GLP-1 Effects on Insulin and Glucagon in PTDM

University of Oslo (UIO)

Status

Completed

Conditions

Post-transplant Diabetes Mellitus

Treatments

Dietary Supplement: Glucagon-like peptide-1 (GLP-1)

Other: Isotonic saline

Other: Hyperglycemic clamp

Study type

Interventional

Funder types

Other

Identifiers

NCT02591849

2014/666

Details and patient eligibility

About

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.

Enrollment

24 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

24 participants in 2 patient groups, including a placebo group

Glucagon-like peptide-1 (GLP-1)

Active Comparator group

Description:

Twelve eligible renal transplant recipients with PTDM and twelve age, gender, BMI and renal function-matched non-diabetic renal transplant recipients will be randomized to continuous unblinded intravenous infusion of GLP-1 with an infusion rate of 0.8 pmol/kg/min or isotonic saline (placebo) on two experimental days performed 2-4 weeks apart. The GLP-1 infusion will consist of 42.5 nmol/mL GLP-1 (7-36) amide, 12.5 mL 5% human albumin and isotonic saline added to a total volume of 50 mL. After 60 min, a 2 hour hyperglycemic clamp will be initiated, where plasma glucose will be elevated by 5 mmol/L from each individual fasting plasma glucose in both groups. This will be done to measure concentrations of glucagon and insulin in hyperglycemic conditions.

Treatment:

Other: Hyperglycemic clamp

Dietary Supplement: Glucagon-like peptide-1 (GLP-1)

Isotonic saline

Placebo Comparator group

Description:

The included patients will receive concomitant intravenous infusion of isotonic saline on one of the two experimental days

Treatment:

Other: Hyperglycemic clamp

Other: Isotonic saline