Effect of RYGB on Alpha- and Beta Cell Function and Sensitivity to Incretins in Patients With Type 2 Diabetes
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Type2 Diabetes
- Sponsor
- Hvidovre University Hospital
- Enrollment
- 9
- Locations
- 1
- Primary Endpoint
- Insulinotropic effects of GLP-1 and GIP
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Investigators
Maria Saur Svane
MD, PhD
Hvidovre University Hospital
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
Outcomes
Primary Outcomes
Insulinotropic effects of GLP-1 and GIP
Time Frame: Change from before to 1 week and 3 months after RYGB
Insulin secretion during steady state of all hyperglycemic clamps
Insulin secretion during oral stimulation
Time Frame: Change from before to 3 month after RYGB
AUC of C-peptide during oral glucose tolerance test
Insulin secretion during iv stimulation
Time Frame: Change from before to 1 week and 3 months after RYGB
Insulin secretion during hyperglycemic clamp with saline infusion and during argininine iv stimulation test
Secondary Outcomes
- Alpha cell function(Change from before to after 1 week and 3 months after RYGB)