Cobalamin Intake and Related Biomarkers: Examining Associations With Mortality Risk Among Adults With Type 2 Diabetes in NHANES.

Diabetes care
Q1
Dec 2021
Citations:43
Influential Citations:5
Observational Studies (Human)
83
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Methods
Design: prospective cohort analysis of NHANES data. Participants: 3,277 adults aged ≥20 years with type 2 diabetes; mean age 59.3 years; 51.7% men. Follow-up through 31 December 2015 (median 7.02 years). Analysis used survey-weighted Cox proportional hazards regression to estimate hazard ratios for all-cause and cause-specific mortality, adjusting for demographics, lifestyle factors, comorbidities, diabetes-related variables, metformin use, duration of diabetes, UACR, eGFR, HbA1c, and serum cobalamin/MMA as appropriate.
Intervention
Self-reported use of cobalamin (Vitamin B12)–containing dietary supplements in the past 30 days; dosage and duration not reported.
Results
Serum cobalamin, dietary cobalamin intake, and cobalamin supplement use were not associated with reduced all-cause mortality in adults with type 2 diabetes, regardless of metformin use. Doubling methylmalonic acid (MMA) was associated with higher all-cause mortality (HR 1.31; 95% CI 1.18–1.45) and higher cardiac mortality (HR 1.38; 95% CI 1.14–1.67; P < 0.001). When categorized by MMA and B12, hazard ratios for all-cause mortality were 1.00 (reference), 0.98 (0.75–1.28), 1.49 (1.16–1.92), and 1.96 (1.38–2.78), respectively, with higher risk in the MMA-high/B12-high group and strongest in metformin nonusers. Among those with MMA >250 nmol/L and B12 >400 pg/mL, nonusers had markedly higher all-cause mortality (HR ~2.09; 95% CI 1.55–2.80). The association persisted after multivariable adjustment and was more pronounced in nonmetformin users. Overall, findings do not support mortality benefits from increasing cobalamin intake or serum levels; impaired cobalamin sensitivity (MMA accumulation with high B12) is linked to higher mortality risk, especially among nonmetformin users.
Limitations
Dietary cobalamin intake was estimated from 1–2 24-hour recalls, which may not reflect habitual intake. MMA was measured in plasma and/or serum across NHANES cycles, with potential cross-assay comparability issues. Two different serum cobalamin assays were used across cycles (Bio-Rad 1999–2004; Roche 2011–2014), which may affect comparability. Observational design with potential residual confounding; results may not generalize beyond NHANES participants or establish causality.

Abstract

OBJECTIVE Despite that periodical monitoring of cobalamin (vitamin B12) in metformin-treated patients with diabetes is recommended, cobalamin-associated mortality benefits or risks remain unclear. We investigated the association between cobalamin int...