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Published online March 10, 2007
Diabetes Care 30:1618-1620, 2007
DOI: 10.2337/dc06-2467
© 2007 by the American Diabetes Association
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Cardiovascular and Metabolic Risk
Brief Report

Leisure-Time Physical Activity Is Associated With the Metabolic Syndrome in Type 1 Diabetes

Effect of the PPAR{gamma} Pro12Ala polymorphism: the FinnDiane Study

Johan Wadén, MD1,2, Lena M. Thorn, MD1,2, Carol Forsblom, MD, DMSC1,2, Timo Lakka, MD, DMSC3,4, Markku Saraheimo, MD1,2, Milla Rosengård-Bärlund, MD1,2, Outi Heikkilä, MD1,2, Maija Wessman, PHD1,2,5, Joni A. Turunen, MD1,2, Maija Parkkonen, BSC1,2, Heikki Tikkanen, MD, DMSC1,6, Per-Henrik Groop, MD, DMSC1,2 on behalf of the FinnDiane Study Group

1 Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
2 Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
3 Department of Physiology, Institute of Biomedicine, University of Kuopio, Kuopio, Finland
4 Kuopio Research Institute of Exercise Medicine, Kuopio, Finland
5 Finnish Genome Center, University of Helsinki, Finland
6 Unit for Sports and Exercise Medicine, Institute of Clinical Medicine, University of Helsinki, Finland

Address correspondence and reprint requests to Per-Henrik Groop, Biomedicum Helsinki, POB 63, 00014 University of Helsinki, Finland. E-mail: per-henrik.groop{at}helsinki.fi

Abbreviations: FinnDiane, Finnish Diabetic Nephropathy • LTPA, leisure-time physical activity


   INTRODUCTION
TOP
 INTRODUCTION
RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 
The metabolic syndrome varies in prevalence among different populations. A common feature, however, is a steep increase in prevalence along with a decrease in glucose tolerance (1–2).

We have shown that 39% of adult type 1 diabetic patients have the metabolic syndrome (3), and similar data were recently reported from Italy (4). However, whether the metabolic syndrome observed in type 1 diabetes is the same as in nondiabetic and type 2 diabetic patients is unclear.

Both lifestyle (5–8) and hereditary factors (9) seem to be involved in the development of the metabolic syndrome in nondiabetic and type 2 diabetic subjects. The PPAR{gamma} (peroxisome proliferator-activated receptor {gamma}) Pro12Ala polymorphism has been associated with type 2 diabetes, the Ala allele being associated with a lower risk (10), and with the metabolic syndrome in some (11–12) but not all (13) studies. However, whether lifestyle or genetic factors also play a role in the development and treatment of the metabolic syndrome in patients with type 1 diabetes is unknown.

Therefore, to further study the metabolic syndrome in type 1 diabetes, we investigated whether physical activity and/or the PPAR{gamma} Pro12Ala polymorphism are associated with metabolic syndrome in patients with type 1 diabetes in the Finnish Diabetic Nephropathy (FinnDiane) Study.


   RESEARCH DESIGN AND METHODS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
RESULTS--
 CONCLUSIONS--
 References
 
Using a cross-sectional study design, 1,028 type 1 diabetic patients from the FinnDiane Study (3,14) with data on leisure-time physical activity (LTPA) and metabolic syndrome were studied. Patients with end-stage renal disease and/or cardiovascular events were excluded.

Metabolic syndrome was defined according to the NCEP/ATP III (National Cholesterol Education Program/Adult Treatment Panel III) criteria (15). LTPA (as MET h/week) was assessed by a validated 12-month questionnaire (16), and patients were grouped as sedentary, moderately active, or active as previously described (14). The PPAR{gamma} Pro12Ala (rs1801282) polymorphism was studied from 840 of the 1,028 patients using an ABI Prism 7900 Sequence Detection System (Applied Biosystems, Foster City, CA).


   RESULTS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
CONCLUSIONS--
 References
 
The mean ± SD age was 36.4 ± 11.5 years, duration of diabetes 21.3 ± 11.7 years, A1C 8.4 ± 1.4%, BMI 25.0 ± 3.3 kg/m2, and 47% of patients were men. Median (interquartile range) LTPA was 19.7 (10.0–34.1) MET h/week. The prevalence of metabolic syndrome was 29.5% (ratio of men to women 27.8:31.0%, P = 0.269); 31.8% had the Ala-allele for PPAR{gamma} Pro12Ala (2.6% were homozygous). According to genotype, there were no differences in BMI, waist-to-hip ratio, lipid profile or, A1C (data not shown).

The prevalence of metabolic syndrome did not differ by genotype (Pro12Pro 30.4%, Pro12Ala 30.6%, Ala12Ala 36.4%; P = 0.836). LTPA in the presence versus absence of metabolic syndrome was 17.0 (8.6–31.6) vs. 20.8 (10.8–34.7) MET h/week (age-adjusted P = 0.038). Table 1 shows the prevalences of the metabolic syndrome and its individual components according to LTPA and PPAR{gamma} genotype.


