Abstract
<a><b>Objective</b></a> Despite periodical monitoring of cobalamin (vitamin B12) in metformin-treated diabetic patients is recommended, the cobalamin-associated mortality benefits or risks remains unclear. We investigated the association between cobalamin intake and related biomarkers and mortality risk in diabetic adults using metformin or not. <p><b>Methods</b> This study included 3,277 adults with type 2 diabetes from NHANES and followed up until December 31, 2015. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality risk.</p> <p><b>Results </b>Among 3,277 participants, 865 all-cause deaths occurred during a median follow-up of 7.02 years. There was no robust relationship between all-cause mortality and serum cobalamin, intakes from foods or cobalamin supplements regardless of metformin treatment (each p ≥0.120). The doubling of methylmalonic acid (MMA, a cobalamin-deficiency marker) was significantly associated with higher all-cause (HR 1.31 95%CI 1.18–1.45, p <0.001) and cardiac mortality (HR 1.38 95%CI 1.14–1.67, p =0.001). Cobalamin sensitivity was assessed by the combination of binary B12<sub>low/high</sub> and MMA<sub>low/high</sub> (cutoff values: cobalamin 400 pg/ml and MMA 250nmol/L). Patients with decreased cobalamin sensitivity (MMA<sub>high</sub>B12<sub>high</sub>) had the highest mortality risk. The multivariable-adjusted HRs (95%CIs) of all-cause mortality in MMA<sub>low</sub>B12<sub>low</sub>, MMA<sub>low</sub>B12<sub>high</sub>, MMA<sub>high</sub>B12<sub>low</sub>, and MMA<sub>high</sub>B12<sub>high</sub> groups were<sub> </sub>1.00 (reference), 0.98 (0.75–1.28), 1.49 (1.16–1.92), and 1.96 (1.38–2.78), respectively. That association was especially significant in metformin nonusers.</p> <p><b>Conclusions</b> Serum and dietary cobalamin were not associated with reduced mortality. Decreased cobalamin sensitivity was significantly associated with all-cause and cardiac mortality, particularly among metformin nonusers.</p>
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