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

Hvidovre University Hospital9 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Type2 Diabetes Obesity, Morbid

Interventions

Oral Glucose Tolerance TestDIAGNOSTIC_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 GIPDIAGNOSTIC_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).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Insulinotropic effects of GLP-1 and GIP

Insulin secretion during steady state of all hyperglycemic clamps

Time frame: 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

Time frame: 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

Time frame: Change from before to 1 week and 3 months after RYGB

Secondary Outcomes

Alpha cell function

Glucagon secretion during hyperglycemic clamps

Time frame: Change from before to after 1 week and 3 months after RYGB