Impact of intrauterine exposure to diabetes and social determinants of health on offspring cardiovascular disease risk in youth and early adulthood
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Diabetes is a highly prevalent complication of pregnancy with rates surpassing 15% in high-risk populations. The Developmental Origins of Health and Disease theory suggests the risk for many non-communicable chronic diseases might originate in utero. Indeed, more than 100 000 Canadian infants are exposed to diabetes in utero annually and subsequently have a higher risk for type 2 diabetes and obesity early in life. These conditions correlate tightly with cardiovascular diseases and may share common origins related to intrauterine diabetes exposure. Animal experiments support this theory by reporting worse cardiometabolic markers in pups exposed to diabetes in utero. This relationship has not been fully explored in humans, and it is not clear if it is modifiable. This thesis attempts to address these knowledge gaps with four unique studies: 1) a cross-sectional clinical study on the effect of intrauterine diabetes exposure on left ventricular structure and function, in a cohort of youth with type 2 diabetes; 2) a prospective population-based cohort study of intrauterine diabetes exposure and cardiovascular risk; 3) a prospective population-based cohort study on the role of high school completion and breastfeeding initiation in attenuating the association between intrauterine diabetes exposure and cardiovascular risk; and 4) a systematic review and meta-analysis of trials investigating intensive management of gestational hyperglycemia to prevent childhood obesity, a major facet of cardiometabolic risk. Results show that while left ventricular structure and function measured in adolescents is not different according to intrauterine diabetes exposure, youth and young adults exposed to diabetes in utero are 2-3 times more likely to receive a cardiovascular disease-related diagnosis compared to those not exposed, after adjustment for potential confounders such as birth weight for gestational age and socioeconomic status. Conversely, offspring exposed to diabetes who completed high school were 35% less likely to develop such diagnosis compared to those who did not complete high school. Breastfeeding initiation was not associated with cardiovascular risk. Finally, based on the limited existing evidence, managing hyperglycemia in pregnancy does not reduce childhood obesity. Together, these studies suggest intrauterine diabetes exposure as an independent but modifiable risk factor for cardiovascular disease in youth.