Islet Autotransplantation Research Articles

P.11: Does race predict outcomes of total pancreatectomy with islet auto-transplantation?

P.11: Does race predict outcomes of total pancreatectomy with islet auto-transplantation?

Assessment of long-term graft function following total pancreatectomy and autologous islet transplantation: the Leicester experience.

Total pancreatectomy and islet autotransplantation (TPIAT) is a recognised treatment for chronic pancreatitis (CP) with the potential to mitigate or prevent pancreatogenic diabetes. We present our 10-year follow-up of TPIAT patients. The University Hospitals of Leicester performed 60 TPIAT procedures from September 1994 to May 2011. Seventeen patients completed their 10-year assessment and were grouped using the modified Auto-Igls criteria; good response, n=5 (insulin-independent for first 5 years post-TPIAT); partial response, n=6 (insulin requirements <20 iU/day post-TPIAT) and poor response, n=6 (insulin requirements ≥20 iU/day post-TPIAT). C-peptide, haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were undertaken preoperatively (baseline), then at 3, 6 months and then yearly for 10 years. Data was analysed using analysis of variance (ANOVA). Median C-peptide levels were significantly higher, 120 minutes following OGTT, in the "good response" compared to "partial" and "poor" groups (two-way ANOVA test, P<0.0001). All groups demonstrated preservation of C-peptide release. HbA1c levels were significantly lower in the "good response" compared to "partial" and "poor" groups (two-way ANOVA test, P<0.0003 and P<0.0001). Median fasting glucose levels at 30 and 120 min following OGTT, were significantly lower in the "good response" compared to "partial" and "poor" groups (two-way ANOVA test, P<0.0001 and P<0.0001). TPIAT preserves long-term islet graft functions in 10-year follow up. Even in patients in the poor response group, there is evidence of C-peptide release (>0.5 ng/mL) after OGTT stimulation potentially preventing long-term diabetes-related complications.

310.8: Naturally purified islets in total pancreatectomy (TP) and islet autotransplant (IAT) for chronic pancreatitis: a model to evaluate impact of exocrine co-transplant on graft function

310.8: Naturally purified islets in total pancreatectomy (TP) and islet autotransplant (IAT) for chronic pancreatitis: a model to evaluate impact of exocrine co-transplant on graft function

235.1: Dosing rC1 and rC2 collagenases based on percent parenchymal mass improves digestion efficacy of fibrotic chronic pancreatitis pancreases intended for pediatric islet auto-transplantation

235.1: Dosing rC1 and rC2 collagenases based on percent parenchymal mass improves digestion efficacy of fibrotic chronic pancreatitis pancreases intended for pediatric islet auto-transplantation

Advances in the Management of Pain in Chronic Pancreatitis.

The data on recent advances in managing chronic pancreatitis (CP) pain is limited. This review highlights the role of endotherapy and the advances in the overall management of pain in CP. Of late, pancreatic biodegradable stents have been used in endotherapy with appreciable success. These include slow, medium, and fast degrading stents, which optimize the overall management of CP and could prevent the need for multiple procedures. Endoscopic ultrasound-guided celiac plexus block is reserved in selected patients to treat debilitating pain. Total pancreatectomy with islet autotransplantation in small duct disease has shown promising results. The indications for treating pain in CP with endoscopy and surgery need to be better defined. The complexity of pain control due to the incomplete understanding of pathomorphology makes the management of CP challenging. The current treatment methods are still evolving. Therapy aims to reduce pain, optimize recovery, maintain quality of life, and meet postoperative needs. Initial management includes lifestyle modification, nutrition optimization, risk factor reduction with abstinence from alcohol, cessation of tobacco and smoking. Supportive medical management involves the judicial use of analgesics, neuromodulators, antioxidants, pancreatic enzyme replacement for insufficiency, and diabetes management. Patients with intractable pain are ideal for therapeutic intervention. Being less invasive with an acceptable complication rate makes endotherapy the preferred first-line treatment. If found to be cost-effective, biodegradable stents can reduce the overall cost. Unfortunately, if patients remain symptomatic, surgery is preferred in case of failure or recurrence. For optimal results, appropriate patient selection is vital to maximizing outcomes.

