Subphenotype-Dependent Benefits of Bariatric Surgery for Individuals at Risk for Type 2 Diabetes.

Summary

Across discovery and replication bariatric cohorts, relative weight loss was similar among Tübingen subphenotypes, but high-risk Cluster 5 experienced the largest improvements in insulin resistance, β-cell function, and the highest prediabetes remission rates. High-risk individuals often shifted to lower-risk clusters after surgery, an effect not seen in lifestyle controls.

Key Findings

• Relative weight loss was similar across clusters, but insulin resistance reduction and β-cell function improvement were strongest in Cluster 5.
• Prediabetes remission was lowest in low-risk Cluster 4 and highest in high-risk Cluster 5.
• High-risk clusters shifted to lower-risk clusters after bariatric surgery in both cohorts, but not in the lifestyle control cohort.

Clinical Implications

Use metabolic clustering (e.g., Tübingen Clusters) to identify high-risk individuals (C5) most likely to derive insulin resistance and β-cell benefits and achieve prediabetes remission after bariatric surgery. Incorporate subphenotyping into preoperative evaluation and shared decision-making.

Limitations

• Observational design without randomization may allow residual confounding
• Follow-up duration and long-term hard outcomes (e.g., incident T2D) not detailed in the abstract

Future Directions

Prospective randomized or pragmatic trials stratified by metabolic clusters to test surgery versus medical/lifestyle therapy on incident T2D and cardiovascular outcomes; development of clinically deployable clustering tools.