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

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.

Study Overview

• Status: Completed
• Conditions: Obesity, Morbid; Type2 Diabetes
• Intervention / Treatment: Diagnostic test: Oral Glucose Tolerance Test; Diagnostic test: Hyperglycemic clamp with infusion of saline, GLP-1 or GIP

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark
    • Hvidovre University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulinotropic effects of GLP-1 and GIP	Insulin secretion during steady state of all hyperglycemic clamps	Change from before to 1 week and 3 months after RYGB
Insulin secretion during oral stimulation	AUC of C-peptide during oral glucose tolerance test	Change from before to 3 month after RYGB
Insulin secretion during iv stimulation	Insulin secretion during hyperglycemic clamp with saline infusion and during argininine iv stimulation test	Change from before to 1 week and 3 months after RYGB

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alpha cell function	Glucagon secretion during hyperglycemic clamps	Change from before to after 1 week and 3 months after RYGB

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Collaborators: University of Copenhagen

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2015
• Primary Completion (ACTUAL): January 1, 2022
• Study Completion (ACTUAL): March 1, 2022

Study Registration Dates

• First Submitted: February 26, 2021
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (ACTUAL): March 4, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Diabetes Mellitus; Diabetes Mellitus, Type 2; Obesity, Morbid
• Other Study ID Numbers: H-7-2014-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No