Early mechanisms of diabetes development in pediatric pancreatitis: A pilot study
Maria Graciela Parra Villasmil1, Melena Bellin2, Catherina Pinnaro1,3
1Department of Pediatrics, Stead Family Children's Hospital, University of Iowa, Iowa City, Iowa, USA.
Insights
Children with pancreatitis often develop diabetes. This pilot study found 35% of pediatric pancreatitis patients had dysglycemia, linked to insulin resistance and altered hormone levels.
Area of Science:
- Pediatric Gastroenterology
- Endocrinology
- Metabolic Research
Background:
- Approximately 9% of children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP) develop pancreatogenic diabetes, with a lifetime risk nearing 50%.
- Limited data exists on the pathophysiology and risk biomarkers for diabetes in pediatric pancreatitis.
- This pilot study aimed to investigate glycemic physiology in children diagnosed with ARP or CP.
Purpose of the Study:
- To investigate the glycemic physiology in children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP).
- To identify potential biomarkers and pathophysiological mechanisms associated with dysglycemia in this population.
Main Methods:
- Enrolled children (5-21 years) with CP or ARP diagnoses from the INSPPIRE-2 study.
- Utilized mixed meal tolerance testing (MMTT) to measure glucose, insulin, C-peptide, glucagon, GLP-1, and PP.
- Assessed hemoglobin A1c, continuous glucose monitoring (CGM), HLA haplotype, and diabetes autoantibodies; dysglycemia defined by fasting glucose ≥100 mg/dL or HbA1c ≥5.7%.
Main Results:
- Seven out of 20 participants (35%) exhibited dysglycemia, with one case of previously unrecognized diabetes.
- Individuals with dysglycemia showed increased insulin resistance, lower glucagon-like peptide-1 (GLP-1), and trends toward lower insulin and C-peptide levels.
- A trend towards higher pancreatic polypeptide (PP) levels was observed in participants with dysglycemia.
Conclusions:
- A significant proportion (35%) of children with pancreatitis in this pilot study presented with dysglycemia.
- Dysglycemia in pediatric pancreatitis may be mechanistically linked to insulin resistance.
- Other associated factors included impaired insulin secretion, reduced GLP-1, and elevated PP levels.
Objectives:
Approximately 9% of children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP) have pancreatogenic diabetes during childhood; lifetime risk approaches 50%. To date, data are limited on pathophysiology and biomarkers identifying those at highest risk. This pilot study investigated glycemic physiology in children with ARP or CP.
Methods:
Children (5-21 years) with an established diagnosis of CP or ARP, and participants of INSPPIRE-2 (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE) were enrolled. Mixed meal tolerance testing (MMTT) measured glucose, insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1) and pancreatic polypeptide (PP) at -5, -1, 0, 30, 60, 90, 120 min before/after a Boost HP beverage. Other measures included hemoglobin A1c, continuous glucose monitoring (CGM, Dexcom Pro), HLA haplotype, and diabetes autoantibodies. Glycemic variability metrics were calculated using "cgmanalysis." Dysglycemia was defined by fasting glucose ≥100 mg/dL or HbA1c ≥ 5.7%.
Results:
Twenty participants were enrolled (mean age 16.3 years; 65% female, 60% non-Hispanic white, 2 with pre-existing diabetes). Mean HbA1c was 5.7% (range 5.0-8.9); 7/20 had dysglycemia, 1 with previously unrecognized diabetes. Those with dysglycemia differed from normoglycemic participants by having greater insulin resistance, lower GLP-1, and trend toward lower insulin and C-peptide but higher PP on MMTT.
Conclusions:
In this small study, 35% of children with pancreatitis had dysglycemia, which may be mechanistically related to insulin resistance. Other trends associated with dysglycemia included impaired insulin secretion, reduced GLP-1, and unexpectedly elevated PP.
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