Introduction and Objective: Total pancreatectomy with islet autotransplantation (TPIAT) requires families to manage diabetes with insulin pumps and continuous glucose monitors post-operatively at our institution. We created a structured pre-TPIAT diabetes education program that used condition-specific content to increase the primary learner’s preparedness for post-surgical diabetes management and improve the efficiency of subsequent inpatient education. Methods: This quality improvement study analyzed 33 pediatric TPIAT recipients at Cincinnati Children’s who received structured pre-surgery education across three Plan-Do-Study-Act (PDSA) cycles. Data were extracted from clinical records and survey responses collected. Qualitative survey data were collected from Cycle 3 participants only. Results: The cohort was predominantly White (87.9%), non-Hispanic (97.0%), with balanced sex distribution (48.5% female). Mean age at surgery was 12.2 years. Parents served as primary learners in 87.9% of cases. Pre-surgery education time showed highly statistically significant increases in Cycles 2 and 3 compared to Cycle 1 (p=0.0291 and p=0.0007, respectively). Basic inpatient diabetes education time showed a marginally significant decrease from Cycle 1 to Cycle 2 (p=0.0717) which was maintained in Cycle 3 (0.3285). Survey results demonstrated substantial knowledge acquisition from the education intervention. Conclusion: Changes in TPIAT diabetes education delivery were implemented and improved technical knowledge. A modest decrease in inpatient diabetes education time was documented from cycle 1 to cycles 2 and 3. Future confirmatory studies will validate the knowledge gains observed in this pilot. Next steps include assessing longer-term knowledge retention and incorporating stress management into education sessions. Disclosure S. Tellez: None. C. Fox: None. A.K. Essell: None. L. Lin: None. M. Abu El Haija: None. D.A. Elder: Research Support; Current; Sanofi.

Objective: This study aimed to describe the frequency of exocrine pancreatic disease in youth with diabetes. Methods: We conducted a retrospective chart review on data that was obtained from a single-center prospectively collected database of patients with diabetes. Patients were categorized as having type 1 diabetes, type 2 diabetes, or "Other" diabetes if they had cystic fibrosis-related diabetes, maturity-onset diabetes of the young, or drug/chemical-induced diabetes. All patients' charts were reviewed for exocrine pancreas disease, inclusive of pancreatitis or exocrine pancreatic insufficiency. Results: Nine hundred eighty-eight patients with a diabetes diagnosis were included. Thirty-five out of 988 (3.5%) were diagnosed with pancreatic exocrine disease. Diabetes patients with exocrine disease compared with the ones without were significantly older (13.1 y, IQR 9.8-15.3 vs. 11.7 y, P= 0.04). Those with exocrine disease were more likely to have "Other" diabetes (P<0.0001). The exocrine group had a lower median hemoglobin A1c at diabetes diagnosis (7%, IQR 5.8%-9.2% vs. 11.3%, 8.9%-13.8%; P<0.0001). Out of the 988 patients, 18 patients had pancreatitis diagnosed, which was 2% of the overall cohort. Nine of the 18 patients were found to have developed pancreatitis after diabetes diagnosis, or 1% of the entire diabetes cohort (9/988). Conclusions: The co-existence of exocrine and endocrine pancreatic disease occurred in 3.5% of diabetes patients. The risk of pancreatitis occurring after diabetes was 1%, a rate 100 times higher than the general pediatric population (0.01%). Future studies are needed to determine the specific mechanisms involved in the connection between endocrine and exocrine pancreatic disease in children.

BACKGROUND:Adolescents with severe obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) lack prospective comparative evidence to select between bariatric surgery and intensive lifestyle intervention. AIMS:To compare 52-week histological and cardiometabolic outcomes of vertical sleeve gastrectomy (VSG) versus comprehensive lifestyle intervention (CLI). METHODS:Single-centre, prospective, parallel-arm study of adolescents aged 12-19 with severe obesity and biopsy-confirmed MASLD with NAFLD Activity Score (NAS) ≥ 3. The primary endpoint was NAS ≥ 2-point decrease without fibrosis worsening; secondary endpoints included MASH resolution, fibrosis regression, MRI proton density fat fraction (MRI-PDFF) and elastography (MRE). Overlap-weighted adjusted analysis addressed baseline imbalance. Conservative unadjusted intention-to-treat analogue analyses treated missing Week 52 histology as nonresponse and missing continuous outcomes as no change. RESULTS:Forty-two adolescents enrolled (VSG = 17; CLI = 25) and 27 (64%) completed paired Week 52 histology. In the adjusted analysis, VSG was associated with a higher probability of NAS improvement (risk difference [RD] 0.68, 95% CI 0.45-0.91), fibrosis improvement (RD 0.36, 95% CI 0.12-0.59) and complete MASLD resolution (RD 0.49, 95% CI 0.26-0.72) when compared to CLI. VSG produced greater reductions in percent weight (-19.6%, 95% CI -30.0 to -9.1), percentage of the 95th percentile BMI (-27.6%, 95% CI -42.6 to -12.7), ALT (-54.0 U/L, 95% CI -80.8 to -27.1) and MRI-PDFF (-8.0%, 95% CI -13.0 to -2.9). Findings were directionally consistent in conservative unadjusted intention-to-treat and paired-biopsy completer analyses. CONCLUSION:In this prospective cohort of adolescents with severe obesity and biopsy-confirmed MASLD, VSG achieved greater 52-week histological improvement, including steatosis and fibrosis, than CLI. TRIAL REGISTRATION:ClinicalTrials.gov identifier: (NCT02412540).

