Secretory Unit Of Islet Transplant Objects Index Research Articles

Improved outcomes of islet autotransplant after total pancreatectomy by combined blockade of IL-1β and TNFα.

The efficacy of islet transplant is compromised by a significant loss of islet mass posttransplant due to an innate inflammatory reaction. We report the use of a combination of etanercept and anakinra (ANA+ETA) to block inflammatory islet damage in 100 patients undergoing total pancreatectomy with islet autotransplant. The patients were divided into 3 groups: no treatment (control [CTL]), etanercept alone (ETA), or a combination of etanercept and anakinra (ANA+ETA). Peritransplant serum samples were analyzed for protein markers of islet damage and for inflammatory cytokines. Graft function was assessed by fasting blood glucose, basal C-peptide, secretory unit of islet transplant objects (SUITO) index, and hemoglobin A1c . Administration of both antiinflammatory drugs was well tolerated without any major adverse events. Reductions in interleukin-6, interleukin-8, and monocyte chemoattractant protein 1 were observed in patients receiving ANA+ETA compared with the CTL group, while also showing a modest improvement in islet function as assessed by basal C-peptide, glucose, hemoglobin A1c , and SUITO index but without differences in insulin dose. These results suggest that double cytokine blockade (ANA+ETA) reduces peritransplant islet damage due to nonspecific inflammation and may represent a promising strategy to improve islet engraftment, leading to better transplant outcomes.

SUITO Index for Evaluation of Clinical Islet Transplantation

The major endpoints for clinical islet transplantation for type 1 diabetes are insulin independence and reduction of hypoglycemic episodes. Both endpoints are influenced by patients' and physicians' preferences regarding the use of exogenous insulin. Therefore, development of an objective endpoint for assessing clinical islet transplantation is desirable. HOMA-beta score is useful in assessing functional β-cell mass. However, this score uses blood insulin levels that are influenced by exogenous insulin injection and therefore is not suitable for patients who receive exogenous insulin. For assessing functional β-cell mass for type 1 diabetic patients after islet transplantation, we created the Secretory Unit of Islet Transplant Objects (SUITO) index using fasting C-peptide and fasting glucose. The formula of the SUITO index is fasting C-peptide (ng/ml)/[fasting blood glucose − 63 (mg/dl)] × 1500. We demonstrated that, within 1 month of islet transplantation, an average SUITO index of >26 was an excellent predictor of achieving insulin independence. In addition, daily SUITO index scores correlated with a reduction of insulin dose and adversely correlated with blood glucose levels during an intravenous glucose tolerance test. Other important endpoints, reduction of hypoglycemic episodes and quality of life, also correlated with the SUITO index. Thus, the SUITO index is excellent for assessing important endpoints (insulin independence, reduction of hypoglycemia, improved quality of life) after allogeneic islet transplantation.

Secretory Unit of Islet Transplant Objects (SUITO) Index Can Predict Severity of Hypoglycemic Episodes in Clinical Islet Cell Transplantation

One endpoint of clinical islet cell transplantation for type 1 diabetic patients is the elimination or reduction of hypoglycemia. We previously developed a simple tool to evaluate islet graft function: the secretory unit of islet transplant objects (SUITO) index. The aim of this study is to clarify the association between the SUITO index and hypoglycemic episodes. Data from 310 clinical evaluations of 11 islet recipients were included in this study. Fasting plasma C-peptide and glucose levels were measured at every evaluation. The SUITO index was calculated according to the following formula: 1500 × C-peptide level (ng/ml)/[blood glucose level (mg/dl) - 63]. The number of hypoglycemic events (<3.8 mmol/L) and severe hypoglycemic events (<2.2 mmol/L or hypoglycemic unawareness) was assessed on the basis of interviews and self-monitoring of blood glucose (SMBG). Receiver operating characteristic (ROC) analysis was performed to determine the cut-off values of the SUITO index for hypoglycemic events. Based on the ROC study, follow-up data after transplantations were divided into the following three groups: low-SUITO (SUITO index <10, n = 91), middle-SUITO (10 ≤SUITO index <26, n = 83), high-SUITO (SUITO index ≤26, n = 125). The frequency of total hypoglycemia in the high-SUITO group was significantly decreased when compared to the other groups (value with Kruskal-Wallis test p < 0.001). The frequency of total severe hypoglycemia was significantly decreased in the low-SUITO group compared to pretransplant status and further decreased in the middle- and high-SUITO group. Spearman correlation coefficients were -0.663 (p < 0.001) between the number of total hypoglycemic events per one month and the SUITO index and -0.521 (p < 0.001) between that of severe events and the SUITO index. The SUITO index could predict the severity of hypoglycemic episodes in type 1 diabetic patients who received islet cell transplantations.

