Diabetologia (1996) 39:462-468 Diabetologia 9 Springer-Verlag1996 Determinants of a normal (versus impaired) oral glucose tolerance after combined pancreas-kidney transplantation in IDDM patients F. Pfeffer 1, M.A. Nauck 2, S. Benz 3, A. Gwodzinski 3, R. Zink 3, M. Biising 4, H.-D. Becker ~, U.T. Hopt 1 i Department of Surgery,University of Rostock, Rostock, Germany 2Department of Medicine, Ruhr-University, Knappschaftskrankenhaus,Bochum, Germany 3Department of Surgery,Eberhard-Karls-University, Tttbingen,Germany 4Department of Surgery,Ruhr-University, Knappschaftskrankenhaus,Bochum, Germany Summary After successful pancreas transplantation, insulin-dependent diabetic patients are characterized by a normal or at worst impaired oral glucose toler- ance (World Health Organisation criteria). It is not known which pathophysiological mechanisms cause the difference between normal and impaired oral glu- cose tolerance. Therefore, we studied 41 patients af- ter successful combined pancreas-kidney transplanta- tion using stimulation in the fasting state with oral glucose (75 g), intravenous glucose (0.33 g/kg) and glucagon bolus injection (1 mg i. v.). Glucose (glucose oxidase), insulin and C-peptide (immunoassay) were measured. Repeated-measures analysis of vari- ance and multiple regression analysis were used to analyse the results which showed: 28 patients had a normal, and 13 patients had an impaired oral glucose tolerance. Impaired oral glucose tolerance was asso- ciated with a greatly reduced early phase insulin secretory response (insulin p <0.0001; C-peptide p =0.037). Age (p=0.65), body mass index (p = 0.94), immunosuppressive therapy (cyclosporin A p = 0.84; predniso(lo)ne p = 0.91; azathioprine p = 0.60) and additional clinical parameters were not different. Reduced insulin secretory responses in pa- tients with impaired oral glucose tolerance were also found with intravenous glucose or glucagon stimula- tions. Exocrine secretion (a-amylase in 24-h urine collections) also demonstrated reduced pancreatic function in these patients (-46 %; p = 0.04). Multiple regression analysis showed a significant correlation of 120-rain glucose with ischaemia time (p = 0.003) and the number of HLA-DR mismatches (p=0.026), but not with HLA-AB-mismatches (p -- 0.084). In conclusion, the pathophysiological ba- sis of impaired oral glucose tolerance after pancreas transplantation is a reduced insulin secretory capac- ity. Transplant damage is most likely caused by peri- operative influences (ischaemia) and by the extent of rejection damage related, for example, to DR-mis- matches. [Diabetologia (1996) 39: 462-468] Keywords Pancreas transplantation, insulin secre- tion, pancreatic hormones, oral glucose tolerance, glucagon stimulation Received: 22 June 1995 and in revised form: 18 October 1995 Corresponding author: Dr. M.A. Nauck, Department of Inter- nal Medicine, Ruhr-University,Knappschaftskrankenhaus, In der Schornau 23-25, D-44892 Bochum-Langendreer, Ger- many Abbreviations: BMI, Body mass index; HLA, human leucocyte antigen; IGT, impaired oral glucose tolerance; NGT, normal oral glucosetolerance; RM-ANOVA,repeated measures anal- ysis of variance; WHO, World Health Organisation; ]DDM, in- sulin-dependent diabetes mellitus. Pancreas transplantation is a reasonable therapeutic option for patients with insulin-dependent diabetes (IDDM) of long duration, who require a kidney graft because of end-stage nephropathy making dialysis treatment necessary [1-5]. A widely used surgical technique with good functional results is the trans- plantation of a whole pancreas with exocrine drain- age into the recipients' urinary bladder and venous anastomosis to the systemic circulation [6, 7]. After successful transplantation, day-long plasma glucose concentrations are close to normal [4, 5], as also indi- cated by normal glycated haemoglobin values [4, 5, 8]. Although success is usually defined as non-