Epigenetic Programming of Offspring Cardiometabolic Risk by Gestational Diabetes Mellitus in Nigerian Pregnancies: A Mechanistic Cohort Study

Gestational diabetes mellitus (GDM) programmes offspring cardiometabolic risk through mechanisms increasingly attributed to epigenetic modification of foetal gene expression, yet this mechanistic pathway has not been investigated in any African population where the GDM-offspring risk relationship may be modified by distinct dietary, ethnic, and environmental exposures. This dissertation investigates epigenetic programming of offspring cardiometabolic risk by GDM in Nigerian pregnancies. A prospective cohort recruited 100 GDM-affected and 100 normoglycaemic pregnancies at Federal Teaching Hospital Gombe, Aminu Kano Teaching Hospital, and University of Abuja Teaching Hospital. Cord blood and placental tissue were collected at delivery for genome-wide DNA methylation analysis using the Illumina EPIC array. Offspring were followed to 12 months for anthropometric and metabolic outcome assessment. Pathway-specific methylation analysis targeted IGF2, LEPR, PPARGC1A, and ADIPOQ loci. GDM pregnancies showed significant hypomethylation of IGF2 DMR0 and hypermethylation of ADIPOQ promoter in cord blood, consistent with foetal adipogenesis programming. Offspring of GDM mothers showed higher adiposity indices and insulin resistance markers at 12 months. Methylation of ADIPOQ promoter at birth predicted 12-month adiposity independently of neonatal birth weight. Maternal hyperglycaemia severity correlated dose-dependently with epigenetic effect magnitude. The dissertation provides the first GDM epigenetic programming dataset from West Africa and introduces original insights into population-specific metabolic risk programming mechanisms. Keywords: gestational diabetes mellitus, epigenetics, offspring cardiometabolic risk, DNA methylation, Nigeria