TY - JOUR
T1 - Improvements in glucose homeostasis in response to regular exercise are influenced by the PPARG Pro12Ala variant
T2 - Results from the HERITAGE family study
AU - Pérusse, L.
AU - Ruchat, S. M.
AU - Rankinen, T.
AU - Weisnagel, S. J.
AU - Rice, T.
AU - Rao, D. C.
AU - Bergman, R. N.
AU - Bouchard, C.
N1 - Funding Information:
Acknowledgements The HERITAGE Family Study has been supported over the years by the National Heart, Lung, and Blood Institute (Grants HL-45670, HL-47317, HL-47323, HL-47327 and HL-47321). The study continues to be supported by HL-45670. Thanks are expressed to A. S. Leon, J. S. Skinner and J. H. Wilmore for their contributions to the HERITAGE Family Study. C. Bouchard is partially supported by the George A. Bray Chair in Nutrition. S.-M. Ruchat is supported by a scholarship from the Canadian Diabetes Association.
PY - 2010/4
Y1 - 2010/4
N2 - Aims/hypothesis: Exercise training improves glucose homeostasis, but large inter-individual differences are reported, suggesting a role of genetic factors. We investigated whether variants either confirmed or newly identified as diabetes susceptibility variants through genome-wide association studies (GWAS) modulate changes in phenotypes derived from an IVGTT in response to an endurance training programme. Methods: We analysed eight polymorphisms in seven type 2 diabetes genes (CDKAL1 rs7756992; CDKN2A and CDKN2B rs10811661 and rs564398; HHEX rs7923837; IGF2BP2 rs4402960; KCNJ11 rs5215; PPARG rs1801282; and TCF7L2 rs7903146) in a maximum of 481 sedentary, non-diabetic white individuals, who participated in a 20-week endurance training programme. Associations were tested between the variants and changes in IVGTT-derived phenotypes. Results: The only evidence of association with training response was found with PPARG rs1801282 (Pro12Ala). We observed that Ala carriers experienced greater increase in overall glucose tolerance (Δglucose disappearance index Ala/Ala 0.22±0.22, Pro/Ala 0.14±0.06, Pro/Pro 0.004±0.03; p=0.0008), glucose effectiveness (Ala/Ala 0.28±0.41, Pro/Ala 0.44±0.14, Pro/Pro 0.09±0.06; p=0.004), acute insulin response to glucose (Ala/Ala 64.21±37.73, Pro/Ala -11.92±40.30, Pro/Pro -46.30±14.70; p=0.03) and disposition index (Ala/Ala 551.8±448.5, Pro/Ala 534.6±218.3, Pro/Pro -7.44±88.18; p=0.003). Conclusions/interpretation: Compared with Pro/Pro individuals, PPARG Ala carriers experienced greater improvements in glucose and insulin metabolism in response to regular endurance training. However, we did not find evidence of association between type 2 diabetes susceptibility variants recently identified through GWAS and glucose homeostasis response to exercise. Our results extend those of previous studies showing that Ala carriers appear to be more responsive to beneficial health effects of lifestyle interventions.
AB - Aims/hypothesis: Exercise training improves glucose homeostasis, but large inter-individual differences are reported, suggesting a role of genetic factors. We investigated whether variants either confirmed or newly identified as diabetes susceptibility variants through genome-wide association studies (GWAS) modulate changes in phenotypes derived from an IVGTT in response to an endurance training programme. Methods: We analysed eight polymorphisms in seven type 2 diabetes genes (CDKAL1 rs7756992; CDKN2A and CDKN2B rs10811661 and rs564398; HHEX rs7923837; IGF2BP2 rs4402960; KCNJ11 rs5215; PPARG rs1801282; and TCF7L2 rs7903146) in a maximum of 481 sedentary, non-diabetic white individuals, who participated in a 20-week endurance training programme. Associations were tested between the variants and changes in IVGTT-derived phenotypes. Results: The only evidence of association with training response was found with PPARG rs1801282 (Pro12Ala). We observed that Ala carriers experienced greater increase in overall glucose tolerance (Δglucose disappearance index Ala/Ala 0.22±0.22, Pro/Ala 0.14±0.06, Pro/Pro 0.004±0.03; p=0.0008), glucose effectiveness (Ala/Ala 0.28±0.41, Pro/Ala 0.44±0.14, Pro/Pro 0.09±0.06; p=0.004), acute insulin response to glucose (Ala/Ala 64.21±37.73, Pro/Ala -11.92±40.30, Pro/Pro -46.30±14.70; p=0.03) and disposition index (Ala/Ala 551.8±448.5, Pro/Ala 534.6±218.3, Pro/Pro -7.44±88.18; p=0.003). Conclusions/interpretation: Compared with Pro/Pro individuals, PPARG Ala carriers experienced greater improvements in glucose and insulin metabolism in response to regular endurance training. However, we did not find evidence of association between type 2 diabetes susceptibility variants recently identified through GWAS and glucose homeostasis response to exercise. Our results extend those of previous studies showing that Ala carriers appear to be more responsive to beneficial health effects of lifestyle interventions.
KW - Diabetes susceptibility genes
KW - IVGTT-derived phenotypes
KW - Polymorphisms
KW - Response to exercise
UR - http://www.scopus.com/inward/record.url?scp=77949268950&partnerID=8YFLogxK
U2 - 10.1007/s00125-009-1630-2
DO - 10.1007/s00125-009-1630-2
M3 - Article
C2 - 20043145
AN - SCOPUS:77949268950
SN - 0012-186X
VL - 53
SP - 679
EP - 689
JO - Diabetologia
JF - Diabetologia
IS - 4
ER -