Fanconi anemia (FA) is a rare inherited disorder characterized by progressive bone marrow failure (BMF) and a predisposition to malignancy. Systemic reactive-oxygen species (ROS) and increased sensitivity of FA hematopoietic progenitors to ROS play a key role in the pathogenesis of BMF. Treatment with antioxidants improve hematopoietic function in Fancc-/- mice. We report the safety, tolerability, and pharmacokinetics (PK) of quercetin, a naturally occurring antioxidant in the first dose-finding Phase 1 study in patients with FA. Twelve patients (median age 7 years, range: 3-21) received oral quercetin twice daily for 4 months. Quercetin was well tolerated at all dose levels. Allometrically bodyweight-adjusted dose with a maximum adult daily dose of 4000mg/day was established as the recommended dose of quercetin. Patients in an expansion cohort (n=18) were treated using this recommended dose for 6 months. A subset of patients showed reduced ROS levels in the peripheral blood and bone marrow stem cell compartment. Patients in the analysis cohort treated with the recommended dose of quercetin achieved an a priori defined optimal response of 25% reduction in the peripheral blood (PB) ROS level compared to baseline. Platelet counts remained stable to slightly improved over the study period (p=0.06). Absolute neutrophil counts (p=0.01) and hemoglobin levels gradually declined (p=0.001). In those with evidence of BMF at baseline, 8 out of 15 patients (53%) had a hematological response at some point following quercetin treatment. Fluctuations in counts are common in patients with FA limiting accurate assessment of the impact of quercetin use in FA. NCT# 01720147

Introduction and Objective: Total pancreatectomy with islet auto transplantation (TPIAT) is a non-immune model of islet transplant. The presence of islet autoantibodies post TPIAT has been observed, but the impact on β cell function is unknown. We compared measures of β cell function between children who were islet autoantibody positive (IAP) and negative (IAN) for up to 2 years post TPIAT. Methods: Clinical data was collected from children who underwent TPIAT between 2015 and 2021. All patients were screened for islet autoantibodies and underwent Mixed Meal Tolerance Testing (MMTT) at 12 months and 18-24 months post TPIAT. IAP was defined as the detection of one or more of the following: Glutamic Acid Decarboxylase (GAD), Islet Antigen-2 (IA-2), or Zinc Transporter 8 (ZnT8). Insulin Antibody (IAA) was excluded due to the likelihood that detection was secondary to exogenous insulin exposure. At 12 months, 23 patients were identified: 7 IAP and 16 IAN. At 18-24 months, 20 patients were identified: 7 IAP and 13 IAN. Results: There were no differences in age at TPIAT, sex, or HbA1C levels between patients who were IAP or IAN. At 12 months post TPIAT, insulinogenic index, peak C peptide, C peptide secretion index and area under the curve C peptide were higher in the IAP group. BMI was significantly higher in the IAP group at 12 and 18-24 months. At 18-24 months, although not statistically significant, the median age was lower in the IAN group. Conclusion: The role of islet autoantibodies on β cell function post TPIAT remains unclear. IAP group is associated with increased insulin secretion post TPIAT. These data suggest that age and BMI influenced insulin secretion more than the presence of islet autoantibodies over this short post TPIAT duration. We suspect a longer exposure to islet antibodies is required to assess impact on β cell function. O. Kothawala: None. L. Hornung: None. A.R. Lavik: None. S. Swauger: None. C.M.O. Lowe: None. M. Abu-El-Haija: None. S.E. Tellez: None. D.A. Elder: Research Support; Dexcom, Inc., Sanofi.

Background:The increasing use of continuous glucose monitor (CGM) necessitates a review of variables that impact accuracy and interrupt use. Manufacturer recommendations include removing CGMs before diagnostic imaging, such as X-ray and computed tomography (CT). Early removal and replacement of CGM components present financial, clinical, and psychosocial burdens to the wearer and interrupt optimal management of diabetes for pediatric patients who receive a total pancreatectomy with islet autotransplantation (TPIAT). The study's aim was to evaluate the effect of scatter dose exposure during X-ray or CT if the CGM remained intact but outside the field of view (FoV). Materials and Methods:Participants were followed through the first 3 months after TPIAT surgery, managed diabetes with an insulin pump and CGM, and were routinely exposed to diagnostic imaging. Participants' CGMs were unshielded by a protective apron during any X-ray or CT procedures for the duration of the study period, and the transmitter was collected after expiration or removal. Glucometer data was collected from hospital records and home glucometer downloads. Mixed models were used to analyze absolute differences between matched CGM and glucometer values, and Clarke error grid analyses (EGA) were performed. Scatter dose exposure was derived using anthropomorphic phantoms and calculated retrospectively. Results:A total of 14 patients (median 12.2 years, 64% female) received a median of five diagnostic imaging procedures with a median cumulative scatter dose of 559 µGy. The absolute difference between the CGM and glucometer values was not significantly associated with the cumulative scatter dose (p=0.17) or time from TPIAT (p=0.24) when analyzed in a mixed model. Regardless of scatter dose exposure, time from TPIAT, or glucometer, ≥98% of glucose values fell within zones A and B on EGA. Conclusion:Scatter dose exposure from diagnostic imaging did not affect the clinical accuracy of CGM values for the duration of transmitter use. Leaving CGM components in place when not in the FoV during diagnostic imaging successfully mitigated interruptions to use and undue burden or cost to participants.

Introduction & Objective: This study aimed to describe the frequency of exocrine pancreatic disease in youth with diabetes mellitus (DM) to better understand the connection between diseases of the endocrine and exocrine pancreas. Methods: Data was obtained from a single center database of DM patients excluding pre-DM and neonatal DM diagnosis. Patients were categorized as having “Other” DM if they had CFRD, MODY, or drug/chemical induced DM. All patients were then evaluated for exocrine pancreas disease, inclusive of pancreatitis or pancreatic insufficiency. Results: Nine hundred ninety-one patients with DM diagnosis were included and 37/991 (4%) were diagnosed with pancreatic exocrine disease. 11/991 had pancreatitis before DM while 9/991 developed pancreatitis post DM. There were no differences in age, race/ethnicity and sex between DM youth with and without exocrine disease or between those with vs without pancreatitis. Patients with exocrine disease were more likely to have “Other” DM and a lower median hemoglobin A1c at DM diagnosis (6.8% IQR 5.6-9.2% vs 11.2%, 8.9-13.8%; p<0.0001). Excluding those with T1D, those with exocrine disease were more likely to have received insulin therapy (8/37, 22% vs 11/954, 1.2%; p<0.0001) than youth with DM and no exocrine problem. Patients with pancreatitis at any time relative to DM diagnosis were more likely to have “Other” DM and less likely to have T1D (p<0.001), had a lower median A1c (8%, IQR 5.8-9.4% vs 11.2.%, IQR 8.9-13.8%; p=0.0004), and more likely to have received insulin therapy but not have T1D (6/20, 30% vs 11/954, 1.2%; p<0.001). Conclusions: The co-existence of exocrine and endocrine pancreatic disease occurred in 4% of DM patients. Pancreatitis occurred at a rate of 1% in patients with DM, rates higher than the general population (0.01%). Future studies are needed to determine the specific mechanisms involved in the connection between the endocrine and exocrine pancreas in children. Disclosure J.D. Tatum: None. L. Hornung: None. D.A. Elder: Research Support; Dexcom, Inc. A.S. Shah: None. M. Abu-El-Haija: None.

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 (<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 < 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 > 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.

Objective: To describe management strategies that contributed to optimal outcomes in pediatric recipients of a total pancreatectomy with islet autotransplantation (TPIAT). Research Design and Methods: We provide a comprehensive report of the approach to endocrine management of the pediatric TPIAT recipient from initial evaluation through the first 4 years postsurgery. We performed a retrospective review of the endocrine outcomes of TPIAT recipients to describe the impact of this approach on post-TPIAT glycemic management. Results: Outcome data from 86 TPIAT recipients were reviewed. At 12 months post-TPIAT (n = 82), the median HbA1C was 6.0% (25-75th percentile 5.6-6.7), at 18 months (n = 56) HbA1C was 6.4% (5.6-7.5), at 2 years (n = 46) HbA1C was 6.4% (5.6-7.4), at 3 years (n = 31) HbA1C was 6.5% (5.5-8.1), and at 4 years (n = 16) HbA1C was 7.2% (6.2-8.3). Conclusions: Pediatric patients at our institution have favorable endocrine outcomes as evidenced by median HbA1C under the goal of 6.5% through the initial 3 years by following our modified management protocols.

