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Horm Metab Res 2005; 37(2): 99-105
DOI: 10.1055/s-2005-861174
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Influence of the PPAR-γ2 Pro12Ala and ACE I/D Polymorphisms on Insulin Sensitivity and Training Effects in Healthy Offspring of Type 2 Diabetic Subjects

T.  Østergård 1 , J.  Ek 2 , Y.  Hamid 2 , B.  Saltin 3 , O.  B.  Pedersen 2 , T.  Hansen 2 , O.  Schmitz 1
  • 1Department of Endocrinology and Diabetes M, Aarhus University Hospital, Aarhus Sygehus, and Department of Clinical Pharmacology, University of Aarhus, Aarhus, Denmark
  • 2Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
  • 3Copenhagen Muscle Research Center, Rigshospitalet, Copenhagen, Denmark
Weitere Informationen

Publikationsverlauf

Received 6 May 2004

Accepted after revision 11 August 2004

Publikationsdatum:
21. März 2005 (online)

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Abstract

Aerobic endurance training improves insulin sensitivity, and is of great importance in the prevention and treatment of type 2 diabetes. The improvement in insulin sensitivity and cardiovascular function through exercise is highly variable among individuals, and is probably partly determined by genetic components. This study evaluated the peroxisome proliferation-activated receptor-γ2 (PPAR-γ2) Pro12Ala polymorphism and the angiotensin converting enzyme (ACE) I/D polymorphism with respect to any potential influence that these highly prevalent polymorphisms may impose on changes in insulin sensitivity and maximal aerobic capacity induced by exercise. Seventy-nine healthy first-degree relatives of type 2 diabetic patients were compared to a control group consisting of 54 subjects without any family history of type 2 diabetes. All subjects had a normal OGTT. The groups were comparable with respect to age (34 ± 7 vs. 33 ± 7 years), gender ((m/f) 43/36 vs. 30/24) and BMI (25.7 ± 2.6 vs. 25.3 ± 2.5 kg/m2); p (all) = NS. Furthermore, a subgroup of 29 offspring and 17 control subjects were engaged in a standardized training program lasting ten weeks. Insulin sensitivity (hyperinsulinemic euglycemic clamp technique) and VO2max (exhaustive exercise test) was assessed before and after the training period. We will demonstrate the allelic frequency of the Ala-allele of the Pro12Ala polymorphism to be lower in offspring to type 2 diabetic patients (13.3 %) compared to control subjects (21.3 %); p < 0.05. In offspring only, the Pro12Ala polymorphism of the PPAR-γ2 gene appeared to enhance weight changes brought about by exercise (Δweight = - 0.3 ± 1.4 kg vs. - 1.8 ± 1.8 kg; p < 0.05; (Pro/Pro vs. Pro/Ala + Ala/Ala) - suggesting possible gene-environment or gene-gene interactions. The ACE I/D polymorphism was not of significant importance in determining the capability of responding to exercise in terms of improvement in insulin sensitivity or maximal aerobic capacity.

