Shanjie Wang1,2, Ye Wang1,2, Xin Wan1,2, Junchen Guo1,2, Yiying Zhang3, Maoyi Tian4,5, Shaohong Fang1,2, Bo Yu1,2. 1. Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China. 2. The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China. 3. Department of Epidemiology and Biostatistics, School of Public Health, Jiamusi University, Jiamusi, China. 4. School of Public Health, Harbin Medical University, Harbin, China. 5. The George Institute for Global Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.
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 intake and related biomarkers and mortality risk in adults with diabetes using metformin or not. RESEARCH DESIGN AND METHODS: This study included 3,277 adults with type 2 diabetes from the National Health and Nutrition Examination Survey (NHANES) and followed up until 31 December 2015. Weighted Cox proportional hazards 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 or intake of 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 (HR 1.38 [95% CI 1.14-1.67], P = 0.001) mortality. Cobalamin sensitivity was assessed by the combination of binary B12low/high and MMAlow/high (cutoff values: cobalamin 400 pg/mL, MMA 250 nmol/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.
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 intake and related biomarkers and mortality risk in adults with diabetes using metformin or not. RESEARCH DESIGN AND METHODS: This study included 3,277 adults with type 2 diabetes from the National Health and Nutrition Examination Survey (NHANES) and followed up until 31 December 2015. Weighted Cox proportional hazards 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 or intake of 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 (HR 1.38 [95% CI 1.14-1.67], P = 0.001) mortality. Cobalamin sensitivity was assessed by the combination of binary B12low/high and MMAlow/high (cutoff values: cobalamin 400 pg/mL, MMA 250 nmol/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.
Authors: Phuc Le; Alexander Chaitoff; Anita D Misra-Hebert; Wen Ye; William H Herman; Michael B Rothberg Journal: Diabetes Care Date: 2020-03-31 Impact factor: 19.112