Obesity, Anion Accumulation, and Anion Gap Metabolic Acidosis: A Cohort Study

Abstract

Background: Obesity is associated with low serum bicarbonate, an indicator of metabolic acidosis and a CKD risk factor. To further characterize acid-base disturbance and subclinical metabolic acidosis in this population, we examined prospective associations of body mass index (BMI) with elevated anion gap, and whether anion gap values in obesity associate with low bicarbonate. Methods: Data from adult outpatients (n = 94,448) in the Bronx, NY were collected from 2010-2018. Mixed effects models and Cox proportional hazards models were used to examine associations of BMI with elevated anion gap and anion gap metabolic acidosis, and of baseline anion gap with incident low bicarbonate and anion gap metabolic acidosis. Anion gap was defined using traditional and albumin-corrected calculations. Results: Greater BMI was associated with higher anion gap over time, and with progressively greater risk of developing an elevated anion gap (HRs for BMI ≥ 40 vs. 18-<25 kg/m2: 1.32 [95% CI: 1.23 - 1.42] for traditional and 1.74 [95% CI: 1.63 - 1.85] for corrected). Higher BMI was also associated with increased risk of developing anion gap metabolic acidosis (HR for BMI ≥ 40: 1.53 [95% CI: 1.39 - 1.69]). Among patients with obesity, higher anion gap was associated with increased risk of incident low bicarbonate (HRs for 4th vs 1st quartile: 1.29 [95% CI: 1.23 - 1.44] for traditional and 1.36 [95% CI: 1.26 - 1.48] for corrected); and higher risk of anion gap metabolic acidosis (HR for 4th vs 1st quartile 1.78 [1.59 - 1.99]). Conclusions: Obesity is characterized by unmeasured anion accumulation and acid retention or overproduction. Modest elevations in anion gap among patients with obesity are associated with previously unrecognized anion gap metabolic acidosis.