Key words

Polymorphism · Type 2 diabetes · Exercise · Insulin resistance

References

  • 1 DeFronzo R A, Ferrannini E. .  Diabetes Care. 1991;  14 173-194
    CrossrefPubMedSuche in Google Scholar
  • 2 Tuomilehto J, Lindstrom J, Eriksson J G, Valle T T, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M. .  N Engl J Med. 2001;  344 1343-1350
    CrossrefPubMedSuche in Google Scholar
  • 3 Knowler W C, Barrett-Connor E, Fowler S E, Hamman R F, Lachin J M, Walker E A, Nathan D M. .  N Engl J Med. 2002;  346 393-403
    CrossrefPubMedSuche in Google Scholar
  • 4 McIntyre E A, Walker M. .  Clin Endocrinol (Oxf). 2002;  57 303-311
    CrossrefPubMedSuche in Google Scholar
  • 5 Bouchard C, An P, Rice T, Skinner J S, Wilmore J H, Gagnon J, Perusse L, Leon A S, Rao D C. .  J Appl Physiol. 1999;  87 1003-1008
    CrossrefPubMedSuche in Google Scholar
  • 6 Altshuler D, Hirschhorn J N, Klannemark M, Lindgren C M, Vohl M C, Nemesh J, Lane C R, Schaffner S F, Bolk S, Brewer C, Tuomi T, Gaudet D, Hudson T J, Daly M, Groop L, Lander E S. .  Nat Genet. 2000;  26 76-80
    CrossrefPubMedSuche in Google Scholar
  • 7 Kahara T, Takamura T, Hayakawa T, Nagai Y, Yamaguchi H, Katsuki T, Katsuki K, Katsuki M, Kobayashi K. .  Metabolism. 2003;  52 209-212
    CrossrefPubMedSuche in Google Scholar
  • 8 Lindi V I, Uusitupa M I, Lindstrom J, Louheranta A, Eriksson J G, Valle T T, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Tuomilehto J. .  Diabetes. 2002;  51 2581-2586
    CrossrefPubMedSuche in Google Scholar
  • 9 Katsuya T, Horiuchi M, Chen Y D, Koike G, Pratt R E, Dzau V J, Reaven G M. .  Arterioscler Thromb Vasc Biol. 1995;  15 779-782
    PubMedSuche in Google Scholar
  • 10 Huang X H, Rantalaiho V, Wirta O, Pasternack A, Koivula T, Hiltunen T, Nikkari T, Lehtimaki T. .  Hum Genet. 1998;  102 372-378
    PubMedSuche in Google Scholar
  • 11 Thamer C, Koch M, Haap M, Machicao F, Haring H U, Stumvoll M. .  Atherosclerosis. 2002;  160 257-258
    CrossrefPubMedSuche in Google Scholar
  • 12 Rankinen T, Wolfarth B, Simoneau J A, Maier-Lenz D, Rauramaa R, Rivera M A, Boulay M R, Chagnon Y C, Perusse L, Keul J, Bouchard C. .  J Appl Physiol. 2000;  88 1571-1575
    PubMedSuche in Google Scholar
  • 13 Williams A G, Rayson M P, Jubb M, World M, Woods D R, Hayward M, Martin J, Humphries S E, Montgomery H E. .  Nature. 2000;  403 614
    PubMedSuche in Google Scholar
  • 14 Martin B C, Warram J H, Krolewski A S, Bergman R N, Soeldner J S, Kahn C R. .  Lancet. 1992;  340 925-929
    CrossrefPubMedSuche in Google Scholar
  • 15 Eriksson J, Franssila-Kallunki A, Ekstrand A, Saloranta C, Widen E, Schalin C, Groop L. .  N Engl J Med. 1989;  321 337-343
    CrossrefPubMedSuche in Google Scholar
  • 16 Nyholm B, Fisker S, Lund S, Moller N, Schmitz O. .  Eur J Endocrinol. 1997;  136 173-179
    PubMedSuche in Google Scholar
  • 17 Aastrand I. .  Acta Physiologica Scandinavia. 1960;  49 1-92
    PubMedSuche in Google Scholar
  • 18 Ek J, Urhammer S A, Sorensen T I, Andersen T, Auwerx J, Pedersen O. .  Diabetologia. 1999;  42 892-895
    CrossrefPubMedSuche in Google Scholar
  • 19 Saltin B, Grimby G. .  Circulation. 1968;  38 1104-1115
    CrossrefPubMedSuche in Google Scholar
  • 20 Baecke J A, Burema J, Frijters J E. .  Am J Clin Nutr. 1982;  36 936-942
    PubMedSuche in Google Scholar
  • 21 Yen C J, Beamer B A, Negri C, Silver K, Brown K A, Yarnall D P, Burns D K, Roth J, Shuldiner A R. .  Biochem Biophys Res Commun. 1997;  241 270-274
    CrossrefPubMedSuche in Google Scholar
  • 22 Douglas J A, Erdos M R, Watanabe R M, Braun A, Johnston C L, Oeth P, Mohlke K L, Valle T T, Ehnholm C, Buchanan T A, Bergman R N, Collins F S, Boehnke M, Tuomilehto J. .  Diabetes. 2001;  50 886-890
