title: Autologous umbilical cord blood infusion followed by oral docosahexaenoic acid and vitamin D supplementation for C-peptide preservation in children with Type 1 diabetes.
abstract: We sought to determine if autologous umbilical cord blood (UCB) infusion followed by 1 year of supplementation with vitamin D and docosahexaenoic acid (DHA) can preserve C-peptide in children with type 1 diabetes. We conducted an open-label, 2:1 randomized study in which 15 type 1 diabetes subjects with stimulated C-peptide > .2 pmol/mL received either (1) autologous UCB infusion, 1 year of daily oral vitamin D (2000 IU), and DHA (38 mg/kg) and intensive diabetes management or (2) intensive diabetes management alone. Primary analyses were performed 1 year after UCB infusion. Treated (N = 10) and control (N = 5) subjects had median ages of 7.2 and 6.6 years, respectively. No severe adverse events were observed. Although the absolute rate of C-peptide decline was slower in treated versus control subjects, intergroup comparisons failed to reach significance (P = .29). Area under the curve C-peptide declined and insulin use increased in both groups (P < .01). Vitamin D levels remained stable in treated subjects but declined in control subjects (P = .01). DHA levels rose in treated subjects versus control subjects (P = .003). CD4/CD8 ratio remained stable in treated subjects but declined in control subjects (P = .03). No changes were seen in regulatory T cell frequency, total CD4 counts, or autoantibody titers. Autologous UCB infusion followed by daily supplementation with vitamin D and DHA was safe but failed to preserve C-peptide. Lack of significance may reflect small sample size. Future efforts will require expansion of specific immunoregulatory cell subsets, optimization of combined immunoregulatory and anti-inflammatory agents, and larger study cohorts.
authors.affiliation: Department of Pediatrics, the University of Florida, Gainesville, FL 32610, USA. hallemj@peds.ufl.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Haller
authors.forename: Clive H
authors.initials: CH
authors.lastname: Wasserfall
authors.forename: Maigan A
authors.initials: MA
authors.lastname: Hulme
authors.forename: Miriam
authors.initials: M
authors.lastname: Cintron
authors.forename: Todd M
authors.initials: TM
authors.lastname: Brusko
authors.forename: Keiran M
authors.initials: KM
authors.lastname: McGrail
authors.forename: John R
authors.initials: JR
authors.lastname: Wingard
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Theriaque
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ferguson
authors.forename: Marianne
authors.initials: M
authors.lastname: Kozuch
authors.forename: Michael
authors.initials: M
authors.lastname: Clare-Salzler
authors.forename: Mark A
authors.initials: MA
authors.lastname: Atkinson
authors.forename: Desmond A
authors.initials: DA
authors.lastname: Schatz
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D002096:C-Peptide / Q000097:blood*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D016176:T-Lymphocyte Subsets; D014182:Transplantation, Autologous; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D002096:C-Peptide; D014807:Vitamin D; D004281:Docosahexaenoic Acids