Kiefte-de Jong, Jessica C.Li, YanpingChen, MuCurhan, GaryMattei, JosiemerMalik, VasantiForman, JohnFranco, Oscar H.Hu, Frank2018-04-192018Kiefte-de Jong, Jessica C., Yanping Li, Mu Chen, Gary C. Curhan, Josiemer Mattei, Vasanti S. Malik, John P. Forman, Oscar H. Franco, and Frank B. Hu. 2018. “Diet-dependent acid load and type 2 diabetes: pooled results from three prospective cohort studies.” Diabetologia 60 (2): 270-279. doi:10.1007/s00125-016-4153-7. http://dx.doi.org/10.1007/s00125-016-4153-7.http://nrs.harvard.edu/urn-3:HUL.InstRepos:35982125Aims/hypothesis Studies suggest a potential link between low-grade metabolic acidosis and type 2 diabetes. A western dietary pattern increases daily acid load but the association between diet-dependent acid load and type 2 diabetes is still unclear. This study aimed to assess whether diet-dependent acid load is associated with the risk of type 2 diabetes. Methods: We examined the association between energy-adjusted net endogenous acid production (NEAP), potential renal acid load (PRAL) and animal protein-to-potassium ratio (A:P) on incident type 2 diabetes in 67,433 women from the Nurses’ Health Study, 84,310 women from the Nurses’ Health Study II and 35,743 men from the Health Professionals’ Follow-up Study who were free from type 2 diabetes, cardiovascular disease and cancer at baseline. Study-specific HRs were estimated using Cox proportional hazards models with time-varying covariates and were pooled using a random effects meta-analysis. Results: We documented 15,305 cases of type 2 diabetes during 4,025,131 person-years of follow-up. After adjustment for diabetes risk factors, dietary NEAP, PRAL and A:P were positively associated with type 2 diabetes (pooled HR [95% CI] for highest (Q5) vs lowest quintile (Q1): 1.29 [1.22, 1.37], ptrend <0.0001; 1.29 [1.22, 1.36], ptrend <0.0001 and 1.32 [1.24, 1.40], ptrend <0.0001 for NEAP, PRAL and A:P, respectively). These results were not fully explained by other dietary factors including glycaemic load and dietary quality (HR [95% CI] for Q5 vs Q1: 1.21 [1.09, 1.33], ptrend <0.0001; 1.19 [1.08, 1.30] and 1.26 [1.17, 1.36], ptrend <0.0001 for NEAP, PRAL and A:P, respectively). Conclusions/interpretation This study suggests that higher diet-dependent acid load is associated with an increased risk of type 2 diabetes. This association is not fully explained by diabetes risk factors and overall diet quality.en-USAcid–base balanceDietary acid loadGlucose intoleranceInsulin resistanceJournal Article2018-04-1910.1007/s00125-016-4153-7