    PubMedSuche in Google Scholar
  • 23 Ek J, Andersen G, Urhammer S A, Hansen L, Carstensen B, Borch-Johnsen K, Drivsholm T, Berglund L, Hansen T, Lithell H, Pedersen O. .  Diabetologia. 2001;  44 1170-1176
    CrossrefPubMedSuche in Google Scholar
  • 24 Jacob S, Stumvoll M, Becker R, Koch M, Nielsen M, Loblein K, Maerker E, Volk A, Renn W, Balletshofer B, Machicao F, Rett K, Haring H U. .  Horm Metab Res. 2000;  32 413-416
    PubMedSuche in Google Scholar
  • 25 Deeb S S, Fajas L, Nemoto M, Pihlajamaki J, Mykkanen L, Kuusisto J, Laakso M, Fujimoto W, Auwerx J. .  Nat Genet. 1998;  20 284-287
    CrossrefPubMedSuche in Google Scholar
  • 26 Stumvoll M, Haring H. .  Diabetes. 2002;  51 2341-2347
    PubMedSuche in Google Scholar
  • 27 Hara K, Okada T, Tobe K, Yasuda K, Mori Y, Kadowaki H, Hagura R, Akanuma Y, Kimura S, Ito C, Kadowaki T. .  Biochem Biophys Res Commun. 2000;  271 212-216
    CrossrefPubMedSuche in Google Scholar
  • 28 Stumvoll M, Wahl H G, Loblein K, Becker R, Machicao F, Jacob S, Haring H. .  Diabetes. 2001;  50 876-881
    PubMedSuche in Google Scholar
  • 29 Koch M, Rett K, Maerker E, Volk A, Haist K, Deninger M, Renn W, Haring H U. .  Diabetologia. 1999;  42 758-762
    CrossrefPubMedSuche in Google Scholar
  • 30 Luan J, Browne P O, Harding A H, Halsall D J, O'Rahilly S, Chatterjee V K, Wareham N J. .  Diabetes. 2001;  50 686-689
    PubMedSuche in Google Scholar
  • 31 Nicklas B J, van Rossum E F, Berman D M, Ryan A S, Dennis K E, Shuldiner A R. .  Diabetes. 2001;  50 2172-2176
    CrossrefPubMedSuche in Google Scholar
  • 32 Pihlajamaki J, Vanhala M, Vanhala P, Laakso M. .  Obes Res. 2004;  12 187-190
    PubMedSuche in Google Scholar
  • 33 Montgomery H, Clarkson P, Barnard M, Bell J, Brynes A, Dollery C, Hajnal J, Hemingway H, Mercer D, Jarman P, Marshall R, Prasad K, Rayson M, Saeed N, Talmud P, Thomas L, Jubb M, World M, Humphries S. .  Lancet. 1999;  353 541-545
    CrossrefPubMedSuche in Google Scholar
  • 34 Strazzullo P, Iacone R, Iacoviello L, Russo O, Barba G, Russo P, D'Orazio A, Barbato A, Cappuccio F P, Farinaro E, Siani A. .  Ann Intern Med. 2003;  138 17-23
    PubMedSuche in Google Scholar
  • 35 Wang J G, He X, Wang G L, Li Y, Zhou H F, Zhang W Z, Zhan Y M, Zhu D L. .  J Hypertens. 2004;  22 487-491
    PubMedSuche in Google Scholar
  • 36 Panahloo A, Andres C, Mohamed-Ali V, Gould M M, Talmud P, Humphries S E, Yudkin J S. .  Circulation. 1995;  92 3390-3393
    PubMedSuche in Google Scholar
  • 37 Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. .  J Clin Invest. 1990;  86 1343-1346
    CrossrefPubMedSuche in Google Scholar
  • 38 Pollare T, Lithell H, Berne C. .  N Engl J Med. 1989;  321 868-873
    CrossrefPubMedSuche in Google Scholar
  • 39 Heise T, Heinemann L, Kristahn K, Berger M, Sawicki P T. .  Horm Metab Res. 1999;  31 418-423
    PubMedSuche in Google Scholar
  • 40 Rankinen T, Perusse L, Gagnon J, Chagnon Y C, Leon A S, Skinner J S, Wilmore J H, Rao D C, Bouchard C. .  J Appl Physiol. 2000;  88 1029-1035
    PubMedSuche in Google Scholar
  • 41 Sonna L A, Sharp M A, Knapik J J, Cullivan M, Angel K C, Patton J F, Lilly C M. .  J Appl Physiol. 2001;  91 1355-1363
    CrossrefPubMedSuche in Google Scholar
  • 42 Montgomery H E, Marshall R, Hemingway H, Myerson S, Clarkson P, Dollery C, Hayward M, Holliman D E, Jubb M, World M, Thomas E L, Brynes A E, Saeed N, Barnard M, Bell J D, Prasad K, Rayson M, Talmud P J, Humphries S E. .  Nature. 1998;  393 221-222
    CrossrefPubMedSuche in Google Scholar

T. Østergård, M. D.

Department of Medicine M (Endocrinology & Diabetes) Aarhus University Hospital, Aarhus Sygehus

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