Usefulness of the Secretory Unit of Islet Transplant Objects (SUITO) Index for Evaluation of Clinical Autologous Islet Transplantation

Background Assessing the engrafted islet mass is important in evaluating the efficacy of islet transplantation. We previously demonstrated that the average secretory unit of islet transplant objects (SUITO) index within 1 month of allogeneic islet transplantation was an excellent predictor of insulin independence. However, the usefulness of the SUITO index for evaluating autologous islet transplantation has not been explored. The purpose of the present study was to assess the relationship between the SUITO index and clinical outcomes after total pancreatectomy followed by autologous islet transplantation. Methods We performed 27 total pancreatectomies followed by autologous islet transplantation from October 2006 to January 2011. Cases were divided into an insulin-independent group (IIG; n = 12) and an insulin-dependent group (lDG; n = 15). The SUITO index was calculated by the formula [fasting C-peptide (ng/mL)/fasting glucose (mg/dL) −63] × 1,500. The average SUITO index within the first month of transplantation except for days 0, 1, and 2, maximum SUITO index, and most recent SUITO index were calculated in each case, and values were compared between the IIG and the IDG. Results The average SUITO index within 1 month was significantly higher in the IIG than in the IDG (24.6 ± 3.4 vs 14.9 ± 2.0, respectively; P < .02). The maximum SUITO indices were 45.7 ± 7.7 in the IIG and 30.1 ± 8.1 in the IDG (not significant), and the recent SUITO indices were 36.9 ± 6.7 in the IIG and 22.8 ± 6.1 in the IDG (not significant). Conclusions The average SUITO index within 1 month was an excellent predictor of insulin independence after total pancreatectomy followed by autologous islet transplantation.

Association Between the Secretory Unit of Islet Transplant Objects Index and Satisfaction With Insulin Therapy Among Insulin-Dependent Islet Recipients

Introduction When patients do not become insulin independent after islet cell transplantation (ICT), another aim is to eliminate severe hypoglycemia. Previously we reported that a secretory unit of islet transplant objects (SUITO) index score >10 was associated with a reduction of severe hypoglycemia. In this study, we assessed patients' satisfaction with their insulin therapy based on the SUITO index. Methods The study involved 11 islet recipients with type 1 diabetes who underwent ICT but still used insulin. From those patients, 41 Insulin Therapy Satisfaction Questionnaires (ITSQ) were collected. The SUITO index (fasting C-peptide [ng/mL] × 1500/blood glucose [mg/dL] − 63) was calculated at the same outpatient visits that the survey was administered. ITSQ scores were summarized using subscales and compared among 3 groups: the pre-ICT group, the low-SUITO group (SUITO index score <10 post-ICT), and the high-SUITO group (SUITO index score ≥10). Higher survey scores indicated better satisfaction. Results Significant trend relationships across the 3 groups were observed in the ITSQ total score ( P = .02 with Jonckheere-Terpstra test) and subscale scores of glycemic control ( P < .001), hypoglycemic control ( P = .01), and inconvenience of regimen ( P = .004). The pairwise comparisons between the 3 groups found significant differences: high SUITO versus both pre-ICT and low SUITO for the total ITSQ score ( P = .03 and .005, respectively) and glycemic control score ( P = .008 and .001, respectively), and high SUITO versus low SUITO for hypoglycemic control score ( P = .04) and inconvenience of regimen score ( P = .008). Conclusion Islet recipients with a SUITO index ≥10 experienced higher satisfaction with insulin injection therapy compared with the pre-ICT group, even though they were insulin dependent. A SUITO index ≥10 is a reasonable benchmark for successful ICT.

Super-High-Dose Islet Transplantation Is Associated With High SUITO Index and Prolonged Insulin Independence: A Case Report

Introduction One of the current issues of clinical islet transplantation is the difficulty to achieve a prolonged insulin-free status. Functional islet mass gradually decreased after transplantation. We developed the SUITO index, which reflects engrafted islet mass. The SUITO (Secretory Unit of Islet Transplant Objects) index more than 26.0 is associated with an insulin-free status. In this study, we have experienced that super-high-dose islet transplantation maintained insulin-free status and a high SUITO index for a prolonged period. Materials and methods Two islet isolations were performed in February 2007 and January 2008. Ductal injections were performed at the procurement site using the ET-Kyoto solution and pancreata preserved by a two-layer method. Islets were isolated using the modified Ricordi method. Both isolated islets were transplanted into a type 1 diabetic patient. Efficacy of islet transplantation was assessed by the amount of insulin requirements and SUITO index. Results Islet yields were 514,467 islet equivalents (IE) and 872,174 IE, with purities of 49% and 85% for the first and second islet transplantations, respectively. The patient received a total of 24,327 IE/kg body weight. The immunosuppression was based on the Edmonton protocol. After the second islet transplantation, the average SUITO index for the following 1 month was 48.5, and the patient became insulin-free. At postoperative day 1006, the SUITO index was 44.6 and the patient maintained an insulin-free status with excellent glycemic control. Conclusion Super-high-dose islet transplantation was associated with an high SUITO index and prolonged insulin independence.