Improved Quality of Life Among Chronic Pancreatitis Patients Undergoing Total Pancreatectomy With Islet Autotransplantation-Single Center Experience With Large Cohort of Patients.

Total pancreatectomy with islet autotransplantation (TPIAT) is the treatment of choice to preserve pancreatic endocrine function, alleviate pain, and improve quality of life (QoL) when other strategies are ineffective for chronic pancreatitis (CP) patients. This study utilized pancreatic disease-specific surveys developed by the European Organisation for Research and Treatment of Cancer (EORTC) to conduct a comprehensive, single-center examination of a large cohort of patients to gain understanding of QoL post-TPIAT. Two validated QoL surveys of the EORTC-QLQ-C30 and QLQ-PAN26-were administered in a prospective cohort of CP patients during pre-and post-operative scheduled visits. A total of 116 patients responded to the preoperative survey and were included in this study. The global health scale of QLQ-C30 was significantly improved after TPIAT when compared to baseline with delta scores of 24.26, 20.54, and 26.7 at 1, 2, and 3years post-TPIAT (p < 0.001). The EORTC-PAN26 revealed significant improvements in symptom scales for pancreatic pain, bloating, digestive symptoms, taste, indigestion, weight loss, body image, and future worries. The comprehensive surveys in such a large cohort expands the QoL criterion in CP patients and indicates significant improvement in QoL post-TPIAT, further validating TPIAT as a treatment option for refractory CP.

Islet graft function by mixed meal tolerance testing is sustained over 4years in young children undergoing total pancreatectomy with islet autotransplantation.

Children with intractable chronic pancreatitis may require total pancreatectomy with islet autotransplantation (TPIAT) for pain relief. The IAT reduces the severity of post- pancreatectomy diabetes. We analyzed 635 mixed meal tolerance tests (MMTT) in 134 children undergoing TPIAT to determine whether superior survival of islet grafts explains higher rates of insulin independence previously reported in young children (n=52, age 3-11years) versus adolescents (n=82, age 12-18years). For MMTT, children consumed Boost HP and we sampled C-peptide and glucose repeatedly over 2h. The trajectory of outcomes before and after TPIAT was compared between children and adolescents using data from pre-TPIAT and 3, 6months, 1, 2, 3, and 4years post-TPIAT and mixed linear models with a random effect for child. Cox regression was used to analyze time outcomes (e.g., time to first off insulin). Islet mass transplanted, measured as islet equivalents (IEQ), was higher in adolescents (p=.003) but IEQ/kg was higher in young children (p<.001) because of their lower weight. AUC C-peptide in young children increased somewhat over 4years, but was stable in adolescents (p=.0013). AUC glucose increased more in adolescents over time post-TPIAT (p=.0024). Islet function by AUC C-peptide:AUC glucose ratio was better preserved in young children (p<.001). Adolescents were less likely to wean off insulin (hazard ratio .44 [95% CI .28, .69]). These data support an advantage of young age in islet graft survival after TPIAT. The greater likelihood of insulin independence in young children may be driven by better islet survival after transplant.

Total pancreatectomy with islet autotransplantation reduces opioid use and improves nutritional support in children with debilitating pancreatitis.

Chronic pancreatitis (CP) can result in opioid dependence and nutritional challenges in children. Total pancreatectomy with islet autotransplantation (TPIAT) is a viable surgical option in appropriately selected patients. We examined differences between children who met criteria for TPIAT versus those who did not and continued with non-operative management. Retrospective observational cohort study of patients evaluated for TPIAT between August 2014 and July 2020 was performed. Cohort-based analyses between TPIAT and non-TPIAT groups were performed. Analyses included 121 patients, 69 of whom underwent TPIAT. Demographics, genetic risk factors, and anatomic variants did not differ between groups. TPIAT patients were more likely to have CP (88% vs 71%; p = 0.02), had higher median number of endoscopic retrograde cholangiopancreatography procedures (2.0 vs 1.0; p = 0.0001), and had higher likelihood of opioid use (61% vs 42%; p = 0.04) and nutritional supplementation (23% vs 4%; p = 0.004), compared to non-TPIAT. At 6 months post-TPIAT, patients had lower use of any analgesic pain medications (39% vs 73%; p = 0.0002) and lower use of opioids (9% vs 39%; p = 0.0006), compared to non-TPIAT patients at 6 months after evaluation. At 6 months post-TPIAT, rate of exclusively oral nutrition increased from 77% to 86%, and total parenteral nutrition use decreased from 13% to 0% (p = 0.02). In children referred for TPIAT evaluation, there is greater burden of disease in those selected for operation, compared to patients who do not undergo operation. TPIAT achieves lower analgesic pain medication use compared to continuation with non-TPIAT management and achieves freedom from nutritional supplementation. Level of evidence: Retrospective comparative study, Level III.

Diffuse calcification of pancreas impairs endocrine function and predicts poor outcome in total pancreatectomy with islet autotransplantation

In patients with chronic pancreatitis, pancreatic calcification is a risk factor for diabetes development, poor islet yield, and metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT). We investigated whether calcification pattern based on computed tomography is associated with outcomes using our database of 200 consecutive TPIAT procedures. Three groups were compared: noncalcification (NC); focal calcification, limited to the pancreas head, body, or tail; and diffuse calcification (DC), with calcification in >2 sections. Maximum changes in outcomes were seen in the DC vs focal calcification group. In the DC group, preoperative hemoglobin A1c levels were higher (P < .01), and stimulated C-peptide levels were lower (P < .01) than in the NC group. Islet isolation from the DC pancreas resulted in the lowest islet equivalent (IEQ) yield and IEQ/kg among the 3 groups (P < .0001), with no insulin independence 12 months posttransplant (P < .05 vs NC group). Notably, at 12 months, the DC group was 91.7% narcotic-free, significantly higher than the NC group (P < .05). Although DC is a sign of diabetes risk after TPIAT, the DC group showed exceptional pain relief. These findings suggest that TPIAT can be beneficial for patients with chronic pancreatitis with severe calcification.

Nutritional Risks in Patients Undergoing Total Pancreatectomy Islet AutoTransplantation in the POST Consortium

Background and AimsTotal pancreatectomy with islet autotransplantation (TPIAT) can relieve pain for individuals with acute recurrent or chronic pancreatitis. However, TPIAT may increase the risk of poor nutritional status with complete exocrine pancreatic insufficiency, partial duodenectomy, and intestinal reconstruction. Our study's objective was to evaluate nutritional status, anthropometrics, and vitamin levels before and after TPIAT. MethodsThe multicenter Prospective Observational Study of TPIAT (POST) collects measures including vitamins A, D, and E levels, pancreatic enzyme dose, and multivitamin (MVI) administration before and 1-year after TPIAT. Using these data, we studied nutritional and vitamin status before and after TPIAT. Results348 TPIAT recipients were included (68% adult, 37% male, 93% Caucasian). In paired analyses at 1-year follow-up, vitamin A was low in 23% (vs 9% pre-TPIAT, p < 0.001); vitamin E was low in 11% (vs 5% pre-TPIAT, p = 0.066), and 19% had vitamin D deficiency (vs 12% pre-TPIAT, p = 0.035). Taking a fat-soluble multivitamin (pancreatic MVI) was associated with lower risk for vitamin D deficiency (p = 0.002). Adults were less likely to be on a pancreatic MVI at follow-up (34% vs 66% respectively, p < 0.001). Enzyme dosing was adequate. More adults versus children were overweight or underweight pre- and post-TPIAT. Underweight status was associated with vitamin A (p = 0.014) and E (p = 0.02) deficiency at follow-up. ConclusionsPrevalence of fat-soluble vitamin deficiencies increased after TPIAT, especially if underweight. We strongly advocate that all TPIAT recipients have close post-operative nutritional monitoring, including vitamin levels. Pancreatic MVIs should be given to minimize risk of developing deficiencies.

Medzinárodná autotransplantácia Langerhansových ostrovčekov do portálneho riečiska po totálnej pankreatektómii u pacienta s chronickou hereditárnou pankreatitídou – kazuistika a prehľad súčasnej literatúry

Summary: Chronic pancreatitis with repeated painful relapses is a severe multifactorial, fibroinflammatory syndrome that significantly affects the quality of life of patients, mainly in terms of pain, development of diabetes mellitus, and repeated attacks of acute pancreatitis. Autologous islet transplantation after total pancreatectomy is a potential option in selected patients with severe, recurrent painful episodes of chronic pancreatitis. In our case, we present a patient with severe recurrent chronic pancreatitis. The patient required frequent hospitalizations with repeated stenting of the pancreatic duct. After the confirmation of a genetic mutation, the members of the multidisciplinary session decided to perform a total pancreatectomy with islet autotransplantation. In this case, we present the first international islet cell autotransplantation of Langerhans islets in Slovakia after total pancreatectomy in a patient with chronic hereditary pancreatitis. Key words: hereditary pancreatitis – total pancreatectomy – autotransplantation of Langerhans islets

Diabetes-Related Quality of Life Assessment in Children following Total Pancreatectomy with Islet Autotransplantation

Total pancreatectomy with islet autotransplantation (TPIAT) can improve pain and reduce functional impairment associated with acute recurrent or chronic pancreatitis. However, long-term glucose monitoring and insulin therapy are often required, which can adversely affect the quality of life. We sought to evaluate diabetes-related quality of life (DR-QOL) in youth who underwent TPIAT and compare it to the youth with new-onset type 1 diabetes (T1D). The Pediatric Quality of Life Inventory™ 3.2 Diabetes Module (PedsQL™ DM) was used to assess DR-QOL in 46 youth (&lt;20 years old) who underwent TPIAT. The PedsQL™ DM scores were analyzed for statistically significant changes and minimally important clinical differences (MCID) over time post-TPIAT. Scores at 12 months (n = 29) and 24 months (n = 16) were then compared to PedsQL™ DM scores from a historical cohort of demographically similar (age and sex) youth with a 12 months (n = 52) and 24 months (n = 58) after diagnosis of T1D. The diabetes symptoms summary score (mean 65 to 57 and p = 0.03 ) and the total score (mean 74 to 68 and p &lt; 0.05 ) decreased (worsened) during the first 24 months post-TPIAT and met the MCID threshold, suggesting the decrease in these scores was clinically significant. Post-TPIAT PedsQL™ DM scores were not significantly different than youth new diagnosis of T1D after 24 months (all p &gt; 0.2 ). In youth who underwent TPIAT, DR-QOL worsened over the first two years, mostly attributable to the diabetes symptoms score. Compared to children with T1D, post-TPIAT DR-QOL was similar two years after diabetes onset.

839-P: Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation

Stress-induced islet graft loss reduces the efficacy of islet transplants. In this single-center, randomized, double-blind, and controlled clinical trial, we evaluated the safety and efficacy of human alpha-1 antitrypsin (AAT) infusion in chronic pancreatitis (CP) patients undergoing total pancreatectomy and islet autotransplantation (TP-IAT) at the Medical University of South Carolina. Among 48 qualified subjects randomized in a 1:2 (placebo vs AAT) ratio, 43 received TP-IAT. Subjects were given saline or AAT infusion at 60mg/kg weekly for 4 weeks and were followed for 12 months. The primary efficacy endpoint was the islet function measured by the C-peptide area under the curve during a mixed meal tolerance test (MMTT) at Month 12 (M12). Adverse events (AEs) were measured throughout the study. Safety, glycemic control, insulin use, and quality of life (QoL) were compared between groups. Safety evaluation showed no significant differences in the types and severity of participant AEs. The primary efficacy outcome was not significantly different between groups. Baseline characteristics including age, body weight, BMI, HbA1C, etc, were comparable in the randomized populations. The oxygen consumption rate before the transplant was higher in the AAT group. Serum C-peptide (an indicator of islet death) was lower in the AAT group, suggesting less islet injury. AAT subjects trended toward better SF-12 physical QoL and lower insulin use at both 75 and 365 days post-IAT. Despite intensive efforts to get participants to return for the Day 365 MMTT, only 10/14 (71%) in the placebo group and 18/29 (62%) in the AAT group returned for this test. Although we did not observe a statistical difference in islet function using AAT therapy, we gained a better understanding of this patient population. Minimizing numbers of follow-up visits, use of fewer doses of medication with higher doses, and providing travel are all important for future clinical trials in TP-IAT. Disclosure H. Wang: None. W. Gou: None. D. Adams: None. K. Morgan: Speaker's Bureau; Johnson &amp; Johnson Medical Devices Companies. P.J. Nietert: None. J. Hirsch: None. C. Strange: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK105183, DK120394, DK118529); U.S. Department of Veterans Affairs (I01BX004536 to H.W.)

241-OR: Preservation of Islet Graft Function and Blood Glucose Control after Total Pancreatectomy with Islet Autotransplantation in Patients with Chronic Pancreatitis and Intractable Pain—Nine-Year Follow-up

Background: Total pancreatectomy is a last resort treatment for patients with chronic pancreatitis and intractable abdominal pain, however its utility has been hampered by the uncertain endocrine outcomes of islet transplantation and risk of postsurgical diabetes. Here, we present our 9-year clinical results after total pancreatectomy and islet transplantation. Materials and Method: Forty-one patients with chronic or recurrent acute pancreatitis were treated with TPIAT over the last 9 years at the University of Chicago Medical Center. There were 15 male and 26 female with a median age of 33 (6-65) and with median BMI of 25 (17-39). Five (12%) patients were already diabetic prior to surgery. Islet isolation was performed at a local laboratory compliant with current Good Manufacture Practice regulations. Islet purification was implemented in 4 (10%) cases to reduce islet pellet volume below 20mL for intraportal infusion. Results: All patients required opioids for pain control prior to surgery. Most of the patients (93%) reported resolution of pancreatic-type pain by postoperative year one. The number of patients requiring opioids for different type or location of pain declined over time from 13 (31%) at 1 year to 5 (12%) at 5 years after TPIAT. During TPIAT patients received on average 211,000±111,000 islet equivalents (IEQ), 2,500±1,600,). The majority of patients (95%) maintained endocrine beta cell function during follow up (serum c-peptide &amp;gt;0.5ng/ml). Over 40% of patients maintained long-term insulin independence: 44% (15/34) at 1-year and 45% (5/11) at 5-year follow-up. Conclusions: TPIAT successfully provided pancreatic pain resolution of pancreatic pain and preservation of the endocrine beta cell function in majority of the patients with no mortality. Islet autotransplantation prevented diabetes in over 40% of patients. Disclosure W.Lin: None. L.Wang: None. M.Tibudan: None. R.Barth: None. J.Fung: None. P.Witkowski: Advisory Panel; Vertex Pharmaceuticals Incorporated, Novartis. M.Ogledzinski: None. S.Gondek: None. K.Milejczyk: None. B.Juengel: None. L.Potter: None. P.J.Bachul: None. L.Basto: None. L.Perea: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (P30DK020595)

242-OR: Defining Targets for Continuous Glucose Monitoring (CGM) after Total Pancreatectomy with Islet Autotransplantation (TPIAT)

Targets for continuous glucose monitoring (CGM) are well established for type 1 and type 2 diabetes. In total pancreatectomy with islet auto-transplant (TPIAT), stricter glycemic targets are needed to avoid metabolic stress on transplanted islets, but no guidelines exist for CGM targets. We aimed to determine CGM targets for TPIAT clinical management by associating CGM metrics with goal hemoglobin A1c (HbA1c) ≤6.5%. Targets for time in range (TIR) 70-140, TIR 70-180, mean CGM glucose, and time in hyperglycemia (&amp;gt;140, &amp;gt;180, &amp;gt;250 mg/dL) were chosen to give good sensitivity and specificity for identifying HbA1c ≤6.5%. We included 256 episodes of 14-day CGM metrics with a concurrent HbA1c value (n=82 patients, age 32.8 [SD 16.6] years at surgery, 70% female) who were ≥0.5 years post TPIAT (median 4.1 years) and wearing Dexcom G6. Most patients had more than 1 HbA1c and corresponding CGM available (median 3.1 per patient). As expected, CGM metrics correlated highly with each other. Table 1 shows “best” (Youden criterion) CGM thresholds and sensitivity for HbA1c ≤6.5%. TIR 70-140 mg/dL ≥50% and TIR 70-180 mg/dL ≥75% may be reasonable targets for patients and providers using CGM data to manage diabetes long-term after TPIAT. Also, time in hyperglycemia should be kept to &amp;lt;20% above 180 mg/dL and &amp;lt;3% above 250 mg/dL. Failure of these goals should prompt re-starting or adjusting insulin therapy. Disclosure Z.Somani: None. J.S.Hodges: None. K.Ramanathan: None. S.Chinnakotla: None. G.Beilman: None. M.Bellin: Consultant; Insulet Corporation, Vertex Pharmaceuticals Incorporated, Research Support; Dexcom, Inc., ViaCyte, Inc.

239-OR: Glycemic Control after Total Pancreatectomy with Islet Autotransplantation—Results from a Single Center with Large Cohort of Patients

Total pancreatectomy and islet autotransplantation (TPIAT) for refractory chronic pancreatitis has been performed at our center from 2006. We employed anti-inflammatory treatment using IL-1β and TNF-α blockers to improve graft outcomes. We present results on islet characteristics and glycemic control post-TPIAT from this large cohort of patients. Our database of 200 consecutive TPIAT procedures performed were retrospectively reviewed. We collected demographics, pancreas and islet characteristics. Patient follow-ups were performed at 3, 6, 12 m and then annually. Outcomes measures included glycemic control, pain relief and narcotic use. Baseline patient characteristics (age, sex, BMI, etiology, C-peptide and HbA1c, duration of symptoms) and isolation results were shown in Table 1A and post-TPIAT fasting glucose, HbA1c, C-peptide and daily insulin use in Table 1B. The insulin independence rate at 3, 6 and 12 months increased with time from 15%, 24 % and 27%, respectively). At 1 year, pain score was significantly improved (p&amp;lt;0.0001). Narcotic free rate also increased to 47% at 6 months and 56% at 1 year. Most post-TPIAT patients preserved hypoglycemic awareness and good pain relief. A cohort of patients remained normoglycemic without insulin and this group can be further studied to identify the factors that prevent the incidence of T3cDM after TPIAT. Disclosure A.Hakim mohammed: None. C.Darden: None. J.Kirkland: None. J.Kuncha: None. J.D.Mattke: None. M.C.Lawrence: None. B.Naziruddin: None.

1481-P: Islet Cell Autoantibody Formation and Its Effect on Insulin Requirement after Total Pancreatectomy with Islet Autotransplantation (TPIAT)

Introduction: Long term insulin requirements following TPIAT range from insulin independence to full (high) dose daily insulin (&amp;gt;0.5 units/kg/day). Markers of islet cell autoimmunity are used in children to predict type 1 diabetes risk. However, no studies have explored whether an association exists between islet cell autoimmunity and insulin requirement following TPIAT in children. We hypothesized that children with islet cell autoantibody formation were more likely to have a persistent insulin requirement following TPIAT. Methods: All children who underwent TPIAT between 2015 and 2021 at our institution were eligible for inclusion. Islet cell autoimmunity was defined as positive islet cell autoantibody screen for one or more of the following types of autoantibodies: Glutamic Acid Decarboxylase (GAD), Islet Antigen-2 (IA-2), Insulin (IAA), or Zinc Transporter 8 (ZnT8). Patients were screened prior to TPIAT and every six months following TPIAT for up to three years. In all, 73 patients were included in the analysis. Total daily insulin dose was determined for each patient at each time interval. Chi-square or Fisher’s exact tests were used to compare proportions. Results: Of patients with 12-month data (n=38), 47% of islet cell autoantibody negative patients were off insulin vs 26% of antibody positive patients (p=0.19). This trend was significant at 18, 24, and 36 months after TPIAT. At 18 months, 90% (9/10) of antibody negative patients were off insulin vs 29% (4/14) of antibody positive patients (p=0.005). At 24 months, 73% (8/11) of antibody negative patients were off insulin vs 23% (3/13) of antibody positive patients (p=0.04). At 36 months, 100% (8/8) of antibody negative patients were off insulin compared to 0% (0/9) of antibody positive patients (p&amp;lt;0.0001). Conclusions: The presence of pancreatic islet cell antibodies was associated with persistent insulin requirement after TPIAT. Disclosure A.R.Lavik: None. C.M.O.Lowe: None. S.E.Tellez: None. L.Hornung: None. C.Heinzman: None. J.D.Nathan: None. M.Abu-el-haija: None. D.A.Elder: None.

161-LB: Diagnosis and Treatment of Diabetes Mellitus in Pediatric Patients with Pancreatitis Followed in a Multidisciplinary Clinic

Children with recurring acute or chronic pancreatitis are at risk for pancreatitis related diabetes mellitus (DM). Pancreatic endocrine and exocrine concerns are managed by different subspecialists. Our center has a unique pediatric pancreatitis multidisciplinary clinic (MDC) with pediatric gastroenterology, endocrinology, pain, and nutrition experts. We obtain point-of-care (POC) HbA1c during clinic check-in for immediate DM screening. Our study describes the utility of POC HbA1c testing in our MDC. We analyzed a retrospective chart review of MDC patients from 2018-2023 with a diagnosis of pancreatitis and DM (n=27). Twelve were diagnosed with DM prior to presentation and 2 presented after total pancreatectomy with islet autotransplantation (TPIAT). Eight patients eventually developed DM and 5 later underwent TPIAT resulting in DM. We evaluated baseline characteristics at presentation to our MDC and longitudinal follow up. Of the 12 patients with previously diagnosed DM, 42% were Hispanic/Latino, 50% were female. On presentation to the MDC, patients were 15.4±2.1 years old with BMI 23.2±4.0 kg/m2 and HbA1c 9.6±2.9%. Eight patients developed DM within 1.1±1.2 years of follow up. Six were diagnosed by POC HbA1c in our MDC. Of all whom developed DM, 88% were Hispanic/Latino, 88% were female. DM was diagnosed at 14.3±1.6 years old with BMI 34.5±4.8 kg/m2 and HbA1c 8.5±2.5%. Of our 27 patients with DM, 4 had type 1 DM autoantibodies. At most recent visit HbA1c was 8.9±3.2%. DM treatment involved oral agents (15%), insulin (85%) and nutrition counseling for all patients. Total daily dose of insulin was 0.75±0.53 u/kg/day and 48% of patients used continuous glucose monitors. Instituting POC HbA1c screening in pancreatitis clinic identifies patients with new onset DM, supporting multidisciplinary care. Despite intensive care, HbA1c for these patients remains above guideline goals. More research is needed in providing DM care for children with pancreatitis. Disclosure E. Vargas: None. J. Mark: None. G. P. Forlenza: Advisory Panel; Medtronic, Consultant; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., Lilly Diabetes, Research Support; Medtronic, Abbott, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. T. M. Triolo: None.

1495-P: Bionic Pancreas-3D Bioprinting of Pancreatic Tissue Petals—Results of Transplantation in Large Animals

The first milestone of a new therapy for the treatment of T1D is the development of 3D bioprinted petals consisting of: pancreatic islets and biomaterials. The aim of the study was to demonstrate the functionality of pancreatic islets in in vivo studies on large animals. Material and Methods: Domestic pigs were the research model. The animals were divided into 4 groups:(1)healthy pigs (Control; n=3);(2) animals with T1D after pancreatectomy, treated with insulin (T1D;n=3);(3) animals after pancreatectomy and autotransplantation of pancreatic islets to the liver (LIVER; n=3);(4) animals with T1D after pancreatectomy, which were autotransplanted with bionic petals (3D-PETALS; n=3). The effectiveness of the transplantation (TX) was assessed by the concentration of glucose, insulin intake and C-peptide. The observation lasted 1 month. Results: The results showed that in the LIVER group, insulin intake within 3 weeks decreased by 71% compared to the demand before TX. Whereas 1 month after TX, the demand was lower by 62%. The 3D-PETALS group showed that the insulin intake in 3 weeks after TX decreased by 65%, and within a month decreased by 84%. In the 4th week after TX, the insulin intake average in the T1D group was 8.17U, while in the LIVER group=2.44U and in the 3D-PETALS group=1.06U. Islet TX significantly reduced insulin intake (T1D vs LIVER; p=0.0001 and T1D vs 3D-PETALS; p&amp;lt;0.0001). Glucose measurement showed significant changes. After 1 month of follow-up, glucose levels were significantly lower in the LIVER vs T1D (265.8mg% vs 310.2mg%; p&amp;lt;0.0001) and 3D-PETALS &amp; T1D (198.3mg% vs 310.2mg%; p=0.0354). Most importantly, glycemic levels were also significantly lower between the LIVER &amp; 3D PETALS groups (265.8mg% vs 198.3mg%; p=0.0021). The concentration of C-peptide during the study was 0.14ng/ml. Conclusion: Bioprinted petals with dECM-based bioink significantly reduces diabetic parameters. Thus, it seems to be an effective therapy for people with T1D. Disclosure M.Klak: Employee; Polbionica Sp. z o.o., Stock/Shareholder; Polbionica Sp. z o.o. A.Berman: Board Member; Polbionica Ltd., Stock/Shareholder; Polbionica Ltd. O.Janowska: Employee; POLBIONICA Sp. z o.o. S.Domanski: Employee; Polbionica. D.Szkopek: None. K.I.Roszkowicz-ostrowska: None. A.Kondej: None. J.Wolinski: None. M.Wszola: Board Member; Polbionica Ltd., Stock/Shareholder; Polbionica Ltd.

Metabolic Outcomes in Pediatric Patients One-Year Post-Total Pancreatectomy with Islet Autotransplantation after Early Pump Initiation.

We previously published that insulin pump initiation immediately after IV insulin therapy was associated with improved post-surgical glycemic outcomes compared to multiple daily injections (MDI) in pediatric patients following a total pancreatectomy with islet autotransplantation (TPIAT). We investigated metabolic outcomes of this population at one-year post-TPIAT to assess if the improved outcomes in the early pump group were sustained over time. We retrospectively reviewed 40 patients post-TPIAT previously studied at 10-days post-surgery (15 used MDI and 25 used pump therapy immediately post-ICU, and all were discharged on pump therapy). Data analyzed included: demographics, islet equivalents per kilogram (IEQ/kg) transplanted, exogenous insulin use, and baseline vs. one-year (via mixed meal testing) HbA1c, fasting glucose, insulinogenic index, and the area under the curve (AUC) for insulin and c-peptide. More patients were off insulin at one year in the early pump group compared to the MDI group (45% vs. 13%, p = 0.07). Of all patients off insulin, 100% of the early pump users weaned off by six months post-TPIAT compared to 30% of the MDI users. Two known variables associated with favorable insulin outcomes, lower age and higher IEQ/kg, were not significantly different between groups. Fasting glucose was lower in the early pump group compared to the MDI group (median 97 vs. 122 mg/dL, p = 0.003), while AUC c-peptide was greater in early pump users at one-year post-TPIAT but did not reach significance (median 57.0 vs. 50.3 ng/mL × minutes, p = 0.14). Other metabolic outcomes did not differ between groups. Despite lower median age and higher IEQ/kg in the MDI group, the early pump group had a lower fasting glucose. Younger TPIAT age (p = 0.02) and early pump users (p = 0.04) were significantly associated with insulin independence at one year. This study was limited by sample size. Early pump use may have long-term benefits in post-TPIAT endogenous insulin secretion.