Preserved Insulin Sensitivity and Kidney Function One Year After Successful Pancreas Transplantation
Espen Nordheim1,2, Kåre Birkeland1,2, Anders Åsberg1,3, Anders Hartmann1,2, Trond Jenssen1,4.
1Department of Transplantation Medicine, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; 2Faculty of Medicine, University of Oslo, Oslo, Norway; 3School of Pharmacy, University of Oslo, Oslo, Norway; 4Metabolic and Renal Research Group, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Tromsø, Norway
Introduction: Pancreas transplantation (PTX) has become an established treatment for a selected group of patients with unstable type 1 diabetes mellitus. It may be performed as simultaneous pancreas and kidney transplantation (SPK) or as pancreas transplantation alone (PTA). Endured immunosuppressive therapy is prone to reduce insulin release, insulin sensitivity and kidney function over time. In this study, we aimed to investigate changes in these functions over the first year post-transplant in patients with surviving pancreas grafts.
Methods: We studied 67 patients that had undergone PTA (n=37) or SPK (n=30) with functioning grafts at one year after transplantation, and had repeated oral glucose tolerance testing (OGTT) and measured glomerular filtration rate (mGFR; iohexol clearance) at week 8 and 52 after transplantation. Glucose, insulin and c- peptide were sampled fasting and 120 minutes after glucose load. All patients were transplanted between September 2011 and November 2016 at our national transplant center. SPK and PTA patients received similar quadruple immunosuppressive therapy including ATG induction, tacrolimus (through levels of 10-12 tapered to 6-10 µg/L by 8 weeks) mycophenolate mofentil (2 g/day) and steroids (tapered to 10 mg/day by week 4 and 5 mg/day by week 26.
Results: From week 8 to 52 after transplantation the mean fasting blood glucose levels decreased significantly in both patient groups (SPK 5.4 to 5.1 mmol/L, PTA: 5.4 to 5.2 mmol/L; p<0.005). Mean 120-minute glucose levels were significantly higher in week 8 than in week 52 (SPK 6.5 vs 5.7 mmol/L, PTA: 5.4 vs 5.2mmol/L; p<0.005). Mean fasting insulin and 120-minute insulin levels were stable while fasting C- peptide levels were significantly reduced by week 52 (SPK: 1500 vs 1087 pmol/L, PTA: 1210 vs 1021pmol/L, p<0.005). mGFR did not change from week 8 to week 52 (SPK: 55 vs 59 ml/min/1.73m², PTA: 71 vs 72 ml/min/1.73m², p=0.24).
Conclusion: Glycaemia improved and fasting C-peptide concentrations were reduced one year after successful pancreas transplantation, indicating an improved insulin sensitivity. Kidney function was not negatively affected by the tacrolimus based immunosuppressive therapy over the first year.
