Date of Award

Fall 2011

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Nursing

First Advisor

Terri H. Lipman

Second Advisor

Charlene W. Compher

Third Advisor

Nancy C. Tkacs

Abstract

Background: Vitamin D deficiency is markedly prevalent in children and adolescents with type 1 diabetes mellitus (T1DM). Despite accumulating evidence to support the link between vitamin D deficiency and both impaired glucose metabolism and altered immune responses in vitro and in vivo, it is not known whether vitamin D deficiency is linked to poor glycemic control and/or systemic levels of inflammatory cytokines in children and adolescents with T1DM. Aims: The purpose of this study was to examine the relationship between 25-hydroxyvitamin D (the functional indicator of vitamin D status) and HbA1c (the standardized index of glycemic control); and to determine whether inflammatory cytokines IL-6, IL-8, and IL-10 mediate this relationship in metabolically stable children and adolescents with T1DM. Methods: A cross-sectional design was used to examine these relationships in a convenience sample of 197 children and adolescents with T1DM 7-18 years, recruited from the Diabetes Center for Children at the Children’s Hospital of Philadelphia. Non-fasting serum levels of 25-hydroxyvitamin D, IL-6, IL-8, IL-10, and blood glucose were measured. Data on socio-demographic and disease-related variables including HbA1c were abstracted from medical records. Age- and sex-specific body mass index standard deviation scores (BMI z-score) were calculated. General linear modeling was used to examine the hypothesized relationships between primary variables, while controlling for select socio-demographic and disease-related covariates. Results: Mean HbA1c was 8.6±1.4%; 22.8% subjects had poor glycemic control. Mean 25-hydroxyvitamin D was 54.6±17.8nmol/L; 90.0% subjects had 25-hydroxyvitamin D levels less than 75nmol/L. Mean serum IL-6 was highest in overweight/obese adolescent females (1.57±1.29pg/ml). Mean serum IL-10 was highest in African Americans with poor glycemic control (15.2±22.5pg/ml). Serum levels of IL-8 were not detected in this sample. 25-hydroxyvitamin D was not associated with HbA1c (β=0.008; P=0.108), nor with IL-6 (β=-0.005; P=0.175) or IL-10 (β=0.004; P=0.356). IL-6 was not associated with HbA1c (β=0.09; P=0.418). IL-10 was significantly associated with HbA1c (β=0.21; P=0.008). Conclusions: In this study sample of metabolically stable children and adolescents with T1DM, neither 25-hydroxyvitamin D nor IL-6 were significantly associated with HbA1c. IL-10 was significantly associated with HbA1c. Clinical controlled trials are needed to confirm these results and assess the effect of varied doses of vitamin D supplements on inflammatory cytokines and ultimately measure the effect of inflammatory cytokines on HbA1c in T1DM.

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