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.
This study was supported by grants from the Spanish Ministry of Economy and Competitiveness (PI14/00228 and PI17/0153 to JV, SAF2015 and RTI2018-093919-B-I00 to SF-V, PI14/01997 and PI17/01556 to NV, and PI18/00516 to AM, co-financed by the European Regional Development (ERDF). The Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM) (CB07708/0012) is an initiative of the Instituto de Salud Carlos III.