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

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

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.

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