Preoperative Circulating Succinate Levels as a Biomarker for Diabetes Remission After Bariatric Surgery
Ceperuelo-Mallafré V (1,2), Llauradó G (2,3), Keiran N (1,2), Benaiges E (1,2), Astiarraga B (1,2,4), Martínez L (1), Pellitero S (2,5), González-Clemente JM (2,6), Rodríguez A (7), Fernández-Real JM (4), Lecube A (8), Megía A (1,2), Vilarrasa N (2,9), Vendrell J (10,2,11), Fernández-Veledo S (12,2).
This study was conducted to determine the potential use of baseline circulating succinate to predict type 2 diabetes remission after bariatric surgery.
RESEARCH DESIGN AND METHODS:
Forty-five obese patients with diabetes were randomly assigned to Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or laparoscopic greater curvature plication. Anthropometric parameters were evaluated, and a complete biochemical analysis, including circulating serum succinate concentrations, was performed at baseline and 1 year after surgery. The results were externally validated in a second cohort of 88 obese patients with diabetes assigned to RYGB or SG based on clinical criteria.
Succinate baseline concentrations were an independent predictor of diabetes remission after bariatric surgery. Patients achieving remission after 1 year had lower levels of baseline succinate (47.8 [37.6-64.6] µmol/L vs. 64.1 [52.5-82.9] µmol/L; P = 0.018). Moreover, succinate concentrations were significantly decreased 1 year after surgery (58.9 [46.4-82.4] µmol/L vs. 46.0 [35.8-65.3] µmol/L, P = 0.005). In multivariate analysis, the best logistic regression model showed that baseline succinate (odds ratio [OR] 11.3, P = 0.031) and the type of surgery (OR 26.4, P = 0.010) were independently associated with remission. The C-statistic for this model was 0.899 (95% CI 0.809-0.989) in the derivation cohort, which significantly improved the prediction of remission compared with current available scores, and 0.729 (95% CI 0.612-0.846) in the validation cohort. Interestingly, patients had a different response to the type of surgery according to baseline succinate, with significant differences in remission rates.
Circulating succinate is reduced after bariatric surgery. Baseline succinate levels have predictive value for diabetes remission independently of previously described presurgical factors and improve upon the current available scores to predict remission.