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

Diabetes Care. 2020 Oct;43(10):2581-2587. doi: 10.2337/dc20-0460. Epub 2020 Jul 31.

Abstract

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-h mixed-meal tolerance test (MTT) before the intervention and at 1 year of follow-up, and cohort II also completed a 3-h lipid test (LT). Cohort III underwent a 3-h oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion (IIGI) 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 1 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 IIGI).

Conclusions: The meal-related response of circulating succinate in patients with obesity and type 2 diabetes is recovered after metabolic surgery.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bariatric Surgery*
  • Blood Glucose / metabolism
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / surgery*
  • Diagnostic Techniques, Endocrine / standards
  • Eating / physiology*
  • Female
  • Follow-Up Studies
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood
  • Male
  • Meals
  • Middle Aged
  • Obesity, Morbid / blood
  • Obesity, Morbid / complications
  • Obesity, Morbid / surgery*
  • Reference Values
  • Succinic Acid / blood*
  • Succinic Acid / standards
  • Young Adult

Substances

  • Blood Glucose
  • Insulin
  • Succinic Acid

Associated data

  • figshare/10.2337/figshare.12621884
  • ISRCTN/ISRCTN14104758