OBJECTIVES: To examine whether interleukin-1 receptor antagonist (IL-1Ra) is a predictor for clinically incident diabetes in subjects with metabolic syndrome (MetS) and whether its predictive power is independent of C-reactive protein (CRP), an established marker of inflammation. We further examined whether genetic variants at the interleukin-1 (IL-1) locus would predict clinically incident diabetes. DESIGN: Two observational prospective cohort studies. SETTING: Two separate cohorts, Health 2000 and FINRISK 1997, followed up for an average of 7.1 and 10.8 years, respectively. SUBJECTS: Random population samples consisting of 5511 subjects aged 30-74 years in Health 2000 and 7374 subjects aged 25-74 years in FINRISK 1997. RESULTS: During follow-up, 141 cases of clinically incident diabetes were observed amongst subjects with MetS at baseline in Health 2000 and 248 cases in FINRISK 97. After adjustment for multiple traditional risk factors of diabetes, including age and body mass index, IL-1Ra was a significant (P < 0.01) predictor of incident diabetes amongst men in both cohorts and amongst women in FINRISK 1997. Further adjustment for CRP reduced the hazard ratios only slightly. Genetic analyses produced nominally significant associations for three single-nucleotide polymorphisms: rs3213448 in IL-1 receptor antagonist (IL1RN), rs1143634 in IL-1 beta (IL1B) and rs1800587 in IL-1 alpha (IL1A). The two latter variants had an interaction with gender (P = 0.023 and 0.002, respectively) suggesting the presence of gender-specific associations with the risk of clinically incident diabetes. CONCLUSIONS: IL-1Ra predicted the progression of MetS to clinically incident diabetes independently of CRP and other risk factors. Genetic variation in the IL-1 locus may have gender-specific associations with the risk of type 2 diabetes.
OBJECTIVES: To examine whether interleukin-1 receptor antagonist (IL-1Ra) is a predictor for clinically incident diabetes in subjects with metabolic syndrome (MetS) and whether its predictive power is independent of C-reactive protein (CRP), an established marker of inflammation. We further examined whether genetic variants at the interleukin-1 (IL-1) locus would predict clinically incident diabetes. DESIGN: Two observational prospective cohort studies. SETTING: Two separate cohorts, Health 2000 and FINRISK 1997, followed up for an average of 7.1 and 10.8 years, respectively. SUBJECTS: Random population samples consisting of 5511 subjects aged 30-74 years in Health 2000 and 7374 subjects aged 25-74 years in FINRISK 1997. RESULTS: During follow-up, 141 cases of clinically incident diabetes were observed amongst subjects with MetS at baseline in Health 2000 and 248 cases in FINRISK 97. After adjustment for multiple traditional risk factors of diabetes, including age and body mass index, IL-1Ra was a significant (P < 0.01) predictor of incident diabetes amongst men in both cohorts and amongst women in FINRISK 1997. Further adjustment for CRP reduced the hazard ratios only slightly. Genetic analyses produced nominally significant associations for three single-nucleotide polymorphisms: rs3213448 in IL-1 receptor antagonist (IL1RN), rs1143634 in IL-1 beta (IL1B) and rs1800587 in IL-1 alpha (IL1A). The two latter variants had an interaction with gender (P = 0.023 and 0.002, respectively) suggesting the presence of gender-specific associations with the risk of clinically incident diabetes. CONCLUSIONS:IL-1Ra predicted the progression of MetS to clinically incident diabetes independently of CRP and other risk factors. Genetic variation in the IL-1 locus may have gender-specific associations with the risk of type 2 diabetes.
Authors: M Uusitupa; K Hermansen; M J Savolainen; U Schwab; M Kolehmainen; L Brader; L S Mortensen; L Cloetens; A Johansson-Persson; G Onning; M Landin-Olsson; K-H Herzig; J Hukkanen; F Rosqvist; D Iggman; J Paananen; K J Pulkki; M Siloaho; L Dragsted; T Barri; K Overvad; K E Bach Knudsen; M S Hedemann; P Arner; I Dahlman; G I A Borge; P Baardseth; S M Ulven; I Gunnarsdottir; S Jónsdóttir; I Thorsdottir; M Orešič; K S Poutanen; U Risérus; B Akesson Journal: J Intern Med Date: 2013-03-02 Impact factor: 8.989
Authors: Cecilie Wium; Erlend T Aasheim; Thor Ueland; Annika E Michelsen; Per M Thorsby; Ingegerd F Larsen; Peter A Torjesen; Pål Aukrust; Kåre I Birkeland Journal: BMC Endocr Disord Date: 2013-10-22 Impact factor: 2.763
Authors: Christian Herder; Marja-Liisa Nuotio; Sonia Shah; Stefan Blankenberg; Eric J Brunner; Maren Carstensen; Christian Gieger; Harald Grallert; Antti Jula; Mika Kähönen; Johannes Kettunen; Mika Kivimäki; Wolfgang Koenig; Kati Kristiansson; Claudia Langenberg; Terho Lehtimäki; Kari Luotola; Carola Marzi; Christian Müller; Annette Peters; Holger Prokisch; Olli Raitakari; Wolfgang Rathmann; Michael Roden; Marko Salmi; Katharina Schramm; Daniel Swerdlow; Adam G Tabak; Barbara Thorand; Nick Wareham; Philipp S Wild; Tanja Zeller; Aroon D Hingorani; Daniel R Witte; Meena Kumari; Markus Perola; Veikko Salomaa Journal: Diabetes Date: 2014-06-26 Impact factor: 9.461