Low Serum Bicarbonate Levels Increase the Risk of All-Cause, Cardiovascular Disease, and Cancer Mortality in Type 2 Diabetes

CONTEXT: The evidence regarding bicarbonate status and mortality among diabetes is scarce. OBJECTIVE: The purpose of this study was to investigate the associations of bicarbonate concentrations with risk of all-cause, cardiovascular disease (CVD), and cancer mortality among patients with type 2 diabetes (T2D). METHODS: This study included 8163 adult diabetic patients from the National Health and Nutrition Examination Survey (NHANES), 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. The Cox proportional-risk model was used to estimate hazard ratios (HR) and 95% CIs for mortality from all causes, CVD, and cancer. The mediating effects of 11 metabolic, cardiovascular, and renal biomarkers were evaluated using a logistic regression model within a counterfactual framework. RESULTS: During 8163 person-years of follow-up, 2310 deaths were documented, including 659 CVD deaths and 399 cancer deaths. After multivariate adjustment, lower serum bicarbonate levels were significantly linearly correlated with higher all-cause, CVD, and cancer mortality: The risk of all-cause death increased by 40%, the risk of CVD death increased by 48%, and the risk of cancer death increased by 84% compared with the normal group (all P < .05). Altered levels of estimated glomerular filtration rate explained 12.10% and 16.94% of the relation between serum bicarbonate with all-cause and CVD mortality, respectively. Total cholesterol mediated 4.70% and 10.51% of the associations of all-cause and CVD mortality, respectively. CONCLUSION: Lower serum bicarbonate concentrations were significantly associated with higher all-cause, CVD, and cancer mortality. These findings suggest that maintaining adequate bicarbonate status may lower mortality risk in individuals with T2D.