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  		Table 1— Proportion of type 1 diabetic patients with the metabolic syndrome and its individual components* according to level of LTPA and genotype for PPAR{gamma} Pro12Ala

 
Among patients reporting LTPA of low, moderate, or high intensity, 39.0, 28.3, and 23.2% (age-adjusted P = 0.008) had metabolic syndrome, respectively. Regarding frequency of LTPA, corresponding prevalences for <1, 1–2, or ≥3 sessions/week were 33.0, 29.9, and 27.7% (age-adjusted P = 0.325), respectively.

In a multiple logistic regression model, LTPA as a log-transformed continuous variable (odds ratio [OR] 0.73 [95% CI 0.58–0.92]) and laser-treated retinopathy (1.97 [1.19–3.27]) were independently associated with the metabolic syndrome. The model also included PPAR{gamma} Pro12Pro genotype (0.99 [0.62–1.58]), weekly doses (12 g/dose) of alcohol (1.26 [0.98–1.60]), male sex (0.98 [0.62–1.56]), age (1.01 [0.99–1.03]), low social class (1.09 [0.69–1.72]), smoking (0.76 [0.45–1.30]), and diabetic nephropathy (1.84 [0.92–3.68]).


   CONCLUSIONS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
References
 
Low LTPA was associated with a higher prevalence of the metabolic syndrome, supporting our previous findings on LTPA and insulin sensitivity in type 1 diabetes (14). Due to the cross-sectional study design, LTPA could have been reduced by exercise-limiting factors associated with the metabolic syndrome. However, the likelihood of complication-derived physical activity bias was reduced by controlling for diabetes complications.

The PPAR{gamma} Pro12Ala polymorphism was not associated with the metabolic syndrome. Patients with the Ala allele, however, had a 2.4-fold higher prevalence of the metabolic syndrome when sedentary patients were compared with those who were physically active, while in patients with the Pro12Pro genotype, LTPA did not affect the prevalence of the metabolic syndrome. Of individual criteria, waist circumference seemed important for this genotype-dependent association, favoring a pivotal role of insulin sensitivity, the key factor in the metabolic syndrome (17).

Interestingly, the Ala allele has been associated with greater exercise-induced improvement of insulin sensitivity measures (18–19) in healthy individuals and reduction in fasting plasma glucose in type 2 diabetic patients (20). In the Finnish Diabetes Prevention Study, a paradoxical diabetogenic effect of the Ala allele in subjects with impaired glucose tolerance was eliminated by lifestyle intervention (21).

Based on our study and the findings of the Finnish Diabetes Prevention Study, the Ala allele might be viewed as not exclusively beneficial for insulin sensitivity and glucose homeostasis because the Ala allele, when combined with low physical activity, may on the contrary be detrimental. In our study, sedentary Ala carriers more frequently had metabolic syndrome than sedentary patients with Pro12Pro genotype. Thus, PPAR{gamma} Pro12Ala may be a true exercise-response gene variant working in both directions, promoting insulin sensitivity in those who are physically active while impeding sensitivity in sedentary subjects.


   Acknowledgments
 
This study was supported by the Folkhälsan Research Foundation, Samfundet Folkhälsan, Wilhelm och Else Stockmann Foundation, Sigrid Juselius Foundation, Waldemar von Frenckell Foundation, Liv och Hälsa Foundation, the Academy of Finland (no. 214335), and the European Commission (QLG2-CT-2001-01669). The assistance of Anna Sandelin, Sinikka Lindh, and Susanne Ström is gratefully acknowledged. Finally, we acknowledge physicians and nurses at each study center, presented in an online appendix (available at http://dx.doi.org/10.2337/dc06-2467).


   Footnotes
 
Published ahead of print at http://care.diabetesjournals.org on 10 March 2007. DOI: 10.2337/dc06-2467.

Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc06-2467.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

Received for publication December 4, 2006. Accepted for publication February 28, 2007.


