Marott Sarah C W, Nordestgaard Børge G, Tybjærg-Hansen Anne, Benn Marianne
Department of Clinical Biochemistry (S.C.W.M., M.B.), Herlev and Gentofte Hospital, 2900 Hellerup, Denmark; Department of Clinical Biochemistry (B.G.N.), Herlev and Gentofte Hospital, and The Copenhagen General Population Study (S.C.W.M., B.G.N., A.T.-H., M.B.), Herlev and Gentofte Hospital, 2730 Herlev, Denmark; Department of Clinical Biochemistry (A.T.-H.), Rigshospitalet, 2100 Copenhagen Ø, Denmark; and Copenhagen University Hospital (S.C.W.M., B.G.N., A.T.-H., M.B.), Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark.
J Clin Endocrinol Metab. 2016 Aug;101(8):3212-21. doi: 10.1210/jc.2015-3777. Epub 2016 Jun 10.
The metabolic syndrome (MetS) is associated with type 2 diabetes (T2D). However, whether each of the 5 components of the MetS individually is causally associated with T2D is unknown.
We tested the hypothesis that each component is causally associated with T2D.
Mendelian randomization using genetic variations that alter levels of the MetS components are randomly assorted at gamete formation and free of confounding and reverse causation, which allows us to infer causality.
General community.
A total of 95 756 individuals from the prospective Copenhagen General Population Study.
Type 2 diabetes.
A 1-cm larger waist circumference was associated with an observational 5% (95% confidence interval, 4%-5%) and a causal genetic 5% (1%-10%) higher risk of T2D. In contrast, although a 1-unit higher level of triglycerides and blood pressure and a 1-unit lower level of high-density lipoprotein cholesterol were associated with higher observational T2D risk, the corresponding causal genetic risks were not. As expected, a 1 mmol/L higher glucose level was associated with an observational 32% (30%-34%) and a causal genetic 82% (21%-173%) higher T2D risk.
In conclusion, larger waist circumference and higher glucose levels were each causally associated with higher risk of T2D. Findings like these may change clinical thinking so that waist circumference control will be prioritized to the same extend as control of blood pressure, lipids, and glucose levels in T2D prevention.
代谢综合征（MetS）与2型糖尿病（T2D）相关。然而，MetS的5个组成成分各自是否与T2D存在因果关系尚不清楚。
我们检验了每个组成成分都与T2D存在因果关系的假设。
利用在配子形成时随机分配且无混杂因素和反向因果关系的基因变异进行孟德尔随机化，这使我们能够推断因果关系。
普通社区。
来自前瞻性哥本哈根普通人群研究的总共95756人。
2型糖尿病。
腰围每增加1厘米，观察到的2型糖尿病风险高5%（95%置信区间，4%-5%），因果性基因导致的风险高5%（1%-10%）。相比之下，虽然甘油三酯和血压水平每升高1个单位以及高密度脂蛋白胆固醇水平每降低1个单位与观察到的2型糖尿病风险升高相关，但相应的因果性基因风险却并非如此。正如预期的那样，血糖水平每升高1 mmol/L，观察到的2型糖尿病风险高32%（30%-34%），因果性基因导致的风险高82%（21%-173%）。
总之，腰围增加和血糖水平升高均与2型糖尿病风险升高存在因果关系。此类发现可能会改变临床思维，从而在2型糖尿病预防中，腰围控制将与血压、血脂和血糖水平控制被同等重视。
