Pancreatic and islet autotransplantation

The techniques of segmental pancreatic autotransplantation and intraportal islet autografting have been reported to prevent diabetes after resection of the diseased pancreas. Unless total pancreatectomy is done, transplant function cannot be assessed without measuring insulin in the venous effluent. Islet infusion appears to be a more uncertain technique than segmental autotransplantation, probably because of technical difficulties in obtaining sufficient islets. Both methods have serious potential for morbidity and mortality, which must be balanced against the possible benefits of improved glucose homeostasis. In segmental autografts we recommend an intraperitoneal transplant site with iliac vessel anastomosis, and a lateral pancreaticojejunostomy to provide ductal drainage. For islet transplantation we recommend extreme caution and the use of only very pure islet preparations for portal vein infusions. There is insufficient long-term follow-up of patients with successful auto- or allotransplants to be certain that secondary complications of diabetes will be less than those of patients on insulin therapy. Further experience is necessary before the long-term functional survival of segmental or islet autografts will be known.     

Deterioration of glycemic control after corticosteroid administration in islet autotransplant recipients: a cautionary tale

Islet autotransplantation (IAT) is performed at the time of total pancreatectomy (TP) to prevent or minimize post-surgical diabetes. Corticosteroids induce insulin resistance and present a risk to islet autografts, through glucotoxicity and increased metabolic demand on a marginal islet mass. We present four IAT recipients treated with oral or injected corticosteroids after transplant for medical conditions unrelated to chronic pancreatitis or TPIAT. Hyperglycemia or insulin resistance was evident in all four patients, including reversion to long-term insulin therapy in two patients. One patient receiving corticosteroid injections had a transient increase in hemoglobin A1c (+0.6% above baseline), and one patient given a one time dose of oral dexamethasone exhibited hyperglycemia despite high insulin (>200 mU/L) and C-peptide (15.3 ng/mL) production on an oral glucose tolerance test. IAT recipients have insufficient islet mass to compensate for the insulin resistance induced by corticosteroids. Caution should be given to using these agents in IAT recipients. When corticosteroids are medically necessary, insulin therapy should be administered temporarily to compensate for the increased metabolic demand and minimize long-term risks on the islet graft.     

Institutional indications for islet transplantation after total pancreatectomy

Background/Purpose

This study was designed to establish institutional indications for pancreatic islet transplantation by examining patients with total pancreatectomy as candidates for islet allotransplantation.

Methods

In 12 patients who underwent total pancreatectomy, we compared pre-and postoperative plasma glucose level, body mass index, HbA1c, and daily insulin use; we examined candidacy for islet allotransplantation based on the guidelines of Japan’s islet transplantation registry.

Results

Eight of the 12 patients with total pancreatectomy were operated for intraductal papillary mucinous neoplasm. At our institution, the 5-year survival of patients with intraductal papillary mucinous neoplasm was far better (76.3%) than that of patients with pancreatic cancer. Postoperatively, plasma glucose level, HbA1c, and daily insulin use were increased in all patients with total pancreatectomy. Of the 12 patients treated with total pancreatectomy, 4 (intraductal papillary mucinous neoplasm, n = 2; islet cell tumor, n = 1; and acute pancreatitis due to arteriovenous malformation, n = 1) showed deteriorated diabetic control and therefore were considered to be candidates for islet allotransplantation according to the guidelines.

Conclusions

Islet allotransplantation could be indicated for patients with favorable postoperative survival who have had a total pancreatectomy for either benign or neoplastic disease.     

Pancreas and islet transplantation

Clinical islet allotransplantation has been a safe, but largely unsuccessful enterprise. It has been difficult to apply techniques that might overcome the islet yield and allograft rejection problems encountered in animal experiments. Over the past decade only 4 of 74 attempts at islet transplantation have been followed by long term withdrawal of exogenous insulin therapy, and there are problems with intrepretation of the outcome in each of theses cases, as discussed in the preceding section. In the islet allograft situation, the failures may have been for technical or for immunological reasons. In the autograft situation, rejection could not occur and the failures were clearly technical. The success rate with islet autografts gives some indication as to what might be achieved with islet allotransplantation if rejection could be prevented in the latter situation. The islet autotransplant experience is not entirely predictative, however, for two reasons: 1) the uncertainty over the contribution of the pancreatic remnant to carbohydrate metabolism when less than the total pancreatectomy is done; 2) the increased difficulty with liberating islets from diseased, fibrotic pancreases. For both islet allo- and autotransplantation, the success rate will probably remain low until more effective techniques are developed for preparation of islets from adult pancreases. For the allograft situation, additional advances will be needed in immunosuppression or in techniques to alter islet graft immunogenicity in order to overcome the rejection phenomenon.     

Imaging prediction of islet yield and post-operative insulin requirement in children undergoing total pancreatectomy with islet autotransplantation

BackgroundPredicting post-operative glycemic control in children undergoing total pancreatectomy with islet autotransplantation (TPIAT) remains difficult. The purpose of our study was to explore preoperative imaging as a marker for islet yield and insulin need in pediatric patients undergoing TPIAT.MethodsThis was a retrospective study of children (≤18 years) who had undergone TPIAT between April 2015 and December 2018 and had 6 or more months of post-TPIAT follow-up. Patient specific factors (height, weight, body mass index [BMI], body surface area [BSA]) and pancreas volume segmented from the most recent pre-operative cross-sectional imaging were explored as predictors of islet yield (total islet counts [TIC], total islet equivalents [TIE], islet equivalents per kilogram body weight [IEQ/kg]) and glycemic control (total daily dose of insulin per kilogram body weight [TDD/kg], insulin independence) using Pearson correlation and univariate and multiple regression.ResultsThirty-three patients, median age 13 years (IQR: 10–15 years), 64% female (21/33) met inclusion criteria. Nine patients (27%) achieved insulin independence at six months. Median TIE isolated was 310,000 (IQR: 200,000–460,000). Segmented pancreas volume was moderately associated with TIE (coefficient estimate = 0.34, p = 0.034). On multiple regression analysis, there was no significant predictor of insulin independence but number of attacks of pancreatitis (estimate = 0.024; p = 0.018) and segmented pancreas volume by body weight (estimate = ?0.71; p < 0.001) were significant predictors of insulin TDD/kg.ConclusionPancreas volume segmented from pre-TPIAT imaging has predictive performance for post-TPIAT insulin need in children.     

Autotransplantation of culture-positive islet product: is dirty always bad?

Background

In selected patients, total pancreatectomy with islet autotransplantation (TPIAT) effectively relieves pain caused by chronic pancreatitis and ameliorates the brittle diabetes of the apancreatic state. Patients often undergo multiple endoscopic and surgical interventions prior to TPIAT, increasing the risk for pancreas colonization with enteric microorganisms. Little is known of the safety of transplanting islet cells with microbial contamination.

Methods

A prospectively collected database of 80 patients submitted to TPIAT at the Medical University of South Carolina from March 2009 to February 2012 was retrospectively reviewed. Patient charts were reviewed for postoperative infectious complications and organisms identified were compared with those identified in pre-transplant islet cultures.

Results

A total of 35 patients (43.8%) had a positive pre-transplant islet cell Gram stain or islet cell culture from the final islet preparation solution. Of these 35 patients, 33 (94.3%) were given antibiotics prophylactically post-transplant for a positive islet Gram stain or culture. Twenty patients (57.1%) receiving Gram stain- or culture-positive islets developed postoperative infectious complications, but only four patients (11.4%) developed infections that concorded with their pre-transplant islet product.

Conclusions

Islet transplant solutions are frequently culture-positive, presumably as a result of prior pancreas intervention. Microbial contamination of islet preparations should not preclude autotransplantation.     

Successful long-term exocrine and endocrine function of the autotransplanted pancreas in humans

Segmental pancreatic autotransplantation has been performed to prevent the severe metabolic complications of total pancreatectomy. To date 15 segmental pancreatic autotransplants have been reported, 11 of which have been performed for relief of the abdominal pain of chronic pancreatitis. The major problem with segmental pancreatic graft relates to the handling of the pancreatic duct and its secretion. In all the reported cases, the autotransplanted duct was either ligated, stapled, or occluded with synthetic polymers. In this article we present a patient who has undergone a total pancreatectomy with segmental pancreatic autotransplantation and subsequent Roux-en-Y anastomosis to the transplanted duct. Physiologic studies indicate normal endocrine function 7 years following transplant. The patient is insulin-independent and tolerates a normal meal, requiring no oral pancreatic enzyme supplementation. To our knowledge this is the first long-term report of a patient with an autotransplanted pancreas who is presently both insulin sufficient and with intact exocrine function.     

The prognostic significance of glutamic acid decarboxylase antibodies in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation

AimIslet autotransplantation (IAT) is considered a ‘non-immune’ model of islet transplant, with no risk for autoimmune-mediated beta cell loss, but we have previously observed de novo type 1 diabetes in one total pancreatectomy with islet autotransplantation (TPIAT) recipient. We aimed to investigate the clinical significance of glutamic acid decarboxylase antibodies (GADA), as a sensitive marker for autoimmune diabetes mellitus (DM), in patients with chronic pancreatitis undergoing TPIAT.MethodsWe identified 9 patients undergoing TPIAT with elevated GADA pre-TPIAT (8 non-diabetic and 1 with C-peptide positive DM), otherwise demographically similar to GADA negative TPIAT recipients (n = 341). Metabolic and clinical measures related to islet cell function were recorded both before and after TPIAT.ResultsNone of the 9 TPIAT patients achieved insulin independence after surgery, vs. 33% of GADA negative patients (n = 318 with 1-yr follow-up). The two patients with the highest titters of GADA (> 250 IU/mL) both experienced islet graft failure, despite normoglycaemia pre-TPIAT and high islet mass transplanted (5276 and 9378 IEQ per kg), with elevated HbA1c levels post-TPIAT (8.3%, 9.6%). The remaining 7 seven were insulin dependent with partial graft function and HbA1c levels < 7%.ConclusionInsulin dependence was more frequent in 9 patients with elevated GADA prior to TPIAT than in GADA negative TPIAT recipients, with graft failure in 2 cases. We speculate that beta-cell autoimmunity may occur in a small subset of TPIAT recipients and that beta cell antibody testing prior to TPIAT may be warranted to identify individuals at higher risk for insulin dependence.     

Pediatric Islet Autotransplantation: Indication,Technique, and Outcome

Chronic pancreatitis is a rare disease in childhood. However, when severe, a total pancreatectomy may be the only option to relieve pain and restore quality of life. An islet autotransplant performed at the time of pancreatectomy can prevent or minimize the postsurgical diabetes that would otherwise result from pancreatectomy alone. In this procedure, the resected pancreas is mechanically disrupted and enzymatically digested to separate the islets from the surrounding exocrine tissue, and the isolated islets are infused into the portal vein and engraft in the liver. Because patients are receiving their own tissue, no immunosuppression is required. Islet autotransplant is successful in two thirds of children—these patients are insulin independent or require little insulin to maintain euglycemia. Factors associated with a more successful outcome include a younger age at transplant (<13 years), more islets transplanted, and lack of prior surgical procedures on the pancreas (partial pancreatectomy or surgical drainage procedures).     

Improved vascular engraftment and function of autotransplanted pancreatic islets as a result of partial pancreatectomy in the mouse and rat

Aims/hypothesis The few patients subjected to autotransplantation of pancreatic islets after pancreatectomy usually become normoglycaemic after using islets from the resected organ only, whereas allogeneic recipients usually require at least two grafts to retain normoglycaemia. Previous experimental studies have demonstrated that islets transplanted to non-pancreatectomised recipients acquire a markedly decreased blood vessel density, which leads to a hypoxic microenvironment. The aim of the present study was to test the hypothesis that autotransplanted islets have better vascular engraftment and function as a result of the pancreatic surgery involved. Materials and methods In the present study, athymic mice and inbred rats were subjected to a 60% pancreatectomy and transplanted with human or rat islets, respectively, 4 days later. Control animals underwent sham surgery. Blood flow, oxygen tension, vascular density and endocrine volume in the islet grafts were measured 1 month after transplantation. Separate grafts were used for perfusion experiments and for assessment of beta cell proliferation and endocrine cellular apoptosis at different time periods after transplantation. Results Islet grafts in partially pancreatectomised recipients had an increased blood flow, oxygen tension, blood vessel density and endocrine mass 1 month post-transplantation compared with control animals. They also exhibited increased insulin release in perfusion experiments performed 1 month post-transplantation, and decreased cellular apoptosis early after transplantation. Conclusions/interpretation The present study shows that the pancreatectomy procedure itself has beneficial effects on the engraftment of transplanted human and rat islets. Our results provide an additional explanation, besides diminished immunological responses, of the much better outcome of islet autotransplantations compared with allogeneic transplantations in the clinic.     

No islets left behind: islet autotransplantation for surgery-induced diabetes

For patients with severe chronic pancreatitis refractory to medical interventions, total pancreatectomy can be considered to relieve the root cause of pain. The goal of a simultaneous islet autotransplant is to prevent or minimize the otherwise inevitable surgical diabetes. Islet autotransplant can successfully preserve some endogenous islet function in the majority of recipients, which mediates protection against brittle diabetes. Most maintain reasonably good glycemic control, while 30 %-40 % successfully discontinue insulin therapy. With islet autotransplants reaching a wider clinical audience, refinements in islet isolation techniques and strategies to protect islet grafts post-transplant may further improve the success of this procedure.     

Promotion of beta-cell regeneration by betacellulin in ninety percent-pancreatectomized rats.

Betacellulin is thought to promote growth and differentiation of pancreatic beta-cells. We investigated the effect of betacellulin on regeneration of pancreatic beta-cells in 90%-pancreatectomized rats. Ninety percent pancreatectomy was performed in male Wistar rats and betacellulin (0.5 microg/g body weight) or saline was administered daily for 10 d starting immediately after pancreatectomy. In pancreatectomized rats, the morning-fed plasma glucose was significantly lower and the plasma insulin concentration was significantly higher in betacellulin-treated rats than those in control rats for up to 4 wk. Thirty days after pancreatectomy, a glucose tolerance test was performed. Betacellulin reduced the plasma glucose response to ip glucose loading. In control rats, the plasma insulin concentration was significantly lower and did not respond to glucose. In contrast, the plasma insulin concentration increased slightly but significantly in betacellulin-treated rats. Thirty days after pancreatectomy, the beta-cell mass was greater and the insulin content was significantly higher in betacellulin-treated rats than those in control rats. The numbers of islet cell-like cluster and bromodeoxy uridine/insulin double- positive cells in both islet cell-like cluster and islets were significantly higher in betacellulin-treated rats. These results indicate that administration of betacellulin improves glucose metabolism by promoting beta-cell regeneration in 90%-pancreatectomized rats.     

Effect of total gastrectomy on remnant islet cell function after major pancreatectomy in rats.

This study was designed to investigate the effect of total gastrectomy on remnant islet cell function after 85% distal pancreatectomy in rats. Eight-week-old Wistar male rats were divided into the following three groups: group 1, laparotomy; group 2, distal pancreatectomy; and group 3, distal pancreatectomy with total gastrectomy. Four weeks after the operation, i.v. glucose tolerance tests (ivGTT) were performed. The body weight in group 3 rats 4 weeks after the operation was significantly lower than that of the other two groups (p less than 0.05). Glucose tolerance was impaired in both groups 2 and 3; group 3 was more impaired than group 2. Immunoreactive insulin (IRI) concentration in both groups 2 and 3 was much lower than that in group 1 throughout the ivGTT. Furthermore, IRI concentration in group 3 was lower than group 2 at all times. The integrated secretion of insulin for the 45 minutes after glucose injection was lower in group 3 than in group 2. It is concluded that total gastrectomy injures remnant pancreatic endocrine function after 85% distal pancreatectomy in rats.     

Segmental pancreatic autotransplantation for chronic pancreatitis. A preliminary report

A patient who underwent 95% pancreatectomy with autotransplantation of the body and tail of the gland to the femoral area for chronic pancreatitis is presented. The pain resolved, and the patient's blood glucose level remained within normal limits. High levels of insulin were found in the iliac vein on the transplanted side. Patency of the graft was demonstrated by technetium scan and arteriography and followed by a color-coded Doppler imaging system. Segmental pancreatic autotransplantation offers a method of relieving pain with preservation of endocrine function in selected patients with chronic pancreatitis.     

