American Diabetes Association
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Metabolomic signatures of long-term coffee consumption and risk of type 2 diabetes in women

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posted on 2020-08-11, 16:09 authored by Dong Hang, Oana A. Zeleznik, Xiaosheng He, Marta Guasch-Ferre, Xia Jiang, Jun Li, Liming Liang, A. Heather Eliassen, Clary B. Clish, Andrew T. Chan, Zhibin Hu, Hongbing Shen, Kathryn M. Wilson, Lorelei A. Mucci, Qi Sun, Frank B. Hu, Walter C. Willett, Edward L. Giovannucci, Mingyang Song
Objective: Coffee may protect against multiple chronic diseases, particularly type 2 diabetes, but the mechanisms remain unclear.

Research Design and Methods: Leveraging dietary and metabolomic data in two large cohorts of women (the Nurses’ Health Study I and II), we identified and validated plasma metabolites associated with coffee intake in 1595 women. We then evaluated the prospective association of coffee-related metabolites with diabetes risk and the added predictivity of these metabolites for diabetes in two nested case-control studies (n=457 cases and 1371 controls).

Results: Of 461 metabolites, 34 were identified and validated to be associated with total coffee intake, including 13 positive associations (primarily trigonelline, polyphenol metabolites, and caffeine metabolites) and 21 inverse associations (primarily triacylglycerols and diacylglycerols). These associations were generally consistent for caffeinated and decaffeinated coffee, except for caffeine and its metabolites that were only associated with caffeinated coffee intake. The three cholesteryl esters positively associated with coffee intake showed inverse associations with diabetes risk, whereas the 12 metabolites negatively associated with coffee (five diacylglycerols and seven triacylglycerols) showed positive associations with diabetes. Adding the 15 diabetes-associated metabolites to classical risk factors-based prediction model increased the C-statistic from 0.79 (95% CI: 0.76, 0.83) to 0.83 (95% CI: 0.80, 0.86) (P<0.001). Similar improvement was observed in the validation set.

Conclusion: Coffee consumption is associated with widespread metabolic changes, among which lipid metabolites may be critical for the anti- diabetes benefit of coffee. Coffee-related metabolites might help improve prediction of diabetes, but further validation studies are needed.


This work was supported by the American Cancer Society Mentored Research Scholar Grant (MRSG-17-220-01 - NEC to MS); by the U.S. National Institutes of Health grants (UM1 CA186107 to MJ Stampfer; R01 CA49449 to SE Hankinson; U01 CA176726 and R01 CA050385 to WCW and AHE; P01 CA087969 and R01 CA163451 to SS Tworoger; R01 AR057327 to EW Karlson; R01 NS045893 and R01 NS089619 to A Ascherio; P01 CA087969 to RM Tamimi; K24 DK098311, R01 CA137178, R01 CA202704, R01 CA176726 to ATC; K99 CA215314, R00 CA215314 to MS; R01 DK112940 to FBH); by the Department of Defense (W81XWH-12-1-0561); and by grants from National Natural Science Foundation of China (81973127 to DH) and Natural Science Foundation of Jiangsu Province (BK20190083 to DH). ATC is a Stuart and Suzanne Steele MGH Research Scholar.


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