Leptin and Leptin Receptor Gene Polymorphisms and Changes in Glucose Homeostasis in Response to Regular Exercise in Nondiabetic Individuals
The HERITAGE Family Study
- Timo A. Lakka12,
- Tuomo Rankinen1,
- S. John Weisnagel3,
- Yvon C. Chagnon4,
- Hanna-Maaria Lakka1,
- Olavi Ukkola5,
- Normand Boulé3,
- Treva Rice6,
- Arthur S. Leon7,
- James S. Skinner8,
- Jack H. Wilmore9,
- D.C. Rao61011,
- Richard Bergman12 and
- Claude Bouchard1
- 1Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana
- 2Kuopio Research Institute of Exercise Medicine, University of Kuopio, Kuopio, Finland
- 3Department of Social & Preventive Medicine, Laval University, Ste-Foy, Québec, Canada
- 4Laval University, Ste-Foy, Québec, Canada
- 5Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
- 6Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri
- 7School of Kinesiology and Leisure Studies, University of Minnesota, Minneapolis, Minnesota
- 8Department of Kinesiology, Indiana University, Bloomington, Indiana
- 9Department of Health and Kinesiology, Texas A & M University, College Station, Texas
- 10Department of Genetics, Washington University School of Medicine, St. Louis, Missouri
- 11Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
- 12Keck School of Medicine, University of Southern California, Los Angeles, California
- Address correspondence and reprint requests to Timo A. Lakka, Human Genomics Laboratory, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808-4124. E-mail: lakkat{at}pbrc.edu
Abstract
We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. Similar interaction was observed in blacks (P = 0.046). Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals.
- AIRg, acute insulin response to intravenous glucose
- FSIVGT, frequently sampled intravenous glucose tolerance test
Footnotes
-
C.B. has served on advisory panels for the U.S. Department of Agriculture, the National Institutes of Health, the Institutes for Pharmaceutical Discovery, Mars, Sanofi-synthelabo, The Cooper Institute for Aerobic Research, and Weight Watchers International; has received consulting fees from the Almond Board of California and Bristol Myers Squibb; and has received grant support from Bristol Myers Squibb.
-
- Accepted March 1, 2004.
- Received November 13, 2003.
- DIABETES