Continuous Glucose Monitoring Analysis as Predictor of Islet Yield and Insulin Requirements in Autologous Islet Transplantation After Complete Pancreatectomy

We analyzed the pretransplant continuous glucose monitoring (CGM) data of 45 patients that underwent total pancreatectomy followed by autologous islet transplantation (AIT) at the University of Arizona Medical Center. Traditional and novel metrics of CGM time series were correlated to the total islet count (TIC), islet equivalents (IEQs), and weight-normalized IEQs (IEQ/kg). In a subset cohort (n = 26) we analyzed the relationship among the infused number of islets, the CGM indicators, and the first recorded insulin requirement after the procedure. We conclude that receiving a high islet yield is sufficient yet not necessary to achieve low or null insulin requirements within the first 50 days after surgery. Furthermore, CGM inertia and CGM length of curve (2 novel CGM indicators) are shown to be correlated to islet yield, and the CGMs normalized area (Ao) and time ratio above hyperglycemic level (To) are strongly correlated to insulin requirement. A screening test based on To is shown to have 100% sensitivity and 88% specificity discriminating insulin independence upon discharge.     

Severely fibrotic pancreases from young patients with chronic pancreatitis: evidence for a ductal origin of islet neogenesis

While it is known that islet cell mass increases considerably after birth, general uncertainty surrounds the source of new beta cells in humans. Chronic pancreatitis (CP) presents a natural injury model for studying postnatal beta-cell regeneration in the human pancreas. In this report, we present histological evidence from human CP pancreases to support the theory that islet neogenesis can occur from ductal precursor cells after birth. Three young patients (ages 16, 12, and 28 years) underwent total pancreatectomy for the management of CP followed by islet isolation and autologous transplantation to prevent or minimize postsurgical diabetes. In all cases, the pancreases had extensive fibrosis, a rock-like consistency, and calcifications in the ducts. During islet isolations, we observed the unusual release of islets with many ductal fragments. In histopathological evaluation of these pancreases, solid cords of cells sometimes formed islet like structures intraductally or extending from ductal structures. Immunofluorescence staining for chromogranin, insulin, proinsulin, PDX1, glucagon, and cytokeratins confirmed these structures to be composed of chromogranin-positive endocrine cells which included both β-cells and α-cells. Labeling for Ki67 to demonstrate mitotic activity showed frequent labeling of duct epithelial cells and of some periductal cells. Using insulin and wide-spectrum cytokeratin double immunofluorescent labeling, we found insulin-positive cells to be present within the ductal lumens, among the cytokeratin-positive ductal epithelium, and extending from the ductal epithelium into surrounding connective tissues, providing evidence for a ductal origin of islet neogenesis.     

Lack of compensatory increase in islet blood flow and islet mass in GK rats following 60% partial pancreatectomy

The effects of a 60% partial pancreatectomy were studied in hyperglycemic GK (Goto-Kakizaki) rats. Partial pancreatectomy or a sham operation was performed on 12-week-old female Wistar rats, GK rats or hybrids between male GK rats and female Wistar rats. Measurements of pancreatic blood flow and islet blood flow were performed by a microsphere technique 2 weeks after surgery. Glucose tolerance was decreased in hybrid compared with Wistar rats, and in GK rats compared with both hybrid and Wistar rats before surgery. Partial pancreatectomy induced minor changes in glucose tolerance. Wistar rats had a decreased islet mass following partial pancreatectomy. Both hybrid and GK rats showed a significant decrease in relative islet volume, but only GK rats in total islet mass, compared with Wistar rats 2 weeks after surgery. Pancreatic blood flow and islet blood flow did not significantly differ between sham-operated Wistar, hybrid or GK rats. After partial pancreatectomy, islet blood flow in relation to islet mass increased 3-fold in Wistar rats and 2-fold in hybrid rats. In contrast, GK rats showed no increase in islet blood flow following partial pancreatectomy. It is concluded that compensatory mechanisms after partial pancreatectomy are operating less efficiently in hybrid and GK rats.     

Peripheral insulin release after pancreatic resection: the effect of decreased beta-cell mass with systemic or portal drainage

