钴胺素摄入量及相关生物标志物：NHANES 中 2 型糖尿病成人死亡率风险相关因素分析。
Cobalamin Intake and Related Biomarkers: Examining Associations With Mortality Risk Among Adults With Type 2 Diabetes in NHANES.
机构信息
Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.
出版信息
Diabetes Care. 2022 Feb 1;45(2):276-284. doi: 10.2337/dc21-1674.
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.
目的
尽管建议定期监测接受二甲双胍治疗的糖尿病患者的钴胺素（维生素 B12），但与钴胺素相关的死亡率获益或风险仍不清楚。我们使用接受或未接受二甲双胍治疗的糖尿病成年人的钴胺素摄入量及其相关生物标志物与死亡率风险之间的关系进行了调查。
研究设计和方法
本研究纳入了来自国家健康和营养检查调查（NHANES）的 3277 名 2 型糖尿病成人患者，随访至 2015 年 12 月 31 日。使用加权 Cox 比例风险回归估计死亡率风险的危险比（HR）和 95%置信区间。
结果
在 3277 名参与者中，中位随访 7.02 年期间发生了 865 例全因死亡。无论是否接受二甲双胍治疗，全因死亡率与血清钴胺素或食物或钴胺素补充剂的摄入量之间均无明显关系（每项 P ≥ 0.120）。作为钴胺素缺乏标志物的甲基丙二酸（MMA）水平翻倍与全因死亡率（HR 1.31 [95%CI 1.18-1.45]，P<0.001）和心脏死亡率（HR 1.38 [95%CI 1.14-1.67]，P=0.001）显著相关。通过将二元 B12 低值/高值和 MMA 低值/高值（临界值：钴胺素 400 pg/mL，MMA 250 nmol/L）组合评估钴胺素敏感性。具有降低的钴胺素敏感性（MMAhighB12high）的患者死亡率风险最高。MMA 低值 B12 低值、MMA 低值 B12 高值、MMA 高值 B12 低值和 MMA 高值 B12 高值组的全因死亡率的多变量校正 HR（95%CI）分别为 1.00（参考）、0.98（0.75-1.28）、1.49（1.16-1.92）和 1.96（1.38-2.78）。这种关联在非二甲双胍使用者中尤为显著。
结论
血清和饮食钴胺素与死亡率降低无关。钴胺素敏感性降低与全因和心脏死亡率显著相关，尤其是在非二甲双胍使用者中。
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