Data-driven cluster analysis of adults with prediabetes: Findings from the Japan diabetes prevention study

IF 3.6 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes Investigation Pub Date : 2026-06-01 Epub Date: 2026-04-17 DOI:10.1111/jdi.70302

Naoki Sakane, Kaoru Takahashi, Akiko Suganuma, Masayuki Domichi, Kazuyo Tsushita, Hideshi Kuzuya

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引用次数: 0

Abstract

Aim

To identify distinct metabolic subtypes among Japanese adults with prediabetes and examine their association with type 2 diabetes (T2D) risk and response to lifestyle interventions.

Methods

Data from 295 adults with impaired glucose tolerance (mean age 50.4 ± 14.6 years) enrolled in the Japanese Diabetes Prevention Program, a randomized controlled trial with up to 6 years of follow-up, were analyzed. Participants with a history of diabetes, gastrectomy, or exercise contraindications were excluded from the study. K-means clustering (k = 2–5) was applied to baseline indices, including HbA1c, HOMA-β, HOMA-IR, and HDL-cholesterol. Principal component analysis (PCA) was used for interpretation. Incident T2D was defined as a repeat 75-g OGTT. Kaplan–Meier and Cox models were adjusted for baseline HbA1c estimated cumulative incidence and hazard ratios (HRs).

Results

Three clusters emerged at k = 3, and PCA (two components explaining 68.0% of the variance) clearly separated the clusters based on insulin resistance and glycemic indices. Cluster 1, Metabolically Resilient Prediabetes (n = 127, MRP), showed the most favorable metabolic profile and lowest T2D risk. Cluster 2, Insulin-Insufficient Prediabetes (n = 109, IIP), exhibited reduced β-cell function and the highest T2D risk, but derived the greatest benefit from lifestyle intervention (adjusted HR 0.40, 95% CI 0.17–0.95, P < 0.05). Cluster 3, Severe Insulin-Resistant Prediabetes (SIRP; n = 59), displayed obesity-related insulin resistance and an intermediate risk.

Conclusions

Unsupervised clustering identified three biologically distinct prediabetic subtypes that differed in diabetes risk and intervention responsiveness, supporting a precision prevention framework for Japanese adults with prediabetes.

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数据驱动的糖尿病前期成人聚类分析：来自日本糖尿病预防研究的发现

目的：在日本成年糖尿病前期患者中识别不同的代谢亚型，并研究其与2型糖尿病（T2D）风险和生活方式干预反应的关系。方法：对日本糖尿病预防项目（一项长达6年随访的随机对照试验）中295名糖耐量受损的成年人（平均年龄50.4±14.6岁）的数据进行分析。有糖尿病史、胃切除术史或运动禁忌症的参与者被排除在研究之外。k -均值聚类（k = 2-5）应用于基线指标，包括HbA1c、HOMA-β、HOMA- ir和hdl -胆固醇。采用主成分分析（PCA）进行解释。事件T2D定义为重复75-g OGTT。Kaplan-Meier和Cox模型调整基线HbA1c估计累积发生率和风险比（hr）。结果：在k = 3时出现了三个聚类，PCA（两个分量解释68.0%的方差）根据胰岛素抵抗和血糖指数清晰地分离了聚类。第1组，代谢弹性前驱糖尿病（n = 127， MRP），显示出最有利的代谢特征和最低的T2D风险。聚类2，胰岛素不足前驱糖尿病（n = 109， IIP），表现出β细胞功能降低和T2D风险最高，但从生活方式干预中获益最大（调整HR 0.40, 95% CI 0.17-0.95， P）。结论：无监督聚类鉴定出三种生物学上不同的前驱糖尿病亚型，它们在糖尿病风险和干预反应性方面存在差异，支持日本成人前驱糖尿病的精确预防框架。

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来源期刊

Journal of Diabetes Investigation ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

9.40%

发文量

218

审稿时长

6-12 weeks

期刊介绍： Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).