Impaired succinate response to a mixed meal in obesity and type 2 diabetes is normalized after metabolic surgery
<div><b><i>Objective</i></b> 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. <b><i><br></i></b></div><div><b><i>Research Design and</i></b> <b><i>Methods</i></b> Cohort I comprised 45 patients with morbid obesity and type 2 diabetes (BMI 39.4±1.9 kg/m<sup>2</sup>) undergoing metabolic surgery. Cohort II was a confirmatory cohort of 13 patients (BMI 39.3±1.4 kg/m<sup>2</sup>) undergoing gastric bypass surgery. Cohort III comprised 15 healthy subjects (BMI 26.4±0.5 kg/m<sup>2</sup>). 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. </div> <p><b><i>Results</i></b><i> </i>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 <i>per se</i> stimulated a plasma succinate response (p=0.0004), but its response was greater in the OGTT (p=0.02; OGTT <i>versus</i> ISO). </p> <p><b><i>Conclusions</i></b><b> </b>The<b> </b>meal-related response of circulating succinate in patients with obesity and type 2 diabetes is recovered after metabolic surgery.</p>