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We evaluated whether 1,5-anhydroglucitol (1,5-AG) (GlycoMark(®)), a test for measuring postprandial glucose and glucose variability, could be a tool for assessing short-term glycemic control in islet cell transplant (ICT) subjects. Data of 21 subjects, with type 1 DM and allogenic islet transplantation, who had concomitant fructosamine, HbA1c, 1,5-AG (n = 85 samples), and capillary glucose self-monitoring measurements (n = 2,979) were analyzed retrospectively at different time points after ICT. A significant negative association was observed between 1,5-AG and HbA1c (p = 0.02), but not with fructosamine. When HbA1c was divided in quartiles as <5.6, 5.6-5.9, 5.9-6.2, and >6.2, a decrease of an estimated 0.70 ± 0.30 µg/ml in 1,5-AG was associated with each quartile of increase in HbA1c (p < 0.0001). There was a significant decline of 1.64 ± 0.3mg/dl in postprandial glucose values for each 1 unit increase in 1,5-AG (p < 0.0001). For those with HbA1c ≥ 6.0% when 1,5-AG was ≥8.15 µg/ml, the mean estimated glucose level was 103.71 ± 3.66 mg/dl, whereas it was 132.12 ± 3.71 mg/dl when 1,5-AG was <8.15 µg/ml. The glucose variability (Glumax - Glumin) in subjects with 1,5-AG <8.15 µg/ml was 46.23 mg/dl greater than the subjects with 1,5-AG ≥8.15 µg/ml (HbA1c ≥ 6.0%). There was no significant association between GlycoMark and glucose variability where HbA1c < 6%. 1,5-AG significantly associated with postprandial glucose levels and glucose variability in ICT recipients with near-normal HbA1c (6.0-6.5%) levels. These findings suggest that 1,5-AG can be used to differentiate those ICT subjects with higher glucose variability despite having near-normal HbA1c. However, prospective studies are needed to evaluate the association between GlycoMark levels and the parameters of graft dysfunction/failure.

Pancreatic islet allotransplantation is an option for patients with unstable type 1 diabetes mellitus (T1DM). Major improvements in islet isolation techniques and the implementation of steroid-free immunosuppressive regimens can maintain insulin independence in the majority of T1DM for at least 1 year after transplantation. Recent studies have emphasized the impact of sirolimus on female reproductive tract. In this communication we report on the alterations of the female reproductive tract in 18 chronically immunosuppressed patients with T1DM following allogenic islet transplantation. Previous research has shown development of ovarian cysts in islet transplant patients receiving sirolimus. We extensively reevaluated this and other possible side effects on the female reproductive system. These side effects have been underestimated, although they are significant, requiring surgical or intensive medical treatment. Pre- and posttransplant gynecological evaluation should be performed to address the development of complications secondary to sirolimus in order to intervene sooner with alternative therapies.

The initial success of islet transplantation (ITx) is followed by graft dysfunction (GDF) and insulin reintroduction. Exenatide, a GLP-1 agonist, increases insulin and decreases glucagon secretion and has potential for beta-cell regeneration. To improve functional islet mass, exenatide treatment was given to ITx recipients with GDF. The objective of this study was to assess metabolic and hormonal effects of exenatide in GDF. In this prospective, single-arm, nonrandomized study, 11 type 1 diabetes recipients of ITx with GDF had HbA1c, weight, insulin requirements, and 5-h mixed meal tolerance test (MMTT; with/without exenatide given before test) at baseline, 3, 6, and 12 months after initiating exenatide treatment. Baseline MMTT showed postprandial hyperglycemia and hyperglucagonemia. Daily exenatide treatment resulted in improved glucose, increased amylin/insulin ratio, and decreased proinsulin/insulin ratio as assessed by MMTT. Glucagon responses remained unchanged. Exenatide administration 1 h before MMTT showed decreased glucagon and glucose at 0 min and attenuation in their postprandial rise. Time-to-peak glucose was delayed, followed by insulin, proinsulin, amylin, and C-peptide, indicating glucose-driven insulin secretion. Five subjects completed 12-month follow-up. Glucose and glucagon suppression responses after MMTT with exenatide were no longer observed. Retrospective 3-month analysis of these subjects revealed higher and sustained glucagon levels that did not suppress as profoundly with exenatide administration, associated with higher glucose levels and increased C-peptide responses. In conclusion, Exenatide suppresses the abnormal postprandial hyperglucagonemia and hyperglycemia observed in GDF. Changes in amylin and proinsulin secretion may reflect more efficient insulin processing. Different degrees of responsiveness to exenatide were identified. These may help guide the clinical management of ITx recipients.

In order to make islet transplantation a therapeutic option for patients with diabetes there is an urgent need for more efficient islet cell processing to maximize islet recovery. Improved donor management, organ recovery techniques, implementation of more stringent donor criteria, and improved islet cell processing techniques may contribute to enhance organ utilization for transplantation. We have analyzed the effects of donor and islet processing factors on the success rate of human islet cell processing for transplantation performed at a single islet cell processing center. Islet isolation outcomes improved when vasopressors, and in particular pitressin, and steroids were used for the management of multiorgan donors. Higher islet yields were obtained from adult male donors, BMI >25 kg/m2, adequate glycemic control during hospital stay, and when the pancreas was retrieved by a local surgical team. Successful isolations were obtained in 58% of the cases when > or = 4 donor criteria were met, and even higher success rates (69%) were observed when considering > or = 5 criteria. Our data suggest that a sequential, integrated approach is highly desirable to improve the success rate of islet cell processing.