Barbara Kollerits1, Claudia Lamina1, Cornelia Huth2,3, Pedro Marques-Vidal4, Stefan Kiechl5, Ilkka Seppälä6,7, Jackie Cooper8, Steven C Hunt9,10, Christa Meisinger2,3, Christian Herder3,11, Ludmilla Kedenko12, Johann Willeit5, Barbara Thorand2,3, Doreen Dähnhardt1, Doris Stöckl2,3, Karin Willeit5, Michael Roden3,11,13, Wolfgang Rathmann3,14, Bernhard Paulweber12, Annette Peters2,3,15, Mika Kähönen16,17, Terho Lehtimäki6,7, Olli T Raitakari18,19, Steve E Humphries8, Peter Vollenweider4, Hans Dieplinger1,20, Florian Kronenberg21. 1. Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria. 2. Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. 3. German Center for Diabetes Research (DZD), München-Neuherberg, Germany. 4. Department of Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland. 5. Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. 6. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland. 7. Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland. 8. Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, University College London, London, U.K. 9. Cardiovascular Genetics Division, University of Utah School of Medicine, Salt Lake City, UT. 10. Department of Genetic Medicine, Weill Cornell Medicine, Doha, Qatar. 11. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 12. First Department of Internal Medicine, Paracelsus Private Medical University, Salzburg, Austria. 13. Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 14. Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 15. German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany. 16. Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland. 17. Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland. 18. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland. 19. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. 20. Vitateq Biotechnology GmbH, Innsbruck, Austria. 21. Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria florian.kronenberg@i-med.ac.at.
Abstract
OBJECTIVE: The human vitamin E-binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in line with observations in transgenic mice. We thus investigated whether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR). RESEARCH DESIGN AND METHODS: Individual-level baseline (n = 20,136) and follow-up data (n = 14,017) of eight prospective cohort studies were investigated. Study-level data were combined using random-effects meta-analyses. Main outcomes were prevalent and incident type 2 diabetes, prediabetes, and IR. Discrimination and reclassification of participants was analyzed for incident type 2 diabetes. RESULTS: Mean afamin concentrations between studies ranged from 61 to 73 mg/L. The eight studies included 1,398 prevalent and 585 incident cases of type 2 diabetes. Each increase of afamin by 10 mg/L was associated with prevalent type 2 diabetes (odds ratio [OR] 1.19 [95% CI 1.12-1.26], P = 5.96 × 10-8). Afamin was positively associated with IR assessed by HOMA-IR (β 0.110 [95% CI 0.089-0.132], P = 1.37 × 10-23). Most importantly, afamin measured at baseline was an independent predictor for 585 incident cases of type 2 diabetes (OR 1.30 [95% CI 1.23-1.38], P = 3.53 × 10-19) and showed a significant and valuable gain in risk classification accuracy when added to this extended adjustment model. CONCLUSIONS: This pooled analysis in >20,000 individuals showed that afamin is strongly associated with IR, prevalence, and incidence of type 2 diabetes independent of major metabolic risk factors or parameters. Afamin might be a promising novel marker for the identification of individuals at high risk for the development of type 2 diabetes.
OBJECTIVE: The human vitamin E-binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in line with observations in transgenic mice. We thus investigated whether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR). RESEARCH DESIGN AND METHODS: Individual-level baseline (n = 20,136) and follow-up data (n = 14,017) of eight prospective cohort studies were investigated. Study-level data were combined using random-effects meta-analyses. Main outcomes were prevalent and incident type 2 diabetes, prediabetes, and IR. Discrimination and reclassification of participants was analyzed for incident type 2 diabetes. RESULTS: Mean afamin concentrations between studies ranged from 61 to 73 mg/L. The eight studies included 1,398 prevalent and 585 incident cases of type 2 diabetes. Each increase of afamin by 10 mg/L was associated with prevalent type 2 diabetes (odds ratio [OR] 1.19 [95% CI 1.12-1.26], P = 5.96 × 10-8). Afamin was positively associated with IR assessed by HOMA-IR (β 0.110 [95% CI 0.089-0.132], P = 1.37 × 10-23). Most importantly, afamin measured at baseline was an independent predictor for 585 incident cases of type 2 diabetes (OR 1.30 [95% CI 1.23-1.38], P = 3.53 × 10-19) and showed a significant and valuable gain in risk classification accuracy when added to this extended adjustment model. CONCLUSIONS: This pooled analysis in >20,000 individuals showed that afamin is strongly associated with IR, prevalence, and incidence of type 2 diabetes independent of major metabolic risk factors or parameters. Afamin might be a promising novel marker for the identification of individuals at high risk for the development of type 2 diabetes.
Authors: Lili Niu; Philipp E Geyer; Nicolai J Wewer Albrechtsen; Lise L Gluud; Alberto Santos; Sophia Doll; Peter V Treit; Jens J Holst; Filip K Knop; Tina Vilsbøll; Anders Junker; Stephan Sachs; Kerstin Stemmer; Timo D Müller; Matthias H Tschöp; Susanna M Hofmann; Matthias Mann Journal: Mol Syst Biol Date: 2019-03-01 Impact factor: 11.429
Authors: Debby Ngo; Mark D Benson; Jonathan Z Long; Zsu-Zsu Chen; Ruiqi Wang; Anjali K Nath; Michelle J Keyes; Dongxiao Shen; Sumita Sinha; Eric Kuhn; Jordan E Morningstar; Xu Shi; Bennet D Peterson; Christopher Chan; Daniel H Katz; Usman A Tahir; Laurie A Farrell; Olle Melander; Jonathan D Mosley; Steven A Carr; Ramachandran S Vasan; Martin G Larson; J Gustav Smith; Thomas J Wang; Qiong Yang; Robert E Gerszten Journal: JCI Insight Date: 2021-03-08