GLP-1 Effects on Insulin and Glucagon in PTDM

GLP-1 Restores Altered Insulin and Glucagon Secretion in Post-transplantation Diabetes Mellitus

Post-transplantation diabetes mellitus (PTDM) develops in 10-15 % of all renal transplant recipients within 10 weeks after transplantation, and has been associated with increased risk of cardiovascular disease and impaired patient survival. PTDM is primarily believed to be a variant of type 2 diabetes mellitus (T2DM), but the pathophysiology underlying the impaired glucose metabolism in renal transplant recipients with PTDM is unclear and some aspects are still poorly investigated. Hyperglycemic clamp investigations with concomitant infusion of glucagon-like peptide-1 (GLP-1) are warranted for a thorough characterization of the α-cell and β-cell function.

The primary objective of the present study is to investigate whether hyperglucagonemia is present in renal transplant recipients with PTDM. Furthermore, the investigators aim to examine the insulinotropic and glucagon suppressive effects of GLP-1 (compared to placebo) in PTDM patients during fasting glycemia and during hyperglycemic conditions (hyperglycemic clamp), respectively.

Inclusion Criteria:

• Renal transplant recipients more than 1 year post transplant with stable renal function (less than 20% deviation in serum creatinine within the last 2 months) and stable prednisolone dose (maximum 5 mg/day) the last three months before inclusion
• Diagnose of PTDM on standard clinical follow-up performed 8 weeks and 1 year post transplant at OUS-Rikshospitalet (fasting plasma glucose ≥ 7.0 mmol/l and/or 2-hour plasma glucose ≥ 11.1 mmol/l following an oral glucose tolerance test) OR
• Non-diabetic renal transplant recipients with a normal glucose tolerance test (control group)
• > 18 years of age
• BMI 18.5-29.9 kg/m2
• Signed informed consent

Exclusion Criteria:

• Severe liver disease
• Pancreatitis (chronic or acute), previous bowel resection, inflammatory bowel disease, malignancy (previous or actual)
• Estimated GFR < 25 ml/min/1.73 m2
• Pregnant or nursing mothers