Predictors of Glycemic Outcomes at 1 Year Following Pediatric Total Pancreatectomy With Islet Autotransplantation

Abstract

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 1 year following TPIAT in a cohort of children. RESEARCH DESIGN AND METHODS This was a review of 43 pediatric patients followed after TPIAT for 1 year or longer. Primary outcome was insulin use at 1 year, categorized as follows: insulin independent, low insulin requirement (<0.5 units/kg/day), or high insulin requirement (≥0.5 units/kg/day). RESULTS At 1 year after TPIAT, 12 of 41 (29%) patients were insulin independent and 21 of 41 (51%) had low and 8 of 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 a higher number of transplanted islet equivalents (IEQ) per kilogram body weight (P = 0.03) and smaller body surface area (P = 0.02), compared with 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 1 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 per kilogram body weight transplanted, and smaller body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement.

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

“…A p value of <0.05 was considered statistically significant. A subset of these patients was published in other studies with different study design and divergent goals and aims [10,[20][21][22][23][24][25][26][27]. A subset of these patients was enrolled in the Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC) and in the Prospective Observational Study of TPIAT (POST) multicenter study, also under different goals and objectives.…”

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

“…BETA-2 uses fasting glucose, c-peptide, HbA1c, and the total daily insulin dose per kilogram to score beta cell function [9,10]. While Igls 2.0 criteria provides some standardization to the assessment of graft function, use of BETA-2 scoring for pediatric TPIAT recipients to assess post-surgical beta cell function is increasing in the literature and was included in this analysis [4]. Baseline data were defined as the metabolic measures collected within 1 year prior to their TPIAT.…”

“…Informed consent and assent to participate in the Pancreas Care Center clinical registry were obtained from parents and patients. Subsets of this population have been included in prior publications through studies with different designs from the current study [4,[14][15][16].…”

“…The autologous transplant of islet cells from the pancreas, with subsequent maintenance of optimal conditions for islet engraftment, is aimed at potentially (or partially) mitigating insulin-dependent post-pancreatectomy diabetes mellitus [1][2][3]. Some predictors of insulin independence in pediatric TPIAT recipients include an islet yield at the time of surgery (IEQ/kg) > 5000 and younger age at surgery [4]. After TPIAT, the literature suggests that the maintenance of blood glucose in the range of 80-120 mg/dL during the islet engraftment period promotes optimal outcomes [1,5].…”

Micropyramid-patterned, oxygen-permeable bottomed dish for high density culture of pancreatic islets

“…For example, pancreatic islets are the spherical units in the pancreas that typically are 100-500 µm in diameter [15]. Since islets play a critical role in glucose homeostasis as an endocrine micro-organ, isolated islets have been used for the allo-and auto-transplantation to treat a certain type of diabetes when the native islet function is totally impaired [9,[16][17][18][19]. Typically, ∼500 000 islet spheroids (islet equivalent (IEQ) [15]) are isolated from an organ donor to transplant within several days.…”