Methylamine metabolites and progression to kidney failure in type 2 diabetes: An Asian and European prospective study

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism Pub Date : 2025-04-30 DOI:10.1016/j.diabet.2025.101658

Pierre-Jean Saulnier , Jian-Jun Liu , Mikael Croyal , Joe de Keizer , Jiexun Wang , Huili Zheng , Robert G. Nelson , Stéphanie Ragot , Sylvia Liu , Jean-Michel Halimi , Bertrand Cariou , Su Chi Lim , Samy Hadjadj , Singapore KTPH-DKD study group, France SURDIAGENE study group

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引用次数: 0

Abstract

Aim

Unlike trimethylamine N-oxide (TMAO), the role of methylamine pathway metabolites in diabetic kidney disease (DKD) remains unclear. We investigated the association of circulating methylamines with progression of DKD in a prospective cohort study of patients with type 2 diabetes of two different ethnic backgrounds.

Methods

We analyzed two independent cohorts: a European-origin cohort (SURDIAGENE France; n = 1,357) and an Asian-origin cohort (Khoo Teck Puat Hospital-DKD [KTPH-DKD] Singapore, n = 1,868). The primary composite renal outcome in SURDIAGENE was sustained doubling of serum creatinine or kidney failure with replacement therapy (KFRT), while the secondary outcome was 40% renal function loss (RFL40). In KTPH-DKD, KFRT was the primary outcome. Baseline betaine, carnitine, choline, trimethylamine and TMAO concentrations were measured in plasma by mass-spectrometry. Cox regression models were used to estimate the risk of DKD progression, adjusting for demographics, clinical parameters, and comorbidities.

Results

Over a median follow-up of 7.1 years (IQR 4.5-10.7), we registered 75 composite renal outcomes in SURDIAGENE and over 10.7 years (IQR 7.0-11.8), 149 KFRT in KTPH-DKD. Choline was the only consistently associated with progression of DKD in both cohorts: HR [95%CI] per 1 SD = 1.29 [1.02;1.62], P = 0.033 for composite renal outcome, 1.11 [1.01;1.23], P = 0.028 for RFL40 in SURDIAGENE, and 1.84 [1.30;2.61], P < 0.001 for KFRT in KTPH-DKD.

Conclusion

Plasma choline is an independent risk factor for DKD progression in two independent type 2 diabetes populations. Interventional trials are needed to assess whether reducing dietary choline intake could mitigate severe renal outcomes in type 2 diabetes.

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甲胺代谢物与2型糖尿病肾衰竭进展：一项亚洲和欧洲的前瞻性研究

目的：与三甲胺n -氧化物（TMAO）不同，甲胺途径代谢物在糖尿病肾病（DKD）中的作用尚不清楚。我们在一项针对两种不同种族背景的2型糖尿病患者的前瞻性队列研究中调查了循环甲胺与DKD进展的关系。方法：我们分析了两个独立的队列：一个是欧洲裔队列(SURDIAGENE France；n= 1357)和一个亚裔队列（新加坡Khoo Teck Puat Hospital-DKD [KTPH-DKD]， n= 1868）。SURDIAGENE的主要综合肾脏结局是替代治疗（KFRT）时血清肌酐持续翻倍或肾功能衰竭，而次要结局是40%肾功能丧失（RFL40）。在KTPH-DKD中，KFRT是主要转归。用质谱法测定血浆中甜菜碱、肉碱、胆碱、三甲胺和氧化三甲胺的基线浓度。Cox回归模型用于估计DKD进展的风险，并根据人口统计学、临床参数和合并症进行调整。结果：在中位随访7.1年（IQR 4.5-10.7）中，SURDIAGENE组记录了75例复合肾脏结局，在10.7年（IQR 7.0-11.8）中，KTPH-DKD组记录了149例KFRT。在两个队列中，胆碱是唯一与DKD进展一致的相关因素：每1 SD的HR [95%CI] = 1.29[1.02;1.62]，复合肾结局的P = 0.033,1.11 [1.01;1.23]，SURDIAGENE组RFL40的P = 0.028，KTPH-DKD组KFRT的P = 0.028，KTPH-DKD组KFRT的P = 1.84 [1.30;2.61],P < 0.001。结论：血浆胆碱是两个独立2型糖尿病人群中DKD进展的独立危险因素。需要进行干预性试验来评估减少饮食胆碱摄入量是否可以减轻2型糖尿病患者严重的肾脏结局。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes & metabolism 医学-内分泌学与代谢

CiteScore

12.00

自引率

4.20%

发文量

审稿时长

13 days

期刊介绍： A high quality scientific journal with an international readership Official publication of the SFD, Diabetes & Metabolism, publishes high-quality papers by leading teams, forming a close link between hospital and research units. Diabetes & Metabolism is published in English language and is indexed in all major databases with its impact factor constantly progressing. Diabetes & Metabolism contains original articles, short reports and comprehensive reviews.