Obesity, Morbid, Type2 Diabetes
Conditions
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.
Interventions
DIAGNOSTIC_TESTOral Glucose Tolerance Test
Standard test of glucose tolerance with ingestion of 75 g glucose followed by blood sampling.
DIAGNOSTIC_TESTHyperglycemic clamp with infusion of saline, GLP-1 or GIP
Blood glucose kept at 15 mmol/L via iv 20% glucose infusions. Primed co-infusion of either: * Saline * GLP-1 (Prime dose 6 pmol/kg, infusion 1 pmol/kg/min) * GIP (Prime dose 3 pmol/kg, infusion 1.5 pmol/kg/min).
Sponsors
University of Copenhagen
Hvidovre University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
Prospective evaluation of gastric bypass patients, who will be examined before, 1 week and 3 months after the gastric bypass operation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulinotropic effects of GLP-1 and GIP | 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 | Change from before to 3 month after RYGB | AUC of C-peptide during oral glucose tolerance test |
| Insulin secretion during iv stimulation | 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
| Measure | Time frame | Description |
|---|---|---|
| Alpha cell function | Change from before to after 1 week and 3 months after RYGB | Glucagon secretion during hyperglycemic clamps |
Countries
Denmark
Outcome results
None listed