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

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posted on 03.12.2021, 16:02 by Shanjie Wang, Ye Wang, Xin Wan, Junchen Guo, Yiying Zhang, Maoyi Tian, Shaohong Fang, Bo Yu
Objective 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.

Methods 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.

Results 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 B12low/high and MMAlow/high (cutoff values: cobalamin 400 pg/ml and MMA 250nmol/L). Patients with decreased cobalamin sensitivity (MMAhighB12high) had the highest mortality risk. The multivariable-adjusted HRs (95%CIs) of all-cause mortality in MMAlowB12low, MMAlowB12high, MMAhighB12low, and MMAhighB12high groups were 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.

Conclusions 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.


This manuscript was completed independently. Dr Yu was supported by the National Key R&D Program (No. 2016YFC1301100) and the National Natural Science Foundation of China (No.81827806). Dr Fang was supported by the National Natural Science Foundation of China (No. 82170262 and 81870353).