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.

Acid retention may occur in the absence of overt metabolic acidosis; thus it is important to identify populations at risk. Because obesity may alter renal acid-base handling, we sought to determine whether overweight and obesity are associated with increased risk for low serum bicarbonate levels, suggesting metabolic acidosis.

Background: Obesity is a recently identified risk factor for metabolic acidosis and anion gap elevations in the absence of chronic kidney disease (CKD). Metabolic acidosis is a treatable condition with substantial adverse effects on human health. Additional investigations are needed to characterize at-risk populations and explore potential mechanisms. We hypothesized metabolic syndrome (MetS) and waist circumference (WC) would be closely associated with this pathology. Methods: Adult participants from NHANES 1999 - 2018 meeting study criteria were compiled as main (n = 31,163) and fasting (n = 12,860) cohorts. Regression models adjusted for dietary acid, estimated glomerular filtration rate (eGFR), and other factors examined associations of WC and MetS features with anion gap metabolic acidosis and its components (serum bicarbonate ≤ 23 mEq/L and anion gap > 95th percentile). Results: Greater WC and MetS features were associated with progressively lower bicarbonate, higher anion gap, and greater odds ratios (OR) of metabolic acidosis (MA) and anion gap metabolic acidosis (AGMA). Compared to the reference, participants with the highest WC had ORs for MA and AGMA of 2.26 [1.96 - 2.62] and 2.89 [1.97 - 4.21]; those with three and four vs. zero MetS features had ORs for AGMA of 2.52 [1.95 - 2.94] and 3.05 [2.16 - 3.82]. Associations of body mass index with outcomes were attenuated or absent following adjustment for WC or MetS. Findings were preserved after excluding eGFR < 90 mL/min/1.73m2 and albuminuria. A lower MA cutoff (< 22 mEq/L) raised the estimate of association between MetS and MA (OR for three and four vs zero features: 3.56 [2.53 - 5.02] and 5.44 [3.66 - 8.08]). Conclusions: Metabolic diseases are characterized by metabolic acidosis and anion gap elevations. Metabolic dysfunction may predispose patients without CKD to systemic acidosis from endogenous sources. Comprehensive acid-base analyses may be informative in patients with metabolic diseases.

No abstract