| Title: | Birthweight, Type 2 Diabetes Mellitus, and Cardiovascular Disease |
| Journal: | Circulation Genomic and Precision Medicine |
| Published: | 6 Jun 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/29875125/ |
| DOI: | https://doi.org/10.1161/circgen.117.002054 |
| URL: | https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.117.002054 |
Publication 2793
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
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.</p>
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.</p>
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.</p>
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.</p>
18 Keywords
- Adult
- Aged
- Birth Weight
- Blood Glucose
- Blood Pressure
- Body Mass Index
- Cardiovascular Diseases
- Diabetes Mellitus, Type 2
- Female
- Genome-Wide Association Study
- Humans
- Incidence
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Observational Studies as Topic
- Risk Factors
- United States
6 Authors
- Daniela Zanetti
- Emmi Tikkanen
- Stefan Gustafsson
- James R. Priest
- Stephen Burgess
- Erik Ingelsson
1 Application
| Application ID | Title |
|---|---|
| 13721 | Causal associations of circulating biomarkers with cardiovascular disease |
Enabling scientific discoveries that improve human health