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Effect of RYGB on Alpha- and Beta Cell Function and Sensitivity to Incretins in Patients With Type 2 Diabetes (BETASIN)

Primary Purpose

Type2 Diabetes, Obesity, Morbid

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Oral Glucose Tolerance Test
Hyperglycemic clamp with infusion of saline, GLP-1 or GIP
Sponsored by
Hvidovre University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type2 Diabetes

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hvidovre University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Oral glucose tolerance test

Hyperglycemic clamp with saline infusion combined with arginine test

Hyperglycemic clamp with GLP-1 infusion

Hyperglycemic clamp with GIP infusion

Arm Description

Oral glucose tolerance test with ingestion of 75 g glucose and blood sampling. This test will be performed before and 3 months after RYGB.

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.

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.

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.

Outcomes

Primary Outcome Measures

Insulinotropic effects of GLP-1 and GIP
Insulin secretion during steady state of all hyperglycemic clamps
Insulin secretion during oral stimulation
AUC of C-peptide during oral glucose tolerance test
Insulin secretion during iv stimulation
Insulin secretion during hyperglycemic clamp with saline infusion and during argininine iv stimulation test

Secondary Outcome Measures

Alpha cell function
Glucagon secretion during hyperglycemic clamps

Full Information

First Posted
February 26, 2021
Last Updated
March 14, 2022
Sponsor
Hvidovre University Hospital
Collaborators
University of Copenhagen
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1. Study Identification

Unique Protocol Identification Number
NCT04782999
Brief Title
Effect of RYGB on Alpha- and Beta Cell Function and Sensitivity to Incretins in Patients With Type 2 Diabetes
Acronym
BETASIN
Official Title
Effect of RYGB on Alpha- and Beta Cell Function and Sensitivity to Incretins in Patients With Type 2 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
January 2015 (Actual)
Primary Completion Date
January 2022 (Actual)
Study Completion Date
March 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hvidovre University Hospital
Collaborators
University of Copenhagen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type2 Diabetes, Obesity, Morbid

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Prospective evaluation of gastric bypass patients, who will be examined before, 1 week and 3 months after the gastric bypass operation.
Masking
Participant
Allocation
Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Oral glucose tolerance test
Arm Type
Active Comparator
Arm Description
Oral glucose tolerance test with ingestion of 75 g glucose and blood sampling. This test will be performed before and 3 months after RYGB.
Arm Title
Hyperglycemic clamp with saline infusion combined with arginine test
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Hyperglycemic clamp with GLP-1 infusion
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Hyperglycemic clamp with GIP infusion
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
Oral Glucose Tolerance Test
Intervention Description
Standard test of glucose tolerance with ingestion of 75 g glucose followed by blood sampling.
Intervention Type
Diagnostic Test
Intervention Name(s)
Hyperglycemic clamp with infusion of saline, GLP-1 or GIP
Intervention Description
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).
Primary Outcome Measure Information:
Title
Insulinotropic effects of GLP-1 and GIP
Description
Insulin secretion during steady state of all hyperglycemic clamps
Time Frame
Change from before to 1 week and 3 months after RYGB
Title
Insulin secretion during oral stimulation
Description
AUC of C-peptide during oral glucose tolerance test
Time Frame
Change from before to 3 month after RYGB
Title
Insulin secretion during iv stimulation
Description
Insulin secretion during hyperglycemic clamp with saline infusion and during argininine iv stimulation test
Time Frame
Change from before to 1 week and 3 months after RYGB
Secondary Outcome Measure Information:
Title
Alpha cell function
Description
Glucagon secretion during hyperglycemic clamps
Time Frame
Change from before to after 1 week and 3 months after RYGB

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Hvidovre University Hospital
City
Hvidovre
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Effect of RYGB on Alpha- and Beta Cell Function and Sensitivity to Incretins in Patients With Type 2 Diabetes

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