Early mechanisms of diabetes development in pediatric pancreatitis: A pilot study

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.