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.

The relationship between pancreatic fat on imaging and metabolic co-morbidities has not been established in pediatrics. We sought to investigate the relationship between pancreatic fat measured by MRI and endocrine/exocrine dysfunctions along with the metabolic co-morbidities in a cohort of children. To investigate relationships between pancreatic fat quantified by MRI and endocrine and exocrine conditions and metabolic co-morbidities in a cohort of children. This was a retrospective review of pediatric patients (n = 187) who had a clinically indicated MRI examination between May 2018 and February 2020. After 51 patients without useable imaging data were excluded, the remaining 136 subjects comprised the study sample. Laboratory studies were assessed if collected within 6 months of MRI and patient charts were reviewed for demographic and clinical information. MRI proton density fat fraction (PDFF) sequence had been acquired according to manufacturer’s specified parameters at a slice thickness of 3 mm. Two blinded radiologists independently collected PDFF data. The median age at MRI was 12.1 (IQR: 9.0–14.8) years and the majority of patients were Caucasian (79

Introduction. The underlying pathophysiology of diabetes mellitus after acute pancreatitis is unknown and overall risk of developing diabetes postacute pancreatitis in children is understudied. The objective of our study was to describe the frequency of islet cell autoimmunity and abnormal glucose testing in pediatric patients in the year following their index case of acute pancreatitis. Materials and Methods. Data were obtained from a single-center observational cohort study of patients with their first episode of acute pancreatitis. Islet cell autoantibody titers were measured on stored plasma collected from acute pancreatitis diagnosis, at 3 months and at 12 months postacute pancreatitis attack. Abnormal glucose testing was defined as the presence of prediabetes or diabetes, as defined by American Diabetes Association criteria. Results. Eighty-four patients with acute pancreatitis and islet cell autoantibody data were included, 71 had available glucose measures. Median age at first acute pancreatitis attack was 14 years (IQR 8.7–16.3) and 45/84 (54%) were females. Twenty-four patients (29%) were positive for at least one of four islet cell autoantibodies (IAA, GADA, IA-2A, and ZnT8A) and 6 (7%) had two or more positive islet cell autoantibodies. Nineteen patients out of 71 (27%) had abnormal glucose testing at or postacute pancreatitis diagnosis. A higher proportion (37%, 7/19) with abnormal glucose testing had severe acute pancreatitis compared to those with normal glucose testing (13%, 7/52) ( p = 0.04 ). Patients with normal glucose testing were more likely to be positive for one or more islet cell autoantibodies (31%, 16/52) compared to those with abnormal glucose testing (0%, 0/19) ( p = 0.004 ). Conclusions. Islet cell autoimmunity is more common in children after their index acute pancreatitis attack (29%) than in the general population (7%–8%). While the frequency of prediabetes and diabetes postacute pancreatitis is high, other mechanisms besides islet cell autoimmunity are responsible.

Introduction: Long term insulin requirements following TPIAT range from insulin independence to full (high) dose daily insulin (>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<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.

Objective: Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at one year following TPIAT in a cohort of children. Research Design and Methods: This was a review of 43 pediatric patients followed after TPIAT for one year or longer. Primary outcome was insulin use at one year, categorized as: insulin independent, low (< 0.5 u/kg/day) or high insulin (≥ 0.5 u/kg/day) requirement. Results: At one year after TPIAT, 12/41 (29%) patients were insulin independent, 21/41 (51%) had low and 8/41 (20%) had high insulin requirement. Insulin independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; p=0.03). Patients with insulin independence had higher transplanted IEQ/kg (p=0.03) and lower body surface area (p=0.02), compared to those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (p=0.03). Higher peak C-peptide measured by stimulated mixed meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at one year (p=0.006 and 0.03, respectively). Conclusions: We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ/kg transplanted and lower body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement.

