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

NCT04782999 | Completed DMC

• 1 other identifier: H-7-2014-010
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Type2 Diabetes; Obesity, Morbid

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Alpha cell function

  Change from before to after 1 week and 3 months after RYGB

Study Arms (4)

Oral glucose tolerance test

ACTIVE COMPARATOR

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

Hyperglycemic clamp with saline infusion combined with arginine test

ACTIVE COMPARATOR

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

Hyperglycemic clamp with GLP-1 infusion

ACTIVE COMPARATOR

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

Hyperglycemic clamp with GIP infusion

ACTIVE COMPARATOR

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

Interventions

Oral Glucose Tolerance Test DIAGNOSTIC_TEST

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

Oral glucose tolerance test

Hyperglycemic clamp with infusion of saline, GLP-1 or GIP 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 GLP-1 infusion; Hyperglycemic clamp with saline infusion combined with arginine test

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Hvidovre University Hospital: lead
• University of Copenhagen: collaborator

Study Sites (1)

Hvidovre University Hospital

Hvidovre, Denmark

Location

MeSH Terms

Conditions

Obesity, Morbid

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: Prospective evaluation of gastric bypass patients, who will be examined before, 1 week and 3 months after the gastric bypass operation.

Study Record Dates

• First Submitted: February 26, 2021
• First Posted: March 4, 2021
• Study Start: January 1, 2015
• Primary Completion: January 1, 2022
• Study Completion: March 1, 2022
• Last Updated: March 16, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)