TY  - JOUR
A1  - Kroeger, Janine
A1  - Meidtner, Karina
A1  - Stefan, Norbert
A1  - Guevara, Marcela
A1  - Kerrison, Nicola D.
A1  - Ardanaz, Eva
A1  - Aune, Dagfinn
A1  - Boeing, Heiner
A1  - Dorronsoro, Miren
A1  - Dow, Courtney
A1  - Fagherazzi, Guy
A1  - Franks, Paul W.
A1  - Freisling, Heinz
A1  - Gunter, Marc J.
A1  - Maria Huerta, Jose
A1  - Kaaks, Rudolf
A1  - Key, Timothy J.
A1  - Khaw, Kay Tee
A1  - Krogh, Vittorio
A1  - Kuehn, Tilman
A1  - Mancini, Francesca Romana
A1  - Mattiello, Amalia
A1  - Nilsson, Peter M.
A1  - Olsen, Anja
A1  - Overvad, Kim
A1  - Palli, Domenico
A1  - Ramon Quiros, J.
A1  - Rolandsson, Olov
A1  - Sacerdote, Carlotta
A1  - Sala, Nuria
A1  - Salamanca-Fernandez, Elena
A1  - Sluijs, Ivonne
A1  - Spijkerman, Annemieke M. W.
A1  - Tjonneland, Anne
A1  - Tsilidis, Konstantinos K.
A1  - Tumino, Rosario
A1  - van der Schouw, Yvonne T.
A1  - Forouhi, Nita G.
A1  - Sharp, Stephen J.
A1  - Langenberg, Claudia
A1  - Riboli, Elio
A1  - Schulze, Matthias B.
A1  - Wareham, Nicholas J.
T1  - Circulating Fetuin-A and Risk of Type 2 Diabetes
BT  - a mendelian randomization analysis
JF  - Diabetes : a journal of the American Diabetes Association
N2  - 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.
Y1  - 2018
U6  - https://doi.org/10.2337/db17-1268
SN  - 0012-1797
SN  - 1939-327X
VL  - 67
IS  - 6
SP  - 1200
EP  - 1205
PB  - American Diabetes Association
CY  - Alexandria
ER  -