ABSTRACT Children with acute recurrent and chronic pancreatitis (CP) experience abdominal pain that leads to hospitalizations, opioid dependence, and poor quality of life. Total pancreatectomy with islet autotransplantation (TPIAT) is offered as a surgical option in management of debilitating pancreatitis that fails medical and endoscopic therapy to reduce or eliminate pain. Given that patients with type 1 diabetes mellitus (T1DM) lack insulin-producing β cells, the outcomes from autotransplanting islet isolates back into total pancreatectomy patients with T1DM are not fully known.We performed TPIAT in 2 CP patients who also had a diagnosis of T1DM for at least 6 years before the operation and evaluated the clinical and laboratory outcomes before and after the operation. Postoperatively both patients' abdominal pain had significantly subsided, they were weaned off opioid medications, and they were able to return to full-time school attendance. In addition, total daily dose of insulin in 1 patient was able to be slightly reduced at 12 months post-TPIAT. We observed in vitro that residual α cells and β cells in T1DM islets were able to secrete a small amount of glucagon and insulin, respectively.

INTRODUCTION:Adult women with Turner syndrome (TS) have a high prevalence of diabetes and β-cell dysfunction that increases morbidity and mortality, but it is unknown if there is β-cell dysfunction present in youth with TS. This study aimed to determine the prevalence of β-cell dysfunction in youth with TS and the impact of traditional therapies on insulin sensitivity (SI) and insulin secretion.METHODS:Cross-sectional, observational study recruited 60 girls with TS and 60 healthy controls (HC) matched on pubertal status. Each subject had a history, physical exam, and oral glucose tolerance test (OGTT). Oral glucose and c-peptide minimal modeling was used to determine β-cell function.RESULTS:Twenty-one TS girls (35%) met criteria for prediabetes. Impaired fasting glucose was present in 18% of girls with TS and 3% HC (p value = 0.02). Impaired glucose tolerance was present in 23% of TS girls and 0% HC (p value <0.001). The hemoglobin A1c was not different between TS and HC (median 5%, p = 0.42). Youth with TS had significant reductions in SI, β-cell responsivity (Φ), and disposition index (DI) compared to HC. These differences remained significant when controlling for body mass index z-score (p values: 0.0006, 0.002, <0.0001 for SI, Φ total, DI, respectively).CONCLUSIONS:β-Cell dysfunction is present in youth with TS compared to controls. The presence of both reduced insulin secretion and SI suggest a unique TS-related glycemic phenotype. Based on the data from this study, we strongly suggest that providers employ serial OGTT to screen for glucose abnormalities in TS youth.

Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure for patients with chronic pancreatitis and poor quality of life. Euglycemia is critical for islet cell survival and engraftment. We reviewed clinical care practice and hypothesized that early in-hospital transition from intravenous insulin to insulin pump therapy, managed by an endocrine unit trained on post-surgical care, would improve glucose control and impact the length of hospital stay. We completed a retrospective analysis of 40 pediatric patients who underwent TPIAT. Comparative hospitalized postoperative groups included those who received insulin intravenously, followed by multiple daily injections, subsequently managed by pump therapy (n = 14), versus those who received insulin intravenously followed by early pump therapy provided on the endocrine unit trained to manage post-surgical patients (n = 26). The outcomes analyzed included percentage of blood glucoses in target (4.44–6.66 mmol/L (80–120 mg/dL)), hypoglycemia (<3.33 mmol/L (<60 mg/dL)) and hyperglycemia (>7.77 mmol/L (>140 mg/dL)), blood glucose variability, and length of hospital unit stay post-ICU. Hospitalized patients with early transition to pump therapy on a specialized endocrine unit had a higher proportion of glucose values in the target range (61% vs. 51%, p = 0.0003), a lower proportion of hyperglycemia (15% vs. 19%, p = 0.04), and a lower proportion of hypoglycemia, though not statistically significant (3.4% vs. 4.4%, p = 0.33). Early pump users also had lower variability in glucose values over 10 days post-intravenous insulin (p = 0.001), and the post-transition median length of stay was shorter by 5 days (median: 11.5 vs. 16.5 days, p = 0.005). Early in-hospital pump therapy managed by the specialized endocrine unit improved glucose outcomes and reduced the duration of in-unit stay.

Prediabetes in youth has become a more frequent challenge facing patients, families, and providers alike. As we learn more about the natural history of prediabetes and T2DM, investigators have found distinct differences between these conditions in youth and adults, making extrapolation of adult practice problematic. Moreover, there is a lack of evidence-based management and treatment guidelines for prediabetes in youth. Although current approaches may differ, best clinical practice indicates that providers should screen at-risk youth for prediabetes, and intervene with intensive lifestyle modification through improved nutrition and exercise. In some cases, pharmacologic intervention may also be warranted, but always in the context of lifestyle and behavioral changes.