BETASIN: Effect of RYGB on Alpha- and Beta Cell Function and Sensitivity to Incretins in Patients With Type 2 Diabetes
Study Details
Study Description
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:
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After RYGB, the sensitivity to GLP-1 and GIP is improved (improved insulinotropic effect).
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After RYGB, the insulin secretion improves during an oral glucose tolerance test within 3 months postoperatively.
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After RYGB, the insulin secretion during intraveneous stimulation with glucose or non-glucose (arginin) is unchanged.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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:
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Oral glucose tolerance tests (OGTTs) with measurement of GLP-1 and GIP secretion will be performed before and 3 months post-surgery.
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Oral glucose tolerance test Oral glucose tolerance test with ingestion of 75 g glucose and blood sampling. This test will be performed before and 3 months after RYGB. |
Diagnostic Test: Oral Glucose Tolerance Test
Standard test of glucose tolerance with ingestion of 75 g glucose followed by blood sampling.
|
| Active Comparator: Hyperglycemic clamp with saline infusion combined with arginine test Hyperglycemic clamp with blood glucose kept at 15 mmol/L by adjustable infusions of intraveneous glucose for 120 min with co-infusion of saline. After 120 min an arginine test with infusion of 50 g Arginine is performed. This test will be performed before, 1 week and 3 months after RYGB. |
Diagnostic Test: Hyperglycemic 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).
|
| Active Comparator: Hyperglycemic clamp with GLP-1 infusion Hyperglycemic clamp with blood glucose kept at 15 mmol/L by adjustable infusion of intraveneous glucose for 90 min with co-infusion of GLP-1. This test will be performed before, 1 week and 3 months after RYGB. |
Diagnostic Test: Hyperglycemic 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).
|
| Active Comparator: Hyperglycemic clamp with GIP infusion Hyperglycemic clamp with blood glucose kept at 15 mmol/L by adjustable infusions of intraveneous glucose for 90 minutes with co-infusion of GIP. This test will be performed before, 1 week and 3 months after RYGB. |
Diagnostic Test: Hyperglycemic 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).
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Alpha cell function [Change from before to after 1 week and 3 months after RYGB]
Glucagon secretion during hyperglycemic clamps
Eligibility Criteria
Criteria
Inclusion Criteria:
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Inclusion criteria for RYGB in Denmark (ie. BMI > 35 in the presence of obesity related co-morbidities as type 2 diabetes)
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Type 2 diabetes
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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)
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Written informed consent.
Exclusion Criteria:
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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).
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Type 2 diabetes where antidiabetic medication cannot be paused for 3 days.
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Pregnancy and breast-feeding.
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Hemoglobin <7.0 mmol/L
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hvidovre University Hospital | Hvidovre | Denmark |
Sponsors and Collaborators
- Hvidovre University Hospital
- University of Copenhagen
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H-7-2014-010