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

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.

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

Diabetes Care ◽

10.2337/dc21-1222 ◽

2022 ◽

Author(s):

Sarah E. Swauger ◽

Lindsey N. Hornung ◽

Deborah A. Elder ◽

Appakalai N. Balamurugan ◽

David S. Vitale ◽

...

Keyword(s):

Body Weight ◽

Surface Area ◽

Body Surface Area ◽

Body Surface ◽

Total Pancreatectomy ◽

Insulin Requirement ◽

Insulin Independence ◽

C Peptide ◽

High Insulin ◽

Islet Autotransplantation

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.

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SIMPLIFICATION OF DRUG DOSAGE CALCULATION BY APPLICATION OF THE SURFACE AREA PRINCIPLE

PEDIATRICS ◽

10.1542/peds.5.5.783 ◽

1950 ◽

Vol 5 (5) ◽

pp. 783-790 ◽

Cited By ~ 1

Author(s):

JOHN D. CRAWFORD ◽

MARY E. TERRY ◽

G. MARGARET ROURKE

Keyword(s):

Surface Area ◽

Body Surface Area ◽

Body Surface ◽

Clinical Results ◽

Drug Dosage ◽

Common Denominator ◽

Dosage Calculation ◽

Patient Size ◽

One Year ◽

Relationship Of

Observations on the relationship of administered dosage per unit of body surface area and blood concentration achieved when different amounts of sulfadiazine and acetylsalicylic acid were given patients varying widely in size indicate that a direct proportionality exists for these two drugs regardless of patient size. On the basis of this finding body surface area was used as the common denominator in the calculation of dosages of a large variety of drugs for a period of more than one year on a service dealing with patients ranging from small prematures to young adults. The clinical results suggest that this method of dosage calculation offers the advantages of simplification and greater accuracy over calculations based on a unit of body mass or on the patient's age.

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Minimal model assessment of hepatic insulin extraction during an oral test from standard insulin kinetic parameters

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90842.2008 ◽

2009 ◽

Vol 297 (4) ◽

pp. E941-E948 ◽

Cited By ~ 32

Author(s):

M. Campioni ◽

G. Toffolo ◽

R. Basu ◽

R. A. Rizza ◽

C. Cobelli

Keyword(s):

Kinetic Parameters ◽

Surface Area ◽

Body Surface Area ◽

Body Surface ◽

Minimal Model ◽

Model Assessment ◽

C Peptide ◽

Insulin Kinetics ◽

Hepatic Insulin Extraction ◽

The Impact

In this article, a first aim was to develop a minimal modeling approach to noninvasively assess hepatic insulin extraction in 204 healthy subjects studied with a standard meal by coupling the already available meal C-peptide minimal model with a new insulin model. The ingredients of this model are posthepatic IDR, which in turn is described in terms of pancreatic ISR and hepatic insulin extraction HE, and a linear monocompartmental model of insulin kinetics. Even if ISR is provided by the C-peptide minimal model, the simultaneous assessment of HE and insulin kinetics is critical, since compensations may arise between parameters describing these two processes. Therefore, as a second aim of this study, a method was developed to predict standard values of insulin kinetic parameters in an individual on the basis of the individual's anthropometric characteristics. The statistical analysis, based on linear regression of insulin kinetic parameters estimated from IM-IVGTT data performed on the same subjects, demonstrated that insulin kinetic parameters can be accurately predicted from age and body surface area. Once kinetic parameters of the new insulin model were fixed to these values, HE profile and indexes during a meal were reliably estimated in each individual, indicating a significant suppression during the meal since the overall index of HE, equal to 60 ± 1% in the basal state, is reduced to 40 ± 1% during a meal. However, standard parameters provide an approximation of the individual one; thus, the third aim was to define the impact on estimated indexes of using standard instead of individually estimated values. Our results showed that the 25% uncertainty affecting as an average insulin kinetic parameters of an individual, when they are predicted from age and body surface area, translates into a similar relative uncertainty in the individual's hepatic insulin extraction indexes.

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Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation

Cell Transplantation ◽

10.1177/0963689719890596 ◽

2019 ◽

Vol 28 (1_suppl) ◽

pp. 25S-36S

Author(s):

Hongjun Wang ◽

Wenyu Gou ◽

Charlie Strange ◽

Jingjing Wang ◽

Paul J. Nietert ◽

...

Keyword(s):

Carbon Monoxide ◽

Cell Death ◽

Chronic Pancreatitis ◽

Adverse Events ◽

Total Pancreatectomy ◽

Insulin Independence ◽

Β Cell ◽

Post Transplantation ◽

Islet Autotransplantation ◽

Saturated Medium

Stresses encountered during human islet isolation lead to unavoidable β-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the study were randomized into carbon monoxide (islets harvested in a carbon monoxide-saturated medium) or control (islets harvested in a normal medium) groups. Islet yield, viability, oxygen consumption rate, β-cell death (measured by unmethylated insulin DNA), and serum cytokine levels were measured during the peri-transplantation period. Adverse events, metabolic phenotypes, and islet function were measured prior and at 6 months post-transplantation. No adverse events directly related to the infusion of carbon monoxide islets were observed. Carbon monoxide islets showed significantly higher viability before transplantation. Subjects receiving carbon monoxide islets had less β-cell death, decreased CCL23, and increased CXCL12 levels at 1 or 3 days post transplantation compared with controls. Three in 10 (30%) of the carbon monoxide subjects and none of the control subjects were insulin independent. This pilot trial showed for the first time that harvesting human islets in carbon monoxide-saturated solutions is safe for total pancreatectomy and islet autotransplantation patients.

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Prior surgery determines islet yield and insulin requirement after total pancreatectomy and islet autotransplantation

Pancreatology ◽

10.1016/j.pan.2012.12.346 ◽

2013 ◽

Vol 13 (2) ◽

pp. e83-e84

Author(s):

H. Wang ◽

K.D. Desai ◽

H. Dong ◽

S. Owzarski ◽

J. Romagnuolo ◽

...

Keyword(s):

Total Pancreatectomy ◽

Insulin Requirement ◽

Prior Surgery ◽

Islet Autotransplantation

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Immediate Postoperative Insulin Requirements May Predict Metabolic Outcome after Total Pancreatectomy and Islet Autotransplantation

Journal of Diabetes Research ◽

10.1155/2020/9282310 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Neha Verma ◽

Amer Rajab ◽

Jill Buss ◽

Luis Lara ◽

Kyle Porter ◽

...

Keyword(s):

Basal Insulin ◽

Cell Function ◽

Total Pancreatectomy ◽

Inverse Correlation ◽

Insulin Requirement ◽

Exocrine Function ◽

Long Term Outcome ◽

Insulin Requirements ◽

Islet Autotransplantation

Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Total pancreatectomy and islet autotransplantation (TPIAT) is a treatment option for patients with CP; however, predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield, and post-TPIAT glucose management data to further understand their relationship. Islet yield, glucose level, and insulin requirement for 72 hours postoperatively were collected for a total of 13 TPIAT recipients between 9-2013 and 9-2018. In addition, their glucose control and basal insulin requirements at 3, 6, and 12 months post-TPIAT were analyzed. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median postoperative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin, or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour postoperatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6, and 12 months showed a positive correlation. Despite the finding of inverse correlation of islet yield with long-term basal insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies. The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long-term insulin management following TPIAT. This observation may identify a high-risk group of patients in need of more intensive diabetes education and insulin treatment prior to hospital discharge.

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