Birthweight, Type 2 Diabetes Mellitus, and Cardiovascular Disease

Abstract

BACKGROUND: Low birthweight has been associated with a higher risk of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease. The Barker hypothesis posits that intrauterine growth restriction resulting in lower birthweight is causal for these diseases, but causality is difficult to infer from observational studies. METHODS: We performed regression analyses to assess associations of birthweight with cardiovascular disease and T2D in 237 631 individuals from the UK Biobank. Further, we assessed the causal relationship of such associations using Mendelian randomization. RESULTS: In the observational analyses, birthweight showed inverse associations with systolic and diastolic blood pressure (β, −0.83 and −0.26; per raw unit in outcomes and SD change in birthweight; 95% confidence interval [CI], −0.90 to −0.75 and −0.31 to −0.22, respectively), T2D (odds ratio, 0.83; 95% CI, 0.79−0.87), lipid-lowering treatment (odds ratio, 0.84; 95% CI, 0.81−0.86), and coronary artery disease (hazard ratio, 0.85; 95% CI, 0.78−0.94), whereas the associations with adult body mass index and body fat (β, 0.04 and 0.02; per SD change in outcomes and birthweight; 95% CI, 0.03−0.04 and 0.01−0.02, respectively) were positive. The Mendelian randomization analyses indicated inverse causal associations of birthweight with low-density lipoprotein cholesterol, 2-hour glucose, coronary artery disease, and T2D and positive causal association with body mass index but no associations with blood pressure. CONCLUSIONS: Our study indicates that lower birthweight, used as a proxy for intrauterine growth retardation, is causally related with increased susceptibility to coronary artery disease and T2D. This causal relationship is not mediated by adult obesity or hypertension.

Substantial Cardiovascular Morbidity in Adults With Lower-Complexity Congenital Heart Disease

“…In this study, the elevated risk of ACS and ischemic stroke associated with ACHD despite adjustment for atherosclerotic risk factors suggests a non-atherosclerotic etiology of cardiovascular disease. The development of cardiovascular disease may be related to a number of other factors including surgical interventions 34 , physiological stressors of early life 35 , intrinsic cellular dysfunction, and genetic predisposition 30 . Risk for ischemic stroke and AF have previously been associated with septal defects (with or without closure) and palliative shunt procedures 4,28,36 , suggesting a cardioembolic rather than atherosclerotic mechanism.…”

Bisphenol A and Phthalates in Diet: An Emerging Link with Pregnancy Complications

“…Low birth weight is a well-known risk factor for obesity and T2D [113]. Interestingly, EDCs are reported to affect foetal growth and the length of pregnancy in cohort studies.…”

Mendelian randomization study of maternal influences on birthweight and future cardiometabolic risk in the HUNT cohort

“…Mendelian randomization (MR) is an epidemiological method used to investigate whether an observational association between an exposure and an outcome represents a causal relationship 10 . Several studies have recently attempted to use MR to investigate the relationship between lower birthweight and cardiometabolic disease to inform on the validity of DOHaD 11 – 13 . However, these MR studies have used sub-optimal methodologies in which only offspring genotypes are considered as genetic instruments to proxy offspring birthweight 14 .…”