title: Systemic immune mediators and lifestyle changes in the prevention of type 2 diabetes: results from the Finnish Diabetes Prevention Study.
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.
authors.affiliation: German Diabetes Clinic, German Diabetes Center, Leibniz Center at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany. christian.herder@ddz.uni-duesseldorf.de
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.forename: Markku
authors.initials: M
authors.lastname: Peltonen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Ilka
authors.initials: I
authors.lastname: Kräft
authors.forename: Sylvia
authors.initials: S
authors.lastname: Müller-Scholze
authors.forename: Stephan
authors.initials: S
authors.lastname: Martin
authors.forename: Timo
authors.initials: T
authors.lastname: Lakka
authors.forename: Pirjo
authors.initials: P
authors.lastname: Ilanne-Parikka
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.forename: Helena
authors.initials: H
authors.lastname: Hämäläinen
authors.forename: Sirkka
authors.initials: S
authors.lastname: Keinänen-Kiukaanniemi
authors.forename: Timo T
authors.initials: TT
authors.lastname: Valle
authors.forename: Matti
authors.initials: M
authors.lastname: Uusitupa
authors.forename: Jaana
authors.initials: J
authors.lastname: Lindström
authors.forename: Hubert
authors.initials: H
authors.lastname: Kolb
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
mesh_terms: D000886:Anthropometry; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000517:prevention & control*; D004032:Diet; D015444:Exercise; D005260:Female; D005387:Finland; D005951:Glucose Tolerance Test; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008019:Life Style; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000276:immunology; D008875:Middle Aged; D000685:Serum Amyloid A Protein / Q000032:analysis; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018946:Chemokine CCL5; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein