Correlations between circulating methylmalonic acid levels and all-cause and cause-specific mortality among patients with diabetes

Abstract

AimsEvidence regarding serum methylmalonic acid (MMA) levels and mortality in individuals with diabetes is limited. This study aimed to evaluate the correlation between MMA and all-cause and cause-specific deaths in patients with diabetes.Materials and methodsThis is a population-based cohort study based on data from both the National Health and Nutrition Examination Survey (NHANES) and National Death Index from 1999 to 2014. We assessed the association of serum MMA concentrations with mortality using Cox proportional hazard models after adjusting for lifestyle, demographic factors, and comorbidities.ResultsAmong the 3,097 participants, 843 mortalities occurred during a median follow-up of 4.42 years. There were 242 deaths due to cardiovascular disease (CVD) and 131 cancer-associated deaths. After multivariate adjustment, elevated serum MMA levels were markedly correlated with a high risk of all-cause, CVD-, and cancer-related deaths. Each one-unit increase in the natural log-transformed MMA level correlated with increased risk of all-cause mortality (2.652 times), CVD mortality risk (3.153 times), and cancer-related mortality risk (4.514). Hazard ratios (95% confidence intervals [CIs]) after comparing participants with MMA < 120 and ≥250 nmol/L were 2.177 (1.421–3.336) for all-cause mortality, 3.560 (1.809–7.004) for CVD mortality, and 4.244 (1.537–11.721) for cancer mortality.ConclusionHigher serum MMA levels were significantly associated with higher all-cause, CVD, and cancer mortality. These findings suggest that maintaining lower MMA status may lower mortality risk in individuals with diabetes.

Association between blood methylmalonic acid and chronic kidney disease in the general US population: insights from multi-cycle National Health and Nutrition Examination Survey (NHANES)

“…Elevated circulating MMA levels have been reported in several diseases in adults, such as coronary heart disease, kidney dysfunction, and diabetes ( 23 - 25 ). Moreover, emerging evidence suggested that elevated level of blood MMA may serve as a promising biomarker for predicting adverse outcomes in chronic diseases ( 12 , 13 , 26 ).…”

Association of Serum Vitamin B12 and Circulating Methylmalonic Acid Levels with All-Cause and Cardiovascular Disease Mortality among Individuals with Chronic Kidney Disease

“…Another prospective study conducted on two cohorts demonstrated that elevated MMA levels were associated with a higher risk of acute myocardial infarction (AMI) and mortality in patients with a suspected or confirmed CHD [ 39 ]. MMA is a potential risk factor of CVD, diabetic complications, and dementias, and higher MMA levels have been associated with all-cause mortality, cancer mortality, and CVD mortality among individuals with diabetes [ 10 , 22 ]. Similar results were confirmed in our study, where there was a significant association found between the MMA levels and all-cause and cardiovascular mortality.…”

“…The relationship between vitamin B 12 and mortality has previously been explored in the elderly [ 16 , 17 ], hospitalized [ 18 , 19 ], hemodialysis patients [ 20 ], and general population [ 21 ]. And the relationship between MMA and mortality has previously been explored in patients with diabetes and the general population [ 10 , 22 , 23 ]. However, the relationship between MMA and vitamin B 12 concentrations and mortality in patients with CKD has not been studied.…”

Sexual Dimorphism in Mitochondrial Dysfunction and Diabetes Mellitus: Evidence from Population-Based Cohort Study

“…Both cobalamin de ciency and mitochondrial dysfunction were found to be involved in sex differences and the pathogenesis of diabetes [10,11,18,19]. Other and our recent study found that serum MMA was associated with increased mortality risk independent of cobalamin levels, and about half patients with MMA accumulation could not attribute to cobalamin de ciency [18,20,21]. Thus, MMA maybe a potentially modi able marker re ecting mitochondrial dysfunction to explain the worsened prognosis in males with diabetes.…”