Glucose Control in Pancreas Transplantation Assessed by 72-hr Continuous Glucose Monitoring

Once euglycemia has been achieved after pancreas transplantation (PTX), the recurrence of chronic hyperglycemia is challenging. The identification of the subjects at risk for returning to the diabetic state because of graft loss or any other cause is difficult and often delayed. Consequently, early appropriate treatment is usually not feasible. Available biochemical parameters and imaging tools still lack the diagnostic accuracy to detect early failure of the transplanted pancreas (1–6). This study aimed to compare glucose profiles in patients with type 1 diabetes treated with simultaneous pancreas/kidney transplantation (SPK) or pancreas transplantation alone (PTA) with those under intensive insulin therapy (IIT) and with healthy controls (HCs) by means of continuous glucose monitoring system (CGMS) and to assess CGMS effectiveness as a predictor of graft dysfunction (GD) thereafter. Thirty-nine subjects were submitted to CGMS: 11 SPK patients, 10 PTA patients, 8 IIT patients, and 10 HCs. All participants were instructed to maintain their normal daily activities, diet, exercise, and medications. All transplanted patients showed normal oral glucose tolerance test and were in stable tacrolimus-based immunosuppressive regimen, at least 4 months after transplantation and without any previous report of rejection episodes. Mean glucose concentration (MGC) for 72 hr and variability (absolute value of mean glucose [mg/dL]−100) (7) were compared among groups. After 5 years, baseline data were reassessed comparing patients who had shown GD with those without GD. Continuous variables were compared between groups using analysis of variance for repeated measures or Kruskal-Wallis test, as appropriate, and followed by Tukey and Nemenyi post hoc tests, respectively. Comparisons between the SPK and PTA groups and between groups with and without diabetes were performed using the unpaired t test. Categorical variables were analyzed using chi-square test or Fisher exact test, according to sample size. P<0.05 was taken as significant for all comparisons. Table 1 displays the main characteristics of the study groups. The IIT group showed significantly higher glycated hemoglobin levels than both transplanted groups. The PTA group showed higher tacrolimus levels than the SPK group, and they were on more frequent use of prednisone. MGC and variability were higher in the IIT group than in all other groups. The PTA and SPK groups showed higher MGC than the HCs. Comparisons between transplanted groups revealed higher MGC in the PTA group than in the SPK group (P<0.05 for all comparisons previously mentioned).TABLE 1: Baseline characteristics of the studied groupsDuring the follow-up period after CGMS (mean [SD], 58.8 [3.7] months), 5 of the 10 PTA patients completed the study with functioning allograft and absence of diabetes, whereas GD and diabetes were confirmed in the other 5 patients after a mean follow-up of 22.0 (18.4) months. In the SPK group, one patient lost follow-up and was excluded from the prospective analysis, and another patient presented with persistent hyperglycemia and GD 8 months after the use of the CGMS. The other nine SPK patients remained with functioning transplants and absence of diabetes. Transplanted patients who were evaluated as having diabetes (6/21) presented with chronic graft rejection revealed by pancreas biopsy in all cases. Interestingly, patients with diabetes after PTX had shown higher MGC measured by CGMS 5 years before when compared with those who remained with functioning allograft (107.1 [22.3] vs. 96.6 [16.5] mg/dL; P<0.01). Importantly, MGC at CGMS greater than 104 mg/dL was the best discriminatory level between individuals who lost the pancreatic graft thereafter and those who remained euglycemic after 5 years. There were no differences between these groups regarding other initial parameters of glucose metabolism (fasting glucose, 2-hr glucose after overload, glycated hemoglobin, C peptide, or insulin). Our data confirm the efficacy of PTX (SPK and PTA) in achieving better glucose control when compared with IIT. To our knowledge, this is the first study to compare patients having undergone PTA to those having undergone SPK and healthy subjects by the CGMS system. The results of the present study strengthen the potential use of the CGMS as a valuable tool for evaluating subjects in the post-PTX period after normalizing oral glucose tolerance test. This sensitive method for the analysis of glucose profiles revealed differences between transplanted patients and HCs. Moreover, a better glucose control as evaluated by CGMS was achieved in SPK when compared with PTA. Such differences may be attributed to several causes, such as the effect of immunosuppressive drugs or subclinical graft failure. However, long-term follow-up revealed that individuals with lower MGC assessed by CGMS showed the best chances of remaining diabetes free after PTX. These new data may prove helpful in evaluating candidates for preemptive pancreas biopsy for the early detection of chronic GD, especially among patients having undergone PTA, similar to that suggested in islet transplantation studies (8, 9). Márcio W. Lauria 1,2 José Maria Figueiró2 Marcelo D. Sanches1 Ricardo C. Gontijo2 Bernardo A. Mariano1 Ângela Maria Q. Lana1 Antônio Ribeiro-Oliveira1 1Laboratory of Endocrinology Department of Internal Medicine Federal University of Minas Gerais Belo Horizonte Minas Gerais, Brazil 2Transplantation Unit Felicio Rocho Hospital Belo Horizonte Minas Gerais, Brazil