title: Dietary acid load, metabolic acidosis and insulin resistance - Lessons from cross-sectional and overfeeding studies in humans.
abstract: Western diets rich in animal protein and poor in fruit and vegetables increase the body acid load, a predictor of type 2 diabetes risk. The relationships between dietary acid load, mild metabolic acidosis and insulin resistance remain unclear. The objective of this study was to assess the association between dietary acid load, body acid/base markers and peripheral insulin resistance at baseline and following a short-term overfeeding intervention in healthy individuals.
  
  
  
  In a cross-sectional study of 104 men and women, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Plasma lactate, a marker of metabolic acidosis, was assessed and acid load scores (potential renal acid load, PRAL and net endogenous acid production, NEAP) derived from diet diaries. The cohort was grouped into lean and overweight/obese and the latter further classified as insulin-sensitive (Obsen) and insulin-resistant (Obres) based on hyperinsulinemic-euglycemic clamp glucose infusion rate (GIR, top tertile vs. bottom 2 tertiles). A subset of 40 individuals participated in an overfeeding intervention (+1250 kcal/day) for 28 days and studies repeated.
  
  
  
  Obsen and Obres were matched for adiposity (BMI and fat mass, both P = 1). Fasting plasma lactate was higher in Obres (0.78 [0.63-1.14] mmol/L) compared with both lean (0.71 [0.44-0.90] mmol/L, P = 0.02) and Obsen (0.67 [0.56-0.79] mmol/L, P = 0.04) and not different between lean and Obsen (P = 0.9). Overfeeding was characterized by an increase in dietary acid load scores PRAL (P = 0.003) and NEAP (P = 0.05), a reduction in GIR necessary to maintain euglycemia (P = 0.03) and an increase in fasting plasma lactate (P = 0.02). The change in lactate was inversely associated with the change in GIR (r = -0.36, P = 0.03).
  
  
  
  Mild metabolic acidosis, measured by plasma lactate, aligns with insulin resistance independent of obesity and is induced by short-term increases in energy and dietary acid load in healthy humans. Further studies are required to determine whether buffering mild metabolic acidosis improves insulin resistance and reduces diabetes risk.
authors: School of Molecular Bioscience, The University of Sydney, NSW, Australia; Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia. Electronic address: rebeccawilliams206@gmail.com.
authors: Rebecca S
authors: RS
authors: Williams
authors: Discipline of Medicine, University of Adelaide, SA, Australia. Electronic address: leonie.heilbronn@adelaide.edu.au.
authors: Leonie K
authors: LK
authors: Heilbronn
authors: Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia. Electronic address: d.chen@garvan.org.au.
authors: Daniel L
authors: DL
authors: Chen
authors: School of Mathematics and Statistics, UNSW Australia, NSW, Australia. Electronic address: a.coster@unsw.edu.au.
authors: Adelle C F
authors: AC
authors: Coster
authors: Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia; Faculty of Medicine, UNSW Australia, NSW, Australia; Department of Endocrinology and Diabetes Center, St. Vincent's Hospital, NSW, Australia. Electronic address: j.greenfield@garvan.org.au.
authors: Jerry R
authors: JR
authors: Greenfield
authors: Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia; Faculty of Medicine, UNSW Australia, NSW, Australia. Electronic address: d.samochabonet@garvan.org.au.
authors: Dorit
authors: D
authors: Samocha-Bonet
mesh_terms: D000138:Acidosis / Q000175:diagnosis* / Q000209:etiology; D000143:Acids / Q000097:blood; D050154:Adiposity; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000209:etiology; D015930:Diet Records; D066273:Diet, Western / Q000009:adverse effects*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006963:Hyperphagia / Q000097:blood* / Q000150:complications; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D019344:Lactic Acid / Q000097:blood; D008297:Male
chemical_list: D000143:Acids; D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D019344:Lactic Acid
keywords: Adiposity; Dietary acid load; Insulin resistance; Lactate