Systemic Immune Mediators and Lifestyle Changes in the Prevention of Type 2 Diabetes

Results From the Finnish Diabetes Prevention Study

  1. Christian Herder1,
  2. Markku Peltonen2,
  3. Wolfgang Koenig3,
  4. Ilka Kräft1,
  5. Sylvia Müller-Scholze1,
  6. Stephan Martin1,
  7. Timo Lakka4,
  8. Pirjo Ilanne-Parikka5,
  9. Johan G. Eriksson2,
  10. Helena Hämäläinen6,
  11. Sirkka Keinänen-Kiukaanniemi7,
  12. Timo T. Valle2,
  13. Matti Uusitupa8,
  14. Jaana Lindström2,
  15. Hubert Kolb1,
  16. Jaakko Tuomilehto2910 and
  17. for the Finnish Diabetes Prevention Study Group
  1. 1German Diabetes Clinic, German Diabetes Center, Leibniz Center at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
  2. 2Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit, National Public Health Institute, Helsinki, Finland
  3. 3Department Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany
  4. 4Department of Physiology, University of Kuopio, Kuopio, Finland
  5. 5Diabetes Center of the Finnish Diabetes Association and the Research Unit of Tampere University Hospital, Tampere, Finland
  6. 6Research Department, Social Insurance Institution, Turku, Finland
  7. 7Department of Public Health Science and General Practice, University of Oulu, Oulu, Finland
  8. 8Department of Clinical Nutrition, University of Kuopio, Kuopio, Finland
  9. 9Department of Public Health, University of Helsinki, Helsinki, Finland
  10. 10South Ostrobothnia Central Hospital, Seinäjoki, Finland
  1. Address correspondence and reprint requests to Dr. Christian Herder, German Diabetes Clinic, German Diabetes Center, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany. E-mail: christian.herder{at}ddz.uni-duesseldorf.de

Abstract

The Finnish DPS (Diabetes Prevention Study) demonstrated that lifestyle intervention, aimed at increasing physical activity, improving diet, and decreasing body weight, reduced the incidence of type 2 diabetes in individuals with overweight and impaired glucose tolerance by 58%. Here, we studied which immunological markers at baseline predicted subsequent type 2 diabetes and whether there are immunologically defined subsets of subjects who are more or less responsive to the protective effects of lifestyle intervention. We randomly assigned 522 participants to a control group (n = 257) or a lifestyle intervention group (n = 265). Immunological parameters at baseline included high-sensitivity C-reactive protein (CRP), serum amyloid A, interleukin-6, regulated on activation normal T-cell expressed and secreted (RANTES), macrophage migration inhibitory factor (MIF), and soluble intercellular adhesion molecule. In the control group, CRP was the best immunological predictor for progression to overt type 2 diabetes. In the intervention group, progression to type 2 diabetes was significantly higher in subjects with the highest RANTES concentrations and was lower in subjects with the highest MIF levels. Ratios of RANTES to MIF in the upper tertile were highly predictive of incident type 2 diabetes in the intervention group (P = 0.006), whereas the association was less pronounced in the control group (P = 0.088). Thus, systemic concentrations of immune mediators appear to be associated with the progression to type 2 diabetes and the prevention of type 2 diabetes by lifestyle changes.

Footnotes

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

    • Accepted May 15, 2006.
    • Received October 11, 2005.
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