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

Obesity, Morbid Clinical Trial

— BETASIN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04782999
• Other study ID #: H-7-2014-010
• Status: Completed
• Phase: N/A
• Start date: January 2015
• Est. completion date: March 2022

Study information

• Verified date: March 2022
• Source: Hvidovre University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: March 2022
• Est. primary completion date: January 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Obesity, Morbid
• Type2 Diabetes

Intervention

Diagnostic Test:
• Oral Glucose Tolerance Test
Standard test of glucose tolerance with ingestion of 75 g glucose followed by blood sampling.
• 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).

Locations

Country	Name	City	State
Denmark	Hvidovre University Hospital	Hvidovre

Sponsors (2)

Lead Sponsor	Collaborator
Hvidovre University Hospital	University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Insulin secretion during oral stimulation	AUC of C-peptide during oral glucose tolerance test	Change from before to 3 month after RYGB
Primary	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	Alpha cell function	Glucagon secretion during hyperglycemic clamps	Change from before to after 1 week and 3 months after RYGB