Chaterina Sujana1,2, Cornelia Huth2,3, Astrid Zierer2, Sophie Meesters2, Julie Sudduth-Klinger4,5, Wolfgang Koenig6,7,8, Christian Herder3,9, Annette Peters2,3,7, Barbara Thorand10,3. 1. Institute for Medical InformaticsBiometry and Epidemiology, Ludwig-Maximilians Universität, Munich, Germany. 2. Institute of Epidemiology IIHelmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. 3. German Center for Diabetes Research (DZD)Munich-Neuherberg, Germany. 4. Tethys BioscienceEmeryville, California, USA. 5. HDF Comprehensive Cancer CenterUniversity of California San Francisco, San Francisco, California, USA. 6. Deutsches Herzzentrum MünchenTechnische Universität München, Munich, Germany. 7. German Centre for Cardiovascular Research (DZHK)Partner Site Munich Heart Alliance, Munich, Germany. 8. Department of Internal Medicine II-CardiologyUniversity of Ulm Medical Center, Ulm, Germany. 9. Institute for Clinical DiabetologyGerman Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 10. Institute of Epidemiology IIHelmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany thorand@helmholtz-muenchen.de.
Abstract
OBJECTIVE: We investigated the association of circulating fetuin-A with incident T2D particularly examining potential sex differences. Additionally, we determined whether putative associations were independent of subclinical inflammation, adiponectin and liver fat content. DESIGN: Case-cohort study plus systematic meta-analysis. METHODS: We investigated the association between baseline fetuin-A levels and incident T2D in the MONICA/KORA Augsburg study using Cox proportional hazards analyses. Furthermore, we conducted a systematic review within PubMed and EMBASE and pooled association estimates of eligible studies with the MONICA/KORA Augsburg data using a DerSimonian-Laird random effects model. RESULTS: Within MONICA/KORA Augsburg, 930 participants developed incident T2D (median follow-up: 14 years). We observed a significant association between fetuin-A and T2D risk after multivariable adjustment including C-reactive protein and adiponectin. The strength of the association was similar in males and females (P value for sex interaction >0.55). Seven eligible published studies were identified in addition to the MONICA/KORA Augsburg study for the meta-analysis. The pooled hazard ratio (95% CI) for incident T2D per 1 standard deviation (s.d.) increment of fetuin-A was 1.24 (1.14-1.34) for the multivariable adjusted model. Our sex-stratified meta-analysis yielded relative risk estimates per 1 s.d. of 1.19 (1.04-1.38) in males and 1.29 (1.15-1.46) in females. Further individual adjustment for subclinical inflammation, adiponectin and liver fat content had almost no impact on the strength of the association. CONCLUSIONS: Higher fetuin-A levels are associated with incident T2D in both males and females independently of subclinical inflammation, adiponectin and liver fat content.
OBJECTIVE: We investigated the association of circulating fetuin-A with incident T2D particularly examining potential sex differences. Additionally, we determined whether putative associations were independent of subclinical inflammation, adiponectin and liver fat content. DESIGN: Case-cohort study plus systematic meta-analysis. METHODS: We investigated the association between baseline fetuin-A levels and incident T2D in the MONICA/KORA Augsburg study using Cox proportional hazards analyses. Furthermore, we conducted a systematic review within PubMed and EMBASE and pooled association estimates of eligible studies with the MONICA/KORA Augsburg data using a DerSimonian-Laird random effects model. RESULTS: Within MONICA/KORA Augsburg, 930 participants developed incident T2D (median follow-up: 14 years). We observed a significant association between fetuin-A and T2D risk after multivariable adjustment including C-reactive protein and adiponectin. The strength of the association was similar in males and females (P value for sex interaction >0.55). Seven eligible published studies were identified in addition to the MONICA/KORA Augsburg study for the meta-analysis. The pooled hazard ratio (95% CI) for incident T2D per 1 standard deviation (s.d.) increment of fetuin-A was 1.24 (1.14-1.34) for the multivariable adjusted model. Our sex-stratified meta-analysis yielded relative risk estimates per 1 s.d. of 1.19 (1.04-1.38) in males and 1.29 (1.15-1.46) in females. Further individual adjustment for subclinical inflammation, adiponectin and liver fat content had almost no impact on the strength of the association. CONCLUSIONS: Higher fetuin-A levels are associated with incident T2D in both males and females independently of subclinical inflammation, adiponectin and liver fat content.
Authors: Nels C Olson; Margaret F Doyle; Colleen M Sitlani; Ian H de Boer; Stephen S Rich; Sally A Huber; Alan L Landay; Russell P Tracy; Bruce M Psaty; Joseph A Delaney Journal: J Clin Endocrinol Metab Date: 2020-03-01 Impact factor: 5.958