Abstract
BACKGROUND: Gestational diabetes mellitus (GDM) is linked with adverse health outcomes for both mother and infant and increases the risk of type 2 diabetes mellitus (T2DM) and long-term metabolic dysfunction postpartum. American Samoa experiences among the highest prevalence of GDM globally, with estimates suggesting 26-42% of women develop the condition. To date, no studies have attempted to understand the underlying etiology of GDM in Pacific Islanders or examine population-specific progression from GDM to T2DM. The GROW study will characterize glucose homeostasis, diabetes progression, and the impact of a Pacific-specific variant (rs373863828) in the CREBRF gene, which is known to protect against T2DM, on glucose metabolism during and after pregnancy. METHODS: We will establish a prospective cohort study of 350 pregnant women in American Samoa, enrolled in their first trimester and followed through 18 months postpartum. Participants will be genotyped for CREBRF rs373863828 and undergo frequently-sampled oral glucose tolerance test (fs-OGTTs), glycated hemoglobin (HbA1c), and continuous glucose monitoring (CGM) measurements to identify glycemic patterns across the perinatal period. Participants will complete questionnaires assessing reproductive health history, diet, physical activity, sleep, and psychosocial health. We will examine associations between CREBRF genotype and glucose homeostasis across pregnancy and postpartum and evaluate risk of GDM and subsequent T2DM. We will also explore associations between CREBRF genotype, changes in insulin secretion in pregnancy, and risk of adverse birth outcomes. DISCUSSION: Findings from this study are expected to inform precision medicine approaches to diabetes prevention, refine public health policies and clinical guidelines, and support community-based interventions aimed at reducing GDM and T2DM among Pacific Islander women and more broadly.