Long-Term Use of Antibiotics and Risk of Type 2 Diabetes in Women: Results from the Nurses' Health Studies

Background: There is accumulating evidence suggesting that long-term antibiotic use may alter the gut microbiome which has, in turn, been linked to type 2 diabetes. We undertake this study to investigate whether antibiotic use was associated with increased risk of type 2 diabetes. Methods: This prospective cohort study included U.S. women free of diabetes, cardiovascular disease and cancer in the Nurses' Health Study (NHS 2004-2012) and NHS II (2005-2013). We evaluated the overall duration of antibiotics use in the past four years and at different ages (NHS: age 20-39, 40-59, and 60+; NHS II: age 20-39, 40-49, and 50+) and subsequent diabetes risk with a time-dependent COX proportional hazards model. Findings: Pooled analyses of NHS and NHS II (1 476 cases, 379 143 person-years) revealed that a longer duration of antibiotic use in the past 4 years was significantly associated with higher risk of diabetes (Ptrend = 0·002). As compared with non-users, participants who received antibiotics treatment for a medium duration of 15 days to 2 months (HR 1.29, 95% CI 1·11 to 1·51) or long duration of over 2 months (HR 1·27, 95% CI 1·12 to 1·58) had significantly higher risk. We also noted significant positive associations between antibiotic use duration at age 40-49 and the diabetes risk in NHS II (Ptrend < 0·0001) and between antibiotic use at age 60+ and diabetes risk in NHS (Ptrend = 0·01). Interpretation: A longer duration of antibiotic use in recent years and in middle or older age was associated with increased risk of type 2 diabetes in women. Funding Statement: This study was supported by the startup grant for the 100 Top Talents Program, The Seventh Affiliated Hospital, Sun Yat-sen University (392012). The NHS and NHS II were supported by the National Cancer Institute (UM1 CA176726, and UM1 CA186107), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK58845, DK112940). Declaration of Interests: The authors declared that there was no potential conflicts of interest relevant to this article. Ethics Approval Statement: The NHS and NHS II were approved by the Human Research Committee at the Brigham and Women’s Hospital, Boston, MA. All participants provided written informed consent.