Abstract
Background:
Low adiponectin levels are associated with higher insulin resistance, development of type 2 diabetes, and increased adiposity in adults, but the evidence is more limited in youth. This study aimed to assess adiponectin as a biomarker of adverse metabolic health in youth and to examine whether cord blood DNA methylation (cbDNAm) is associated with child adiponectin levels.
Methods:
Participants from the Hyperglycemia and Adverse Pregnancy Outcome Study and Follow-up Study were included based on availability of cbDNAm, child anthropometry, adiponectin levels, and glucose OGTT measures (N=2,265) collected at mean age 11.4 ± 1.2 years. Cross-sectional associations between child log-transformed adiponectin and child adiposity and glycemic measures were evaluated via partial correlation. Linear regression models were used for epigenome wide analysis of cbDNAm and child adiponectin levels.
Results:
Lower child adiponectin levels were correlated with higher adiposity/dysglycemia outcomes (sum of skinfolds r= -0.285 and glucose sum of z-scores r= -0.070) as well as lower Matsuda (r= 0.135) and disposition indices (r= 0.062). cbDNAm at cg02713721, located in the CDH13 locus, was associated with child adiponectin levels (Bonferroni-adjusted p=0.01).
Conclusion:
The association of lower child adiponectin levels and higher child adiposity, glucose, and insulin resistance in a large cohort of healthy children provides evidence of adiponectin as a biomarker of adverse metabolic health in youth. DNA cord blood methylation at CpG 02713721 in CDH13, a gene involved in glucose regulation, was associated with child adiponectin levels suggesting a contribution to programming of future metabolic health.