title: Diet-dependent acid load and type 2 diabetes: pooled results from three prospective cohort studies.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Epidemiology, Erasmus MC, Room NA2903, PO Box 2040, 3000, CA, Rotterdam, the Netherlands. j.c.kiefte-dejong@erasmusmc.nl.|Department of Global Public Health, Leiden University College, The Hague, the Netherlands. j.c.kiefte-dejong@erasmusmc.nl.|Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA. j.c.kiefte-dejong@erasmusmc.nl.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Kiefte-de Jong
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.|Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Mu
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Gary C
authors.initials: GC
authors.lastname: Curhan
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Josiemer
authors.initials: J
authors.lastname: Mattei
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Vasanti S
authors.initials: VS
authors.lastname: Malik
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Forman
authors.affiliation: Department of Epidemiology, Erasmus MC, Room NA2903, PO Box 2040, 3000, CA, Rotterdam, the Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.|Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
mesh_terms: D000138:Acidosis / Q000378:metabolism; D000143:Acids / Q000008:administration & dosage / Q000378:metabolism*; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004032:Diet / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000143:Acids
keywords: Acid–base balance; Dietary acid load; Glucose intolerance; Insulin resistance