   References
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 

  1. Isomaa B, Almgren P, Tuomi T, Forsén B, Lahti K, Nissen M, Taskinen MR, Groop L: Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24:683–689, 2001[Abstract/Free Full Text]
  2. Ilanne-Parikka P, Eriksson JG, Lindström J, Hämälainen H, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Mannelin M, Rastas M, Salminen V, Aunola S, Sundvall J, Valle T, Lahtela J, Uusitupa M, Tuomilehto J, the Finnish Diabetes Prevention Study Group: Prevalence of the metabolic syndrome and its components: findings from a Finnish general population sample and the Diabetes Prevention Study cohort. Diabetes Care 27:2135–2140, 2004[Abstract/Free Full Text]
  3. Thorn LM, Forsblom C, Fagerudd J, Thomas MC, Pettersson-Fernholm K, Saraheimo M, Wadén J, Rönnback M, Rosengård-Bärlund M, Björkesten CG, Taskinen MR, Groop PH, the FinnDiane Study Group: Metabolic syndrome in type 1 diabetes: association with diabetic nephropathy and glycemic control (the FinnDiane study). Diabetes Care 28:2019–2024, 2005[Abstract/Free Full Text]
  4. The Metascreen Writing Committee: The metabolic syndrome is a risk indicator of microvascular and macrovascular complications in diabetes: results from Metascreen, a multicenter diabetes clinic–based survey. Diabetes Care 29:2701–2707, 2006[Abstract/Free Full Text]
  5. Eriksson J, Taimela S, Koivisto VA: Exercise and the metabolic syndrome. Diabetologia 40:125–135, 1997[Medline]
  6. Lakka TA, Laaksonen DE, Lakka HM, Männikkö N, Niskanen LK, Rauramaa R, Salonen JT: Sedentary lifestyle, poor cardiorespiratory fitness, and the metabolic syndrome. Med Sci Sports Exerc 35:1279–1286, 2003
  7. Aude YW, Mego P, Mehta JL: Metabolic syndrome: dietary interventions. Curr Opin Cardiol 19:473–479, 2004[Medline]
  8. Orchard TJ, Temprosa M, Goldberg R, Haffner S, Ratner R, Marcovina S, Fowler S, the Diabetes Prevention Program Research Group: The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med 142:611–619, 2005[Abstract/Free Full Text]
  9. Tang W, Hong Y, Province MA, Rich SS, Hopkins PN, Arnett DK, Pankow JS, Miller MB, Eckfeldt JH: Familial clustering for features of the metabolic syndrome. Diabetes Care 29:631–636, 2006[Abstract/Free Full Text]
  10. Altshuler D, Hirschhorn JN, Klannemark M, Lindgren CM, Vohl MC, Nemesh J, Lane CR, Schaffner SF, Bolk S, Brewer C, Tuomi T, Gaudet D, Hudson TJ, Daly M, Groop L, Lander ES: The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 26:76–80, 2000[Medline]
  11. Meirhaeghe A, Cottel D, Amouyel P, Dallongeville J: Association between peroxisome proliferator-activated receptor {gamma} haplotypes and the metabolic syndrome in French men and women. Diabetes 54:3043–3048, 2005[Abstract/Free Full Text]
  12. Frederiksen L, Brodbaek K, Fenger M, Jorgensen T, Borch-Johnsen K, Madsbad S, Urhammer SA: Studies of the Pro12Ala polymorphism of the PPAR-gamma gene in the Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome. J Clin Endocrinol Metab 87:3989–3992, 2002[Abstract/Free Full Text]
  13. Rhee EJ, Oh KW, Lee WY, Kim SY, Oh ES, Baek KH, Kang MI, Kim SW: Effects of two common polymorphisms of peroxisome proliferator-activated receptor-gamma gene on metabolic syndrome. Archives of Medical Research 37:86–94, 2006[Medline]
  14. Wadén J, Tikkanen H, Forsblom C, Fagerudd J, Pettersson-Fernholm K, Lakka T, Riska M, Groop PH, the FinnDiane Study G: Leisure time physical activity is associated with poor glycemic control in type 1 diabetic women: the FinnDiane study. Diabetes Care 28:777–782, 2005[Abstract/Free Full Text]
  15. Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 285:2486–2497, 2001[Free Full Text]
  16. Salonen JT, Lakka TA: Assessment of physical activity in population studies: validity and consistency of the methods in the Kuopio Ishemic Heart Disease Risk Factor Study. Scand J Sports Sci 9:89–95, 1987
  17. DeFronzo RA, Ferrannini E: Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14:173–194, 1991[Abstract]
  18. Kahara T, Takamura T, Hayakawa T, Nagai Y, Yamaguchi H, Katsuki T, Katsuki K, Katsuki M, Kobayashi K: PPARgamma gene polymorphism is associated with exercise-mediated changes of insulin resistance in healthy men. Metabolism 52:209–212, 2003[Medline]
  19. Weiss EP, Kulaputana O, Ghiu IA, Brandauer J, Wohn CR, Phares DA, Shuldiner AR, Hagberg JM: Endurance training-induced changes in the insulin response to oral glucose are associated with the peroxisome proliferator-activated receptor-gamma2 Pro12Ala genotype in men but not in women. Metabolism 54:97–102, 2005[Medline]
  20. Adamo KB, Sigal RJ, Williams K, Kenny G, Prud'homme D, Tesson F: Influence of Pro12Ala peroxisome proliferator-activated receptor gamma2 polymorphism on glucose response to exercise training in type 2 diabetes. Diabetologia 48:1503–1509, 2005[Medline]
  21. Lindi VI, Uusitupa MI, Lindström J, Louheranta A, Eriksson JG, Valle TT, Hämälainen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Tuomilehto J, the Finnish Diabetes Prevention Study: Association of the Pro12Ala polymorphism in the PPAR-{gamma}2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study. Diabetes 51:2581–2586, 2002[Abstract/Free Full Text]

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