Freathy Rachel M
Institute of Biomedical and Clinical Science, University of Exeter Medical School, The Research, Innovation, Learning and Development (RILD) building, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
Diabetologia. 2016 Sep;59(9):1850-4. doi: 10.1007/s00125-016-4057-6. Epub 2016 Jul 19.
Lower birthweight is consistently associated with a higher risk of type 2 diabetes in observational studies, but the mechanisms underlying this association are not fully understood. Animal models and studies of famine-exposed populations have provided support for the developmental origins hypothesis, under which exposure to poor intrauterine nutrition results in reduced fetal growth and also contributes to the developmental programming of later type 2 diabetes risk. However, testing this hypothesis is difficult in human studies and studies aiming to do so are mostly observational and have limited scope for causal inference due to the presence of confounding factors. In this issue of Diabetologia, Wang et al (doi: 10.1007/s00125-016-4019-z ) have used genetic variation associated with birthweight in a Mendelian randomisation analysis to assess evidence of a causal link between fetal growth and type 2 diabetes. Mendelian randomisation offers the potential to examine associations between exposures and outcomes in the absence of factors that would normally confound observational studies. This commentary discusses the results of the Mendelian randomisation study carried out by Wang et al, in relation to the study design and its limitations. Challenges and opportunities for future studies are also outlined.
在观察性研究中，低出生体重一直与2型糖尿病的较高风险相关，但这种关联背后的机制尚未完全明确。动物模型以及对经历过饥荒人群的研究为发育起源假说提供了支持，该假说认为，子宫内营养状况不佳会导致胎儿生长受限，还会促使后期患2型糖尿病风险的发育编程。然而，在人体研究中验证这一假说存在困难，并且由于存在混杂因素，旨在进行此类验证的研究大多为观察性研究，因果推断的范围有限。在本期《糖尿病学》杂志中，Wang等人（doi: 10.1007/s00125-016-4019-z）在一项孟德尔随机化分析中利用与出生体重相关的基因变异，来评估胎儿生长与2型糖尿病之间因果关系的证据。孟德尔随机化有可能在不存在通常会混淆观察性研究的因素的情况下，检验暴露因素与结局之间的关联。本述评讨论了Wang等人开展的孟德尔随机化研究结果，涉及研究设计及其局限性。同时也概述了未来研究面临的挑战和机遇。
