Journal
DIABETES
Volume 67, Issue 6, Pages 1200-1205Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db17-1268
Keywords
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Categories
Funding
- European Union [LSHM_CT_2006_037197]
- German Federal Ministry of Education and Research (BMBF)
- State of Brandenburg
- Regional Government of Navarre
- Instituto de Salud Carlos III [PIE14/00045]
- Health Research Fund (FIS) of the Spanish Ministry of Health
- Navarre Regional Government
- Swedish Research Council
- Novo Nordisk
- Swedish Diabetes Association
- Swedish Heart-Lung Foundation
- Spanish Ministry of Health, Murcia Regional Government [6236]
- German Cancer Aid
- BMBF
- Cancer Research UK [C8221/A19170]
- Medical Research Council [MR/M012190/1]
- Medical Research Council
- Cancer Research UK
- German Cancer Research Center (DKFZ)
- Danish Cancer Society
- Regional Government of Asturias
- Vasterboten County Council
- Spanish Ministry of Health network RTICCC (ISCIII) [RD12/0036/0018]
- FEDER funds/European Regional Development Fund (ERDF)
- Generalitat de Catalunya [AGAUR 2014SGR726]
- Dutch Ministry of Health, Welfare and Sport
- Netherlands Cancer Registry
- LK Research Funds
- Dutch Prevention Funds
- Dutch ZON (Zorg Onderzoek Nederland)
- World Cancer Research Fund (WCRF)
- Statistics Netherlands
- NL Agency [IGE05012]
- Board of the University Medical Center Utrecht
- VWS Research Fund
- NKR Research Fund
- LK Research Fund
- WCRF
- Sicilian Regional Government
- L'Associazione Iblea per la Ricerca Epidemiologica-Un'organizzazione Non Lucrativa di Utilita Sociale
- Imperial College Biomedical Research Centre
- MRC [MC_UU_12015/5, MC_UU_12015/1, MR/N003284/1] Funding Source: UKRI
- Cancer Research UK [14136, 16491] Funding Source: researchfish
- Medical Research Council [G0401527, MC_UU_12015/5, G1000143, MR/N003284/1, MC_UU_12015/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0617-10149, NF-SI-0512-10114, NF-SI-0512-10135] Funding Source: researchfish
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Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. Weaimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 mu g/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.
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