Metabolic subtypes identify Japanese adults with prediabetes at highest or lowest T2D risk

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Journal of diabetes investigation Published June 3, 2026 Medically reviewed June 3, 2026 Study authors: Sakane Naoki, Takahashi Kaoru, Suganuma Akiko, Domichi Masayuki, Tsushita Kazuyo, Kuzuya Hideshi PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Note metabolic subtypes to identify Japanese adults with prediabetes at highest or lowest T2D risk

This randomized controlled trial enrolled 295 Japanese adults with impaired glucose tolerance within the Japanese Diabetes Prevention Program. The study population was stratified into three metabolic subtypes to evaluate incident type 2 diabetes risk. Follow-up duration extended up to 6 years.

Participants were assigned to lifestyle intervention or a comparator group, though the specific comparator was not reported. The primary outcome measured incident type 2 diabetes. Secondary outcomes included metabolic subtypes and response to lifestyle interventions.

Results indicated that Cluster 1 (MRP) showed the lowest T2D risk, while Cluster 2 (IIP) showed the highest T2D risk. Cluster 3 (SIRP) showed intermediate risk. Absolute numbers were Cluster 1: n=127, Cluster 2: n=109, and Cluster 3: n=59. The benefit from lifestyle intervention was greatest in Cluster 2 (IIP), with an adjusted hazard ratio of 0.40. The 95% CI was 0.17-0.95, and the P value was less than 0.05.

Safety data, including adverse events, serious adverse events, discontinuations, and tolerability, were not reported. Key limitations included the lack of reported comparator details and absence of p-value or confidence interval reporting for the primary cluster comparison. Funding or conflicts of interest were not reported. These results support a precision prevention framework for Japanese adults with prediabetes.

Study Details

Study typeRct

EvidenceLevel 2

PublishedJun 2026

PMID41995253

View Original 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.