Identification of pre-diabetes subphenotypes for type 2 diabetes, related vascular complications and mortality.

IF 3.7 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

BMJ Open Diabetes Research & Care Pub Date : 2025-06-09 DOI:10.1136/bmjdrc-2024-004803

Chaiwat Washirasaksiri, Nutsakol Borrisut, Varisara Lapinee, Tullaya Sitasuwan, Rungsima Tinmanee, Chayanis Kositamongkol, Pinyapat Ariyakunaphan, Watip Tangjittipokin, Nattachet Plengvidhya, Weerachai Srivanichakorn

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Abstract

Introduction: Pre-diabetes comprises diverse subphenotypes linked to varying complications, type 2 diabetes, and mortality outcomes. This study aimed to explore these outcomes across different pre-diabetes subphenotypes.

Research design and methods: The dataset included adults without type 2 diabetes with baseline HbA1c and fasting plasma glucose (FPG) measurements from Siriraj Hospital, Bangkok, Thailand. The participants were classified into six subphenotypes via the k-means clustering method on the basis of age, body mass index, FPG, HbA1c, high-density lipoprotein cholesterol and alanine aminotransferase levels. The incidences of type 2 diabetes, long-term vascular complications and mortality were compared among subphenotypes over a median follow-up of 8.8 years, employing Kaplan-Meier curves and Cox regression analysis adjusted for sex, statin use and hypertension status.

Results: Among the 4915 participants (mean age 60.1±10.1 years; 54.6% female), six clusters emerged: cluster 1, low risk (n=650; 13.2%); cluster 2, mild dysglycemia elderly (n=791; 16.1%); cluster 3, severe dysglycemia obese (n=1127; 22.9%); cluster 4, mild dysglycemia obese (n=963; 19.7%); cluster 5, severe dysmetabolic obese (n=337; 6.9%); and cluster 6, severe dysglycemia elderly (n=1042; 21.2%). Clusters were classified into diabetes risk subgroups: low risk (clusters 1 and 4) and high risk (clusters 3 and 5). Cluster 6 exhibited the highest risk, with significantly increased incidences of macrovascular complications (adjusted HR 2.22, 1.51-3.27) and type 2 diabetes (1.73, 1.42-2.12). In contrast, cluster 4 demonstrated the lowest risk, with significantly decreased incidences of new chronic kidney disease (0.65, 0.44-0.96), microvascular complications (0.62, 0.43-0.89) and mortality (0.25, 0.10-0.63).

Conclusions: Our pre-diabetes phenotyping approach effectively provides valuable insights into the risk of type 2 diabetes, vascular complications and mortality in individuals with pre-diabetes. Those with high-risk phenotypes should be prioritized for type 2 diabetes and cardiovascular interventions to mitigate risks.

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2型糖尿病前期亚表型的鉴定，相关血管并发症和死亡率。

前驱糖尿病包括与不同并发症、2型糖尿病和死亡率结果相关的不同亚表型。本研究旨在探讨不同糖尿病前期亚表型的这些结果。研究设计和方法：数据集包括来自泰国曼谷Siriraj医院的基线HbA1c和空腹血糖（FPG）测量的无2型糖尿病的成年人。根据年龄、体重指数、FPG、HbA1c、高密度脂蛋白胆固醇和丙氨酸转氨酶水平，通过k-means聚类方法将参与者分为6个亚表型。在中位随访8.8年期间，采用Kaplan-Meier曲线和Cox回归分析，比较不同亚表型患者2型糖尿病、长期血管并发症和死亡率的发生率，并调整性别、他汀类药物使用和高血压状况。结果：4915名参与者(平均年龄60.1±10.1岁；54.6%女性)，出现6个聚类：聚类1，低风险(n=650；13.2%);第2组，轻度血糖异常的老年人(n=791；16.1%);第3组，重度血糖异常肥胖(n=1127；22.9%);第4组，轻度血糖异常肥胖(n=963；19.7%);第5组，重度代谢异常肥胖(n=337；6.9%);第6组为重度血糖异常老年人(n=1042；21.2%)。群集被分为糖尿病风险亚组：低风险（群集1和4）和高风险（群集3和5）。聚类6风险最高，大血管并发症（调整HR 2.22, 1.51-3.27）和2型糖尿病（调整HR 1.73, 1.42-2.12）发生率显著增加。相比之下，聚类4的风险最低，新发慢性肾脏疾病（0.65,0.44-0.96）、微血管并发症（0.62,0.43-0.89）和死亡率（0.25,0.10-0.63）均显著降低。结论：我们的糖尿病前期表型分析方法有效地为糖尿病前期患者的2型糖尿病风险、血管并发症和死亡率提供了有价值的见解。高危表型患者应优先接受2型糖尿病和心血管干预以降低风险。

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

BMJ Open Diabetes Research & Care Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

9.30

自引率

2.40%

发文量

123

审稿时长

18 weeks

期刊介绍： BMJ Open Diabetes Research & Care is an open access journal committed to publishing high-quality, basic and clinical research articles regarding type 1 and type 2 diabetes, and associated complications. Only original content will be accepted, and submissions are subject to rigorous peer review to ensure the publication of high-quality — and evidence-based — original research articles.