Abstract
AIMS: Type 2 diabetes (T2D) is characterized by its clinical heterogeneity. Newly described T2D subphenotypes, each with distinct metabolic and co-morbidity risk profiles, may enable a more personalized care. This study examined whether these subphenotypes can predict outcomes in patients undergoing metabolic and bariatric surgery (MBS). MATERIALS AND METHODS: A total of 233 people with T2D from four clinical centres undergoing MBS were retrospectively assigned to T2D subphenotypes based on the Ahlqvist methodology. The primary outcome was T2D remission at 2 years; secondary outcomes included changes in HOMA2-%B, HOMA2-IR, and total body weight loss (%TWL). Intraoperative liver biopsies were evaluated for metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH). RESULTS: All participants were classified as mild obesity-related diabetes (MOD) (62.2%), severe insulin-resistant diabetes (SIRD) (19.7%), or SIDD (18.1%). At 2 years, diabetes remission was lower in severe insulin-deficient diabetes (SIDD) (36.7%) than MOD (79.3%) and SIRD (97.2%; p < 0.001). SIDD had lower BMI (38.3 vs. 45.2 and 43.2 kg/m(2); p < 0.001) and worse beta-cell function (HOMA2-%B, 92.4 vs. 131.5 vs. 164; p = 0.010), with highest HOMA2-IR in SIRD (6.0 ± 3.4 vs. 4.4 ± 2.8 vs. 3.6 ± 1.9; p < 0.001). %TWL was similar across subphenotypes. SIDD showed higher baseline MASH prevalence (60.5% vs. 46.3% vs. 46.3%). CONCLUSION: T2D subphenotypes respond differently to T2D remission after MBS with SIDD showing a significantly lower remission rate than MOD and SIRD at 2 years. Considering metabolic status in treatment decisions may improve patient outcomes.