据观察，低水平的高密度脂蛋白胆固醇(HDL-C)与2行188bet在线平台网址 风险增加有一致的相关性。这暗示，增加血浆HDL-C水平可能是减少2型188bet在线平台网址 风险的新治疗选择。HDL-C水平是否是与2型188bet在线平台网址 相关的原因尚未知。因此，丹麦学者对上述问题进行了研究，结果表明，从基因方面减少HDL-C水平不增加2型188bet在线平台网址 风险。相关论文近期在线发表于《188bet在线平台网址 》(Diabetes)杂志。

        该前瞻性研究共纳入了47627例一般人群，检测HDL-C相关的基因变异是否与低水平的HDL-C水平以及2型188bet在线平台网址 风险增加有关。与HDL-C基因得分降低和等位基因数量减少相关的HDL-C水平分别减少13%和20%。相应地2型188bet在线平台网址 理论预测危险比为分别1.44和1.77，但遗传评估不具显著性。

        与相应观察性危险比值1.37相比，基因得分和等位基因数量下降的情况下，相应HDL-C水平减少0.2 mmol/L的2型188bet在线平台网址 遗传风险比值分别为0.91和0.93。

        参考文献：Christiane L. Haase,et al. Diabetes . Published online before print May 13, 2015, doi:10.2337/db14-1603

High-density lipoprotein cholesterol and risk of type 2 diabetes: a Mendelian randomization study
1. Christiane L. Haase, PhD1,
2. Anne Tybjærg-Hansen, MD DMSc1,2,3,
3. Børge G. Nordestgaard, MD DMSc2,3,4 and
4. Ruth Frikke-Schmidt, MD DMSc1,3⇑
+Author Affiliations
1. 1Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
2. 2The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospitals and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
3. 3The Copenhagen General Population Study and Copenhagen University Hospitals and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
4. 4The Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospitals and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
1. Corresponding Author: Ruth Frikke-Schmidt: E-mail: ruth.frikke-schmidt@regionh.dk
Abstract
Observationally, low levels of high-density-lipoprotein (HDL) cholesterol are consistently associated with increased risk of type 2 diabetes. Therefore, plasma HDL cholesterol increasing has been suggested as a novel therapeutic option to reduce risk of type 2 diabetes. Whether levels of HDL cholesterol are causally associated with type 2 diabetes is unknown.
In a prospective study of the general population (N=47,627), we tested whether HDL cholesterol related genetic variants were associated with low HDL cholesterol levels and, in turn, with an increased risk of type 2 diabetes. HDL cholesterol decreasing gene scores and allele numbers associated with up to -13% and -20% reductions in HDL cholesterol levels. The corresponding theoretically predicted hazard ratios for type 2 diabetes were 1.44 (95% confidence interval: 1.38-1.52) and 1.77 (1.61-1.95), while the genetic estimates were non-significant.
Genetic risk ratios for type 2 diabetes for a 0.2 mmol/L reduction in HDL cholesterol were 0.91 (0.75-1.09) and 0.93 (0.78-1.11) for HDL cholesterol decreasing gene scores and allele numbers, respectively, compared to the corresponding observational hazard ratio of 1.37 (1.32-1.42).
In conclusion, genetically reduced HDL cholesterol does not associate with increased risk of type 2 diabetes, suggesting that the corresponding observational association is due to confounding and/or reverse causation.