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

NCT ID: NCT04782999

Last Updated: 2022-03-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2022-03-31

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.

Conditions

Type2 Diabetes; Obesity, Morbid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Oral Glucose Tolerance Test

Intervention Type: DIAGNOSTIC_TEST

Standard test of glucose tolerance with ingestion of 75 g glucose followed by blood sampling.

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.

Group Type: ACTIVE_COMPARATOR

Hyperglycemic clamp with infusion of saline, GLP-1 or GIP

Intervention Type: DIAGNOSTIC_TEST

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).

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.

Group Type: ACTIVE_COMPARATOR

Hyperglycemic clamp with infusion of saline, GLP-1 or GIP

Intervention Type: DIAGNOSTIC_TEST

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).

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.

Group Type: ACTIVE_COMPARATOR

Hyperglycemic clamp with infusion of saline, GLP-1 or GIP

Intervention Type: DIAGNOSTIC_TEST

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).

Interventions

Oral Glucose Tolerance Test

Standard test of glucose tolerance with ingestion of 75 g glucose followed by blood sampling.

Intervention Type: 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).

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• 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

• Type 2 diabetes where antidiabetic medication cannot be paused for 3 days.
• Pregnancy and breast-feeding.
• Hemoglobin <7.0 mmol/L

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Copenhagen

OTHER

Sponsor Role: collaborator

Hvidovre University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Maria Saur Svane

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hvidovre University Hospital

Hvidovre, , Denmark

Countries

Denmark

Other Identifiers

H-7-2014-010

Identifier Type: -

Identifier Source: org_study_id