Subphenotype-dependent benefits of bariatric surgery for individuals at risk for type 2 diabetes

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Objective Bariatric surgery (BS) is an effective treatment option for individuals with obesity and type 2 diabetes (T2D). However, whether outcomes in subtypes of individuals at risk for T2D and/or comorbidities (Tübingen Clusters) differ, is unknown. Of these, clusters 5 and 6 (C5, C6) are high-risk clusters for developing T2D and/or comorbidities, while cluster 4 (C4) is a low-risk cluster. We investigated BS outcomes, hypothesizing high-risk clusters benefit most due to great potential for metabolic improvement. Research Design and Methods We allocated participants without T2D but at risk for T2D, defined by elevated BMI, to the Tübingen Clusters. Participants had normal glucose regulation or prediabetes according to American Diabetes Association criteria. Two cohorts underwent BS: A discovery (Lille, France) and a replication cohort (Rome, Italy). A control cohort (Tübingen, Germany) received behavioral modification counseling. Main outcomes included glucose regulation and prediabetes remission. Results In the discovery cohort, 15.0% of participants (n=121) were allocated to C4, 22.3% (n=180) to C5, and 62.4% (n=503) to C6. Relative body weight loss was similar between all clusters, however C5 most strongly reduced insulin resistance and improved beta-cell function. Prediabetes remission rate was lowest in low-risk C4 and highest in high-risk C5. Individuals from high-risk clusters changed to low-risk clusters in all BS cohorts but not in the control cohort. Conclusions Participants in C5 had the highest benefit from BS in terms of improvement in insulin resistance, beta-cell function and prediabetes remission. This novel classification might help identify individuals who will benefit specifically from BS.

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