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 including 88 obese patients with diabetes assigned to RYGB or SG based on clinical criteria. RESULTS 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] mmol/L vs. 64.1 [52.5-82.9] mmol/L; P = 0.018). Moreover, succinate concentrations were significantly decreased 1 year after surgery (58.9 [46.4-82.4] mmol/L vs. 46.0 [35.8-65.3] mmol/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. CONCLUSIONS 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.

Head and neck squamous cell carcinoma (HNSCC) is characterized by high rates of mortality and treatment-related morbidity, underscoring the urgent need for innovative and safe treatment strategies and diagnosis practices. Mitochondrial dysfunction is a hallmark of cancer and can lead to the accumulation of tricarboxylic acid cycle intermediates, such as succinate, which function as oncometabolites. In addition to its role in cancer development through epigenetic events, succinate is an extracellular signal transducer that modulates immune response, angiogenesis and cell invasion by activating its cognate receptor SUCNR1. Here, we explored the potential value of the circulating succinate and related genes in HNSCC diagnosis and prognosis. We determined the succinate levels in the serum of 66 pathologically confirmed, untreated patients with HNSCC and 20 healthy controls. We also surveyed the expression of the genes related to succinate metabolism and signaling in tumoral and nontumoral adjacent tissue and in normal mucosa from 50 patients. Finally, we performed immunohistochemical analysis of SUCNR1 in mucosal samples. The results showed that the circulating levels of succinate were higher in patients with HNSCC than in the healthy controls. Additionally, the expression of SUCNR1, HIF-1α, succinate dehydrogenase (SDH) A, and SDHB was higher in the tumor tissue than in the matched normal mucosa. Consistent with this, immunohistochemical analysis revealed an increase in SUCNR1 protein expression in tumoral and nontumoral adjacent tissue. High SUCNR1 and SDHA expression levels were associated with poor locoregional control, and the locoregional recurrence-free survival rate was significantly lower in patients with high SUCNR1 and SDHA expression than in their peers with lower levels (77.1% [95% CI: 48.9–100.0] vs. 16.7% [95% CI: 0.0–44.4], p = 0.018). Thus, the circulating succinate levels are elevated in HNSCC and high SUCNR1/SDHA expression predicts poor locoregional disease-free survival, identifying this oncometabolite as a potentially valuable noninvasive biomarker for HNSCC diagnosis and prognosis.