Associations of Metabolic Syndrome and Abdominal Obesity with Anion Gap Metabolic Acidosis among US Adults.

Background: Obesity is a recently identified risk factor for metabolic acidosis and anion gap elevations in the absence of 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, 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 with the reference, participants with the highest WC had ORs for MA and AGMA of 2.26; 95% CI, 1.96 to 2.62 and 2.89; 95% CI, 1.97 to 4.21; those with three and four versus zero MetS features had ORs for AGMA of 2.52; 95% CI, 1.95 to 2.94 and 3.05; 95% CI, 2.16 to 3.82. Associations of body mass index with outcomes were attenuated or absent after adjustment for WC or MetS. Findings were preserved after excluding eGFR <90 ml/min per 1.73 m2 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; 95% CI, 2.53 to 5.02 and 5.44; 95% CI, 3.66 to 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.

Obesity and the Risk of Low Bicarbonate: A Cohort Study.

RATIONALE & OBJECTIVE: 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. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult patients (n = 96,147) visiting outpatient clinics in the Bronx, NY, between January 1, 2010, and December 31, 2015. PREDICTOR: Body mass index (BMI). OUTCOME: Low serum bicarbonate level (≤23 mEq/L). ANALYTICAL APPROACH: Longitudinal analyses were conducted using mixed-effects models to examine associations of BMI with serum bicarbonate levels over time and Cox proportional hazards models to examine associations of BMI with incident low bicarbonate levels. RESULTS: During a median follow-up of 4.4 (interquartile range, 2.3-6.3) years, patients had a median of 8 serum bicarbonate measurements and 34,539 patients developed low bicarbonate levels. Higher BMI was associated with progressively lower serum bicarbonate levels, with attenuation of the association in the highest BMI groups, suggesting a J-shaped relationship. Compared with the reference group (BMI, 18.5 to <25 kg.m2), patients with BMIs of 25 to <30, 30 to <35, 35 to <40, and ≥40 kg/m2 had HRs for incident low bicarbonate levels of 1.10 (95% CI, 1.05-1.14), 1.16 (95% CI, 1.11-1.21), 1.20 (95% CI, 1.14-1.26), and 1.15 (95% CI, 1.09-1.22). Results were similar after adjustment for serum urea nitrogen level and exclusion of patients with diabetes, hypertension, or estimated glomerular filtration rates < 60 mL/min/1.73 m2. LIMITATIONS: Arterial pH measurements were unavailable. CONCLUSIONS: Higher BMI is independently associated with progressively greater risk for developing low serum bicarbonate levels, indicating likely metabolic acidosis. Further research should explore the causes of low bicarbonate levels in patients with overweight and obesity.

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

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, New York were collected from 2010 to 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 (hazard ratio [HR] for body mass index [BMI]≥40 kg/m2 versus 18 to <25 kg/m2, 1.32; 95% confidence interval [95% CI], 1.23 to 1.42 for traditional and HR for BMI≥40 kg/m2 versus 18 to <25 kg/m2, 1.74; 95% CI, 1.63 to 1.85 for corrected). Higher BMI was also associated with increased risk of developing anion gap metabolic acidosis (HR for BMI≥40 kg/m2, 1.53; 95% CI, 1.39 to 1.69). Among patients with obesity, higher anion gap was associated with increased risk of incident low bicarbonate (HR for fourth versus first quartile, 1.29; 95% CI, 1.23 to 1.44 for traditional and HR for fourth versus first quartile, 1.36; 95% CI, 1.26 to 1.48 for corrected) and higher risk of anion gap metabolic acidosis (HR for fourth versus first quartile, 1.78; 95% CI, 1.59 to 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.

Long-term changes in quality of discharge water from abandoned underground coal mines in Uniontown Syncline, Fayette County, PA, USA.

Changes in water quality over 25 years have been documented for discharges from an extensive network of abandoned underground coal mines in the Uniontown Syncline, Fayette County, PA, USA. A baseline study of 136 mine discharges in the syncline was conducted in 1974-1975. In 1998-2000, follow-up water flow and quality monitoring was conducted at 21 selected discharges for 2 years to assess the degree of mine water-quality improvement since 1974-1975. The data from the two periods of time were compared, with consideration of differences in measurement methods. The degree and rate of water-quality improvement was found to be highly dependent on the amount and duration of flooding in the mine voids. Water quality of discharges from the substantially flooded mine voids improved significantly, going from acidic water with high sulfate and iron concentrations in 1974-1975 to alkaline water with substantially lower sulfate and iron concentrations in 1998-2000. In contrast, the water quality in the unflooded mines showed less improvement over the 25 years between studies. The water discharging from the unflooded mines in 1974-1975 was acidic with high sulfate concentrations and in 1998-2000 was still acidic but showed somewhat lower sulfate and iron concentrations, reflecting depletion of readily available pyrite. The data obtained provide insight into the potential and rate of natural amelioration of mine water quality in different abandoned underground coal mine systems.