Postprandial Metabolism After Bariatric Surgery in Type 2 Diabetes
CB4
1 other identifier
interventional
18
1 country
1
Brief Summary
Bariatric surgery procedures have now been firmly demonstrated to lead to significant improvement and even, in many cases, complete reversal of abnormal glucose homeostasis in type 2 diabetes (T2D). Various surgery procedures are can be performed to induce weight loss. The most striking anti-diabetic effects are observed with biliopancreatic diversion with duodenal switch (BPD-DS), followed by Roux-in-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). The first two procedures induce both a restriction of energy intake and a low absorption of dietary fatty acids while the latter exclusively targets energy intake restriction. The investigator and others have shown that improvement of T2D occurs within days after BPD-DS or RYGB in the vast majority of patients, prior to any significant weight loss. This very rapid metabolic recovery is explained by a normalization of β-cell function after meal challenges and ameliorated hepatic insulin sensitivity. The investigator and others have shown that these acute anti-diabetic effects are mostly recapitulated by matched caloric restriction, independent of changes in gastrointestinal hormones, showing the importance of gastrointestinal-derived energy fluxes for acute diabetes control. Muscle insulin sensitivity, on the other hand, improves more slowly in association with weight loss, demonstrating the heterogeneous metabolic response of the various organs to BPD-DS. Some preliminary studies also demonstrate a rapid reduction of NEFA levels and production rate upon i.v. administration of lipids during euglycemic hyperinsulinemic clamps. This very rapid improvement in NEFA tolerance strongly suggests that adipose tissue storage of circulating fatty acids also improves very rapidly, prior to any significant weight loss, after BPD-DS. It may also suggest an acceleration of oxidative fatty acid metabolism in organs such as the liver, the heart and/or skeletal muscles. Studies of the rapid metabolic changes after bariatric surgery conducted thus far rapidly improved the understanding of the fundamental pathogenic defects of T2D. However, much remains to be understood about the acute changes in gastrointestinal-derived metabolic fluxes, organ-specific metabolic responses to bariatric surgery and their relationship with the reversal of T2D. Using in vivo methodological approaches, the investigator proposes to investigate the early organ-specific changes in dietary fatty acid metabolism in response to BPD-DS vs. SG and their relation to improved systemic changes in glucose homeostasis, insulin sensitivity and β-cell function in patients with T2D.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable type-2-diabetes
Started Aug 2015
Longer than P75 for not_applicable type-2-diabetes
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2015
CompletedFirst Submitted
Initial submission to the registry
June 23, 2016
CompletedFirst Posted
Study publicly available on registry
June 28, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2019
CompletedMay 17, 2022
May 1, 2022
4.3 years
June 23, 2016
May 16, 2022
Conditions
Outcome Measures
Primary Outcomes (4)
glucose metabolism
will be determined using tracers of glucose
2 years
dietary fatty acid uptake
assessed using PET/CT method with oral administration of 18FTHA
2 years
whole body inter-organ partitioning
assessed using PET/CT method with oral administration of 18FTHA
2 years
lipid metabolism
will be determined using tracers of fatty acids
2 years
Secondary Outcomes (7)
Dietary fatty acid oxidation rate
2 years
Total oxidation rate
2 years
Hormonal responses
2 years
Insulin sensitivity
2 years
Insulin secretion index (ISI)
2 years
- +2 more secondary outcomes
Study Arms (4)
Before DBP-DS surgery
OTHERAfter DBP-DS surgery
EXPERIMENTALIt is a bariatric surgery. BPD consists in the exclusion of the duodenum from the alimentary tract with re-anastomosis of the blind loop 100 to 150 cm proximal to the ileo-coecal valve. This leads to bypass of the biliopancreatic secretions towards the distal small intestine, resulting in fat malabsorption. BPD also entails a distal gastrectomy to avoid the occurrence of peptic ulceration of the gastrointestinal anastomosis.
Before SG surgery
OTHERAfter SG surgery
EXPERIMENTALIt is a bariatric surgery where the stomach is reduced to about 15% of its original size, by surgical removal of a large portion of the stomach along the greater curvature.
Interventions
will be consumed over 30 minutes with \[U-13C\]-palmitate (0.2 g mixed in the liquid meal) and H2-glucose
a dynamic and whole body PET acquisition will be performed on a thoraco-abdominal segment, 150 minutes after an oral administration of 18FTHA
i.v. administration of \[7,7,8,8-2H\]-palmitate (in 25% human albumin) from time -60 to 360 min.
will be performed every hour throughout the protocol along with exhaled breath collection
Eligibility Criteria
You may qualify if:
- Four groups of 11 subjects each: obese subjects with T2D or with normal glucose tolerance undergoing either BPD-DS or SG for treatment of obesity. T2D and control subjects will be matched for age (± 3 years), BMI (± 2 kg/m2) and gender across both BPD-DS and SG.
You may not qualify if:
- presence of overt cardiovascular disease, as assessed by history, physical exam, and abnormal EKG;
- treatment with a fibrate, a thiazolidinedione, a beta-blocker or other drugs known to affect lipid or carbohydrate metabolism (except statins, sulfonylurea, metformin, and other antihypertensive agents that can be temporarily stopped prior to the protocols);
- presence of liver or renal disease, uncontrolled thyroid disorder or other major illnesses;
- smoking (\>1 cigarette/day) and/or consumption of more than 2 alcoholic beverages per day;
- prior history or current fasting plasma cholesterol level \> 7 mmol/l or fasting TG \> 6 mmol/l;
- any other contraindication to temporarily stop current medications for hyperglycemia, lipids, or hypertension.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Université de Sherbrookelead
- Laval Universitycollaborator
Study Sites (1)
Centre de recherche du CHUS
Sherbrooke, Quebec, J1H 5N4, Canada
Related Publications (1)
Carreau AM, Noll C, Blondin DP, Frisch F, Nadeau M, Pelletier M, Phoenix S, Cunnane SC, Guerin B, Turcotte EE, Lebel S, Biertho L, Tchernof A, Carpentier AC. Bariatric Surgery Rapidly Decreases Cardiac Dietary Fatty Acid Partitioning and Hepatic Insulin Resistance Through Increased Intra-abdominal Adipose Tissue Storage and Reduced Spillover in Type 2 Diabetes. Diabetes. 2020 Apr;69(4):567-577. doi: 10.2337/db19-0773. Epub 2020 Jan 8.
PMID: 31915151DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
André Carpentier, MD
Université de Sherbrooke
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Tenured professor
Study Record Dates
First Submitted
June 23, 2016
First Posted
June 28, 2016
Study Start
August 1, 2015
Primary Completion
December 1, 2019
Study Completion
December 1, 2019
Last Updated
May 17, 2022
Record last verified: 2022-05