Impaired Succinate Response to a Mixed Meal in Obesity and Type 2 Diabetes is Normalized after Metabolic Surgery

Objective To explore the meal response of circulating succinate in patients with obesity and type 2 diabetes undergoing bariatric surgery, and to examine the role of gastrointestinal glucose sensing in succinate dynamics in healthy subjects.Research Design and Methods Cohort I comprised 45 patients with morbid obesity and type 2 diabetes (BMI 39.4±1.9 kg/m2) undergoing metabolic surgery. Cohort II was a confirmatory cohort of 13 patients (BMI 39.3±1.4 kg/m2) undergoing gastric bypass surgery. Cohort III comprised 15 healthy subjects (BMI 26.4±0.5 kg/m2). Cohorts I and II completed a 2-hour meal tolerance test (MTT) before the intervention and at one-year of follow-up, and cohort II also completed a 3-hour lipid test (LT). Cohort III underwent a 3-hour oral glucose tolerance test (OGTT) and an isoglycemic variable glucose infusion (ISO) study.Results In cohort I, succinate response to MTT at follow-up was greater than before the intervention (p<0.0001). This response was confirmed in cohort II with a greater increase after one year of surgery (p=0.009). By contrast, LT did not elicit a succinate response. Changes in succinate response were associated with changes in the area under the curve of glucose (r=0.417, p<0.0001) and insulin (r=0.204, p=0.002). In cohort III, glycemia per se stimulated a plasma succinate response (p=0.0004), but its response was greater in the OGTT (p=0.02; OGTT versus ISO).Conclusions The meal-related response of circulating succinate in patients with obesity and type 2 diabetes is recovered after metabolic surgery.