Post-transplant Diabetes Mellitus
Conditions
Brief summary
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.
Interventions
Sponsors
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of glucagon during fasting glycemia and during hyperglycemic conditions measured in picomoles per liter | 4 weeks | The primary objective of the present study is to measure fasting plasma glucagon concentration and the suppression of glucagon during hyperglycemia (hyperglycemic clamp) measured in picomoles per liter with and without concomitant iv infusion of glucagon-like peptide-1 (GLP-1) in renal transplant recipients with and without PTDM |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose-potentiated arginine test | 4 weeks | Investigate the functional reserve capacity in glucagon and insulin release (measurement of functional α-cell and β-cell mass) by a glucose-potentiated arginine test; since arginine is a glucose-independent stimulator of the release of both hormones. |
| Insulin sensitivity index | 4 weeks | Estimate insulin sensitivity index (ISI) by recording the glucose infusion rate during the hyperglycemic clamp, corrected for the prevailing plasma insulin concentrations. |
Countries
Norway
Outcome results
None listed