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. Lakka, Tuomo Rankinen, S. John Weisnagel, Yvon C. Chagnon, Hanna Maaria Lakka, Olavi Ukkola, Normand Boulé, Treva Rice, Arthur S. Leon, James S. Skinner, Jack H. Wilmore, D. C. Rao, Richard Bergman, Claude Bouchard

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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.

Original languageEnglish
Pages (from-to)1603-1608
Number of pages6
JournalDiabetes
Volume53
Issue number6
DOIs
StatePublished - Jun 1 2004

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    Lakka, T. A., Rankinen, T., Weisnagel, S. J., Chagnon, Y. C., Lakka, H. M., Ukkola, O., Boulé, N., Rice, T., Leon, A. S., Skinner, J. S., Wilmore, J. H., Rao, D. C., Bergman, R., & Bouchard, C. (2004). Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals: The HERITAGE Family Study. Diabetes, 53(6), 1603-1608. https://doi.org/10.2337/diabetes.53.6.1603