright information

© American Aging Association, Media, PA, USA 2009

Authors and Affiliations

  • Luigi Fontana
    • 1
    • 2
    Email author
  • Samuel Klein
    • 1
  • John O. Holloszy
    • 1
  1. 1.Division of Geriatrics and Nutritional Science and Center for Human NutritionWashington University School of MedicineSt. LouisUSA
  2. 2.Division of Nutrition and AgingIstituto Superiore di SanitàRomeItaly

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