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.

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.

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 B12_low/high and MMA_low/high (cutoff values: cobalamin 400 pg/mL, MMA 250 nmol/L). Patients with decreased cobalamin sensitivity (MMA_highB12_high) had the highest mortality risk. The multivariable-adjusted HRs (95% CIs) of all-cause mortality in MMA_lowB12_low, MMA_lowB12_high, MMA_highB12_low, and MMA_highB12_high 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.

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.

尽管建议在二甲双胍治疗的糖尿病患者中定期监测钴胺素（维生素 B12），但与钴胺素相关的死亡率益处或风险仍不清楚。我们调查了使用或不使用二甲双胍的成年糖尿病患者的钴胺素摄入量与相关生物标志物和死亡风险之间的关系。

这项研究包括来自国家健康和营养检查调查 (NHANES) 的 3,277 名 2 型糖尿病成年人，并随访至 2015 年 12 月 31 日。加权 Cox 比例风险回归用于估计死亡风险的风险比 (HR) 和 95% CI。

在 3,277 名参与者中，865 名全因死亡发生在 7.02 年的中位随访期间。无论二甲双胍治疗如何，全因死亡率与血清钴胺素或食物摄入量或钴胺素补充剂之间没有密切关系（每个P ≥ 0.120）。甲基丙二酸 (MMA) 是一种钴胺素缺乏标志物，倍增与更高的全因 (HR 1.31 [95% CI 1.18–1.45], P < 0.001) 和心脏 (HR 1.38 [95% CI 1.14– 1.67]，P = 0.001) 死亡率。通过二元 B12_低/高和 MMA_低/高的组合评估钴胺素敏感性（截止值：钴胺素 400 pg/mL，MMA 250 nmol/L）。钴胺素敏感性降低的患者（MMA_高B12_高) 的死亡风险最高。_MMA低B12_低、MMA_低B12_高、MMA_高B12_低和 MMA_高B12_高组全因死亡率的多变量调整 HR（95% CI）分别为 1.00（参考）、0.98（0.75-1.28）、分别为 1.49 (1.16–1.92) 和 1.96 (1.38–2.78)。这种关联在非二甲双胍非使用者中尤为重要。

血清和膳食钴胺素与死亡率降低无关。降低的钴胺素敏感性与全因死亡率和心脏死亡率显着相关，尤其是在不使用二甲双胍的人群中。