Clinical trial NCT04782999: Effect of RYGB on Alpha- and Beta Cell Function and Sensitivity to Incretins in Patients With Type 2 Diabetes
Official title: Effect of RYGB on Alpha- and Beta Cell Function and Sensitivity to Incretins in Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type2 Diabetes
Obesity, Morbid
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2021-03-04
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Prospective evaluation of gastric bypass patients, who will be examined before, 1 week and 3 months after the gastric bypass operation.
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of the study is to investigate the effect of Roux-en-Y gastric bypass (RYGB) on pancreatic alpha and beta-cell function and for the sensitivity of incretin hormones in patients with pre-operative type 2 diabetes.

Primary hypotheses:

* After RYGB, the sensitivity to GLP-1 and GIP is improved (improved insulinotropic effect).
* After RYGB, the insulin secretion improves during an oral glucose tolerance test within 3 months postoperatively.
* After RYGB, the insulin secretion during intraveneous stimulation with glucose or non-glucose (arginin) is unchanged.

Detailed description: Design: 12 patients with type 2 diabetes will be recruited.

All subjects will undergo 11 study visits: four visits before, three visits at 1 week after surgery and four visits at 3 months postoperatively:

* Oral glucose tolerance tests (OGTTs) with measurement of GLP-1 and GIP secretion will be performed before and 3 months post-surgery.
* Hyperglycemic clamps with co-infusion of saline, GLP-1 or GIP will be performed in a randomised order at three separate study visits in randomized order before, 1 week and 3 months after surgery.

Eligibility criteria: Inclusion Criteria:

* Inclusion criteria for RYGB in Denmark (ie. BMI \> 35 in the presence of obesity related co-morbidities as type 2 diabetes)
* Type 2 diabetes
* Pre-operative: Fasting plasma glucose ≥7,0 mmol/L or 2 hour plasma glucose ≥ 11,1 mmol/L (after pausing antidiabetic medication for a minimum of 3 days)
* Written informed consent.

Exclusion Criteria:

* Exclusion criteria for RYGB (psychiatric illness, obesity triggered by medical treatment for psychiatric illness, mental retardation, alcohol or drug abuse, severe heart-lung disease despite optimal medical treatment, previous serious problems with universal anesthesia, previous peritonitis, large hiatus hernia, diseases of the ventricle / previously complicated upper abdominal surgery, recurrent esophagitis, poor compliance).
* Type 2 diabetes where antidiabetic medication cannot be paused for 3 days.
* Pregnancy and breast-feeding.
* Hemoglobin \<7.0 mmol/L

Primary outcomes:
measure: Insulinotropic effects of GLP-1 and GIP
timeFrame: Change from before to 1 week and 3 months after RYGB
measure: Insulin secretion during oral stimulation
timeFrame: Change from before to 3 month after RYGB
measure: Insulin secretion during iv stimulation
timeFrame: Change from before to 1 week and 3 months after RYGB
Secondary outcomes:
measure: Alpha cell function
timeFrame: Change from before to after 1 week and 3 months after RYGB
Other outcomes:
Locations:
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital
Study officials:
References: