title: Serum levels of interleukin-22, cardiometabolic risk factors and incident type 2 diabetes: KORA F4/FF4 study.
abstract: Interleukin-22 (IL-22) has beneficial effects on body weight, insulin resistance and inflammation in different mouse models, but its relevance for the development of type 2 diabetes in humans is unknown. We aimed to identify correlates of serum IL-22 levels and to test the hypothesis that higher IL-22 levels are associated with lower diabetes incidence.
  
  
  
  Cross-sectional associations between serum IL-22, cardiometabolic risk factors and glucose tolerance status were investigated in 1107 persons of the population-based KORA F4 study. The prospective association between serum IL-22 and incident type 2 diabetes was assessed in 504 initially non-diabetic study participants in both the KORA F4 study and its 7-year follow-up examination KORA FF4, 76 of whom developed diabetes.
  
  
  
  Male sex, current smoking, lower HDL cholesterol, lower estimated glomerular filtration rate and higher serum interleukin-1 receptor antagonist were associated with higher IL-22 levels after adjustment for confounders (all P < 0.05). Serum IL-22 showed no associations with glucose tolerance status, prediabetes or type 2 diabetes. Baseline serum IL-22 levels (median, 25th/75th percentiles) for incident type 2 diabetes cases and non-cases were 6.28 (1.95; 12.35) and 6.45 (1.95; 11.80) pg/ml, respectively (age and sex-adjusted P = 0.744). The age and sex-adjusted OR (95% CI) per doubling of IL-22 for incident type 2 diabetes of 1.02 (0.85; 1.23) was almost unchanged after consideration of further confounders.
  
  
  
  High serum levels of IL-22 were positively rather than inversely associated with several cardiometabolic risk factors. However, these associations did not translate into an increased risk for type 2 diabetes. Thus, our data argue against the utility of IL-22 as biomarker for prevalent or incident type 2 diabetes in humans, but identify potential determinants of IL-22 levels which merits further research in the context of cardiovascular diseases.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany. Christian.herder@ddz.uni-duesseldorf.de.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany. Christian.herder@ddz.uni-duesseldorf.de.
authors.forename: Christian
authors.identifier: 0000-0002-2050-093X
authors.initials: C
authors.lastname: Herder
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Kannenberg
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Carstensen-Kirberg
authors.affiliation: German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Huth
authors.affiliation: German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.affiliation: Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.|German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.affiliation: German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.affiliation: German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rathmann
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007378:Interleukins / Q000097:blood*; D016014:Linear Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D011446:Prospective Studies; D065840:Protective Factors; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation; D000097043:Interleukin-22
chemical_list: D015415:Biomarkers; D007378:Interleukins; D000097043:Interleukin-22
keywords: Cardiometabolic risk; Cohort study; Cytokine; Inflammation; Interleukin-22; Type 2 diabetes