TY  - JOUR
A1  - Zheng, Ju-Sheng
A1  - Luan, Jian'an
A1  - Sofianopoulou, Eleni
A1  - Imamura, Fumiaki
A1  - Stewart, Isobel D.
A1  - Day, Felix R.
A1  - Pietzner, Maik
A1  - Wheeler, Eleanor
A1  - Lotta, Luca A.
A1  - Gundersen, Thomas E.
A1  - Amiano, Pilar
A1  - Ardanaz, Eva
A1  - Chirlaque, Maria-Dolores
A1  - Fagherazzi, Guy
A1  - Franks, Paul W.
A1  - Kaaks, Rudolf
A1  - Laouali, Nasser
A1  - Mancini, Francesca Romana
A1  - Nilsson, Peter M.
A1  - Onland-Moret, N. Charlotte
A1  - Olsen, Anja
A1  - Overvad, Kim
A1  - Panico, Salvatore
A1  - Palli, Domenico
A1  - Ricceri, Fulvio
A1  - Rolandsson, Olov
A1  - Spijkerman, Annemieke M. W.
A1  - Sanchez, Maria-Jose
A1  - Schulze, Matthias Bernd
A1  - Sala, Nuria
A1  - Sieri, Sabina
A1  - Tjonneland, Anne
A1  - Tumino, Rosario
A1  - van der Schouw, Yvonne T.
A1  - Weiderpass, Elisabete
A1  - Riboli, Elio
A1  - Danesh, John
A1  - Butterworth, Adam S.
A1  - Sharp, Stephen J.
A1  - Langenberg, Claudia
A1  - Forouhi, Nita G.
A1  - Wareham, Nicholas J.
T1  - Plasma vitamin C and type 2 diabetes
BT  - genome-wide association study and Mendelian randomization analysis in European populations
JF  - Diabetes care
N2  - OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.

RESEARCH DESIGN AND METHODS: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. 

RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 x 10(-8)), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).

CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
Y1  - 2020
U6  - https://doi.org/10.2337/dc20-1328
SN  - 0149-5992
SN  - 1935-5548
VL  - 44
IS  - 1
SP  - 98
EP  - 106
PB  - American Diabetes Association
CY  - Alexandria
ER  - 
TY  - JOUR
A1  - Dietrich, Stefan
A1  - Jacobs, Simone
A1  - Zheng, Ju-Sheng
A1  - Meidtner, Karina
A1  - Schwingshackl, Lukas
A1  - Schulze, Matthias Bernd
T1  - Gene-lifestyle interaction on risk of type 2 diabetes
BT  - A systematic review
JF  - Obesity reviews : an official journal of the International Association for the Study of Obesity
N2  - The pathophysiological influence of gene-lifestyle interactions on the risk to develop type 2 diabetes (T2D) is currently under intensive research. This systematic review summarizes the evidence for gene-lifestyle interactions regarding T2D incidence. MEDLINE, EMBASE, and Web of Science were systematically searched until 31 January 2019 to identify publication with (a) prospective study design; (b) T2D incidence; (c) gene-diet, gene-physical activity, and gene-weight loss intervention interaction; and (d) population who are healthy or prediabetic. Of 66 eligible publications, 28 reported significant interactions. A variety of different genetic variants and dietary factors were studied. Variants at TCF7L2 were most frequently investigated and showed interactions with fiber and whole grain on T2D incidence. Further gene-diet interactions were reported for, eg, a western dietary pattern with a T2D-GRS, fat and carbohydrate with IRS1 rs2943641, and heme iron with variants of HFE. Physical activity showed interaction with HNF1B, IRS1, PPAR gamma, ADRA2B, SLC2A2, and ABCC8 variants and weight loss interventions with ENPP1, PPAR gamma, ADIPOR2, ADRA2B, TNF alpha, and LIPC variants. However, most findings represent single study findings obtained in European ethnicities. Although some interactions have been reported, their conclusiveness is still low, as most findings were not yet replicated across multiple study populations.
KW  - diet
KW  - gene-lifestyle interaction
KW  - incident type 2 diabetes
KW  - physical activity
KW  - weight loss intervention
Y1  - 2019
U6  - https://doi.org/10.1111/obr.12921
SN  - 1467-7881
SN  - 1467-789X
VL  - 20
IS  - 11
SP  - 1557
EP  - 1571
PB  - Wiley
CY  - Hoboken
ER  -