Surgical alteration of the pancreas can result in several anatomic alterations which may affect insulin release. We evaluated the effects of resection, systemic drainage, and autotransplantation of the canine pancreas on peripheral insulin levels and glucose disposal as measured by iv glucose tolerance tests (IVGTT) and a steady state hyperglycemic challenge (clamp). Proximal pancreatectomy (PPx) with reduced beta-cell mass and intact portal drainage resulted in a modestly elevated fasting glucose level and increased integrated glucose response to IVGTT. Compared to preoperative normals, basal insulin was unchanged from preoperative controls; however, peak insulin and integrated insulin response to IVGTT were decreased in PPx animals. Splenocaval drainage or autotransplantation of the distal pancreas resulted in normalization of the severely altered insulin response and fasting glucose levels. K values were significantly reduced after all three procedures. Clamp studies confirmed the basal glucose and insulin findings of the IVGTT. During the clamp, PPx animals had peripheral insulin values approximately 50% of normal controls, while autotransplantation and splenocaval drainage animals had insulin values that approximate normal controls. All three postsurgical groups had blunted insulin levels during stable hyperglycemia. Glucose utilization rates were severely decreased in all three groups. Reduction of beta-cell mass with intact portal drainage resulted in reduced insulin response to glucose challenge by either IVGTT or clamp. Systemic drainage of this same reduced beta-cell mass resulted in peripheral insulin levels comparable to normal controls. Denervation (autotransplantation) had little additive effect. All three groups demonstrated severely decreased rates of glucose disappearance as measured by both IVGTT and clamp studies. Therefore, reduction in beta-cell mass, drained systemically or portally, results in altered glucose disposal regardless of the peripheral insulin levels.     

Effect of partial pancreatectomy on diabetic status in BALB/c mice.

Pancreatic regeneration after pancreatectomy has been well documented in animal models. However, the phenomenon of pancreatic regeneration in diabetes has not been exploited as yet. We report here the restoration of euglycaemic status in streptozotocin (STZ)-induced diabetic BALB/c mice, after 50% pancreatectomy. We observed that, after pancreatectomy, STZ-diabetic mice showed a rapid improvement in glycaemic status, starting from the 8th postoperative day, and remained normoglycaemic throughout a 90-day follow-up study. STZ-induced diabetic and control non-diabetic BALB/c mice underwent pancreatectomy and were monitored regularly for changes in body weight, plasma glucose and serum insulin concentrations and histological status of the pancreas. All the pancreatectomised animals showed euglycaemic status from about 20 days after operation, whereas a majority (around 70%) of the diabetic, sham-operated animals died of sustained hyperglycaemia by 20-30 days after operation. Examination of the regenerating pancreas indicated nesidioblastotic activity and supported the theory of a ductal origin of islet stem cells. Islets isolated from the regenerating pancreas showed a progressive increase in islet area (1227.9+/-173.2 micrometer(2) on day 5 compared with 2473.8+/-242.0 micrometer(2) by day 20). The increment in insulin concentrations and subsequent decrement in glycaemia of the diabetic pancreatectomised animals indicate islet neogenesis occurring after the operative insult, leading to a normoglycaemic status, probably recapitulating ontogeny. We have shown that induction of a regenerative stimulus (pancreatectomy) in conditions of STZ-induced diabetes may trigger pancreatic regenerative processes, thereby restoring a functional pancreas, in STZ-diabetic mice.     

Glycemic Outcomes of Islet Autotransplantation

Purpose of Review

While there has been a growing utilization of total pancreatectomy with islet autotransplantation (TPIAT) for patients with medically refractory chronic pancreatitis over the past few decades, there remains a lack of consensus clinical guidelines to inform the counseling and management of patients undergoing TPIAT. In this article, we review the current clinical practice and published experience of several TPIAT centers, outline key aspects in managing patients undergoing TPIAT, and discuss the glycemic outcomes of this procedure.

Recent Findings

Aiming for lower inpatient glucose targets immediately after surgery (usually 100–120 mg/dl), maintaining all patients on subcutaneous insulin for at least 3 months to “rest” islets before an attempt is made to wean insulin, and close outpatient endocrinology follow-up after TPIAT particularly in the first year is common and related to better outcomes. Although TPIAT procedures and glycemic outcomes may differ across surgical centers, overall, approximately one third of patients are insulin independent at 1 year after TPIAT. Higher islet yield and lower preoperative glucose levels are among the strongest predictors of short-term post-operative insulin independence. Beyond 1 year post-operatively, the clinical management and long-term glycemic outcomes of patients after TPIAT are more variable.

Summary

A multidisciplinary approach is essential in optimizing the preoperative, inpatient, and post-operative management and counseling of patients about the expected glycemic outcomes after surgery. Consensus guidelines for the clinical management of diabetes after TPIAT and harmonization of data collection protocols among TPIAT centers are needed to address the current knowledge gaps in clinical care and research and to optimize glycemic outcomes after TPIAT.