Secretory Unit of Islet Transplant Objects (SUITO) Index Can Predict Outcome of Intravenous Glucose Tolerance Test

Background Simple monitoring of engrafted islet function is important for follow-up of recipients after islet transplantation. We previously developed a simple assessment tool for islet graft function; the secretory unit of islet transplant objects (SUITO) index. The aim of this study was to clarify the relationship between the SUITO index and the outcomes of intravenous glucose tolerance tests (IVGTT). Methods Fifteen series of blood samples from 6 islet recipients were collected before 3, 5, 10, 20, and 30 minutes after injection of 0.5 g/kg 50% dextrose. The SUITO index was calculated using plasma C-peptide and glucose level at fasting baseline. Samples were divided into the following 3 groups; low-SUITO (SUITO index <10; n = 3); middle-SUITO (SUITO index ≥10 to <26; n = 4); and high-SUITO (SUITO index ≥26; n = 8). Results A threshold SUITO index of 26 showed good sensitivity (85.7%) and specificity (75.0%) to predict a blood glucose level of >10 mmol/L at 30 minutes. Blood glucose levels in the low-SUITO group were significantly higher than among the other 2 groups at baseline and 10, 20 and 30 minutes ( P < .05). Glucose-level areas under the receiver-operating characteristic curve during IVGTT in the low-SUITO group were also significantly larger than among the other 2 groups ( P < .05). Conclusion The SUITO index, using only a fasting blood sample, predicted IVGTT outcomes.

ET-Kyoto Ductal Injection and Density-Adjusted Purification Combined With Potent Anti-Inflammatory Strategy Facilitated Single-Donor Islet Transplantation: Case Reports

Background The necessity to use multiple donors for achieving insulin independence in clinical islet transplantation is still a major issue. We have developed a modified islet isolation method for non–heart-beating donors (Kyoto method) to significantly increase islet yield. In this study, we further modified the method for brain-dead donors and in addition, introduced a potent anti-inflammatory strategy aiming for single-donor islet transplantation. Materials and methods Two islet isolations used pancreatic ductal preservation with the modified Kyoto solution and a density-adjusted purification method. Anti-interleukin-1-beta antibody (Anakinra) and anti-tumor necrosis factor-alpha (Eternacept) were administered during and after transplantation. The efficacy of the islet transplantation was assessed by the insulin requirement and SUITO (Secretory Unit of Islet Transplant Objects) index, wherein a value of more than 26.0 seems to be associated with insulin independence. Results Both isolated islet preparations met the criteria for transplantation. They were transplanted into two type 1 diabetic patients, both of whom became insulin independent with stable glycemic control. The average SUITO index within 1 month was 29.2 and 45.3. Conclusion The islet isolation method combined with a potent anti-inflammation strategy made it possible to achieve single-donor islet transplantation achieving a high SUITO index.

Excellence of S uito Index for Assessing Clinical Outcome of Islet Transplantation

Background Monitoring functional islet mass after transplantation is critical to follow patients. Previously we demonstrated that the average secretory unit of islet transplant objects (SUITO) index within 1 month was an excellent predictor of insulin-free status or reduction in insulin dose. In this study, we analyzed the usefulness of daily SUITO index to assess clinical outcomes. Methods Five patients underwent islet transplantation, including 3 who received 2 transplantations and 2 who received a single graft. All 5 patients achieved insulin-free status with 3 remaining insulin free at the time of evaluation. We analyzed the daily relative insulin dose and SUITO index. The daily relative insulin dose was calculated as the total daily insulin dose/average pretransplant insulin dose. The SUITO index was calculated as [fasting C-peptide (ng/mL)]/[fasting blood glucose (mg/mL) − 63] × 1,500. The data analyzed based on time after islet transplantation were categorized as within or after 1 month. Results Within 1 month after islet transplantation, there was no correlation between the daily relative insulin dose and the daily SUITO index ( P = .068; R = −0.33). After 1 month, the daily relative insulin dose and the daily SUITO index were strongly correlated ( P < .0001; R = −0.70). When the cutoff value of the SUITO index was decided at 26 for insulin-free status, the positive predictive value was 84.1% and negative predictive value 89.4%. Conclusion SUITO index was an excellent index to assess clinical outcomes beyond 1 month after islet transplantation.

SUITO Index for Evaluation of Efficacy of Single Donor Islet Transplantation

Evaluation of engrafted islets mass is important for clinical care of patients after islet transplantation. Recently, we developed the secretory unit of islet transplant objects (SUITO) index, which reflected engrafted islet mass. In this study, we evaluated the SUITO index for the prediction of clinical outcome after single islet transplantation. Single islet transplantations were performed into six type 1 diabetic patients. Isolated islets were quantitatively assessed at the time of transplantation. The SUITO index was calculated as follows: fasting C-peptide (ng/dl)/[fasting blood glucose (mg/dl) - 63] x 1500. Islet yield/recipient's body weight and SUITO index were evaluated, along with HbA(1C), relative insulin dose (insulin dose posttransplant/pretransplant), and M-values. HbA(1C) improved in all cases, irrespective of the SUITO index score or islet yield/body weight. The average SUITO index from postoperative days 3 to 30 (R(2) = 0.728, p < 0.04), but not islet yield/body weight (R(2) = 0.259, p = 0.303), correlated with relative insulin dose. The daily SUITO index strongly correlated with the daily relative insulin dose (R(2) = 0.558, p < 0.0001) and weakly correlated with the daily M-values (R(2) = 0.207, p < 0.02). A SUITO index score of less than 10 was associated with increasing insulin dose even after islet transplantation. The SUITO index seems to be a better predictor of success of islet transplantations than islet yield/body weight. SUITO index is recommended to assess clinical outcome of islet transplantation.

Evaluation of Engraftment After Single Islet Transplantation From a Brain-Dead Donor by the Secretory Unit of Islet Transplant Objects (SUITO) Index

Background Evaluation of engraftment is important to assess the success of islet transplantation. Recently, we developed a simple index of islet engraftment, the secretory unit of islet transplant objects (SUITO) index. The formula is: 1500 × fasting C-peptide level [ng/dL]/(fasting blood glucose levels [mg/dL]-63). A SUITO index of more than 26 was associated with insulin independence. Materials and Methods In this study, we compared islet engraftment efficacy using the SUITO index after a single infusion of islets from brain-dead donors into 6 recipients. We calculated the SUITO index from postoperative days 3 to 30. We compared the insulin reduction rate with the SUITO index and islet equivalent per kilogram body weight (IE/Kg). We also measured the level of glycosylated hemoglobin (HbA 1C) at 3 months posttransplantation to assess glycemic control after islet transplantation. Results In 5 cases, islets were cultured before transplantation and in 1 case they were transplanted without culture. Without culture, the SUITO index and insulin reduction rate were highest. The SUITO index significantly correlated with the insulin reduction rate ( P = .031, R 2 = .728), but the IE/kg was not significantly correlated ( P = .303) with the rate of insulin reduction. All cases showed improved HbA 1C to the normal range. Conclusions Immediate transplantation without culture substantially improved the efficacy of engraftment of transplanted islets. The SUITO index was a better predictor than islet mass per body weight for clinical outcomes.

Simple Evaluation of Engraftment by Secretory Unit of Islet Transplant Objects for Living Donor and Cadaveric Donor Fresh or Cultured Islet Transplantation

Background Evaluation of engraftment is important to assess the success of islet transplantation. Recently we developed secretory unit of islet transplant objects (SUITO) index for simple evaluation of engraftment. Assuming that normal subjects aged <40 years have 100% pancreatic beta-cell function, SUITO index was calculated by the formula: 1500 × fasting C-peptide immunoreactivity [ng/dL]/(fasting blood glucose [mg/dL] − 63). In this study, we compared the efficacy of islet transplantation from cadaveric and living donors using the SUITO index. Methods We performed eight islet transplantations with non–heart-beating donors (NHBDs) into five patients. Two patients received fresh islets once, one patient received fresh islets twice, one patient received cultured islets once, and one patient received cultured islets twice plus fresh islets once. In addition, one patient received fresh islets from a living donor. We calculated the SUITO index from postoperative days 3 to 30 for each case. Results Mean SUITO index after one fresh islet transplant was 11.7 ± 1.0, after two fresh islet transplants was 28.5 ± 3.4, after one cultured islet transplant was 2.1 ± 0.4, after two cultured islet transplant was 12.1 ± 1.9, and after two cultured islet transplant plus one fresh islet transplant was 26.7 ± 1.7. The mean SUITO index after single living donor islet transplant was 40.7 ± 2.6, which was significantly higher compared with all other groups. Insulin independence was obtained when the SUITO index was >26, which might reflect that 26% beta-cell mass was required for insulin independence. Conclusion SUITO index is useful to evaluate islet engraftment and to predict the possibility of insulin independence.