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1型糖尿病患者血管健康与卵巢衰老之间的关联

Association between vascular health and ovarian ageing in type 1 diabetes mellitus.

作者信息

Yarde F, Spiering W, Franx A, Visseren F L J, Eijkemans M J C, de Valk H W, Broekmans F J M

机构信息

Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands

Department of Vascular Medicine, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.

出版信息

Hum Reprod. 2016 Jun;31(6):1354-62. doi: 10.1093/humrep/dew063. Epub 2016 Apr 6.

Abstract

STUDY QUESTION

Is vascular health associated with ovarian reserve status using type 1 diabetes mellitus (DM-1) as a model for vascular compromise?

SUMMARY ANSWER

No conclusive evidence for an association between vascular health and ovarian ageing was found in women with DM-1.

WHAT IS KNOWN ALREADY

The mechanism behind advanced ovarian ageing has not yet been elucidated. We hypothesize that vascular impairment precedes ovarian ageing. DM-1 is hallmarked by premature vascular complications that may consequently play a role in the rate of primordial follicle decline.

STUDY DESIGN, SIZE, DURATION: A cross-sectional, patient-control study was performed in 150 premenopausal, regular cycling women with DM-1, as well as a reference population of 177 healthy, fertile women.

PARTICIPANTS/MATERIALS, SETTING, METHODS: In a single-study visit, an inventory of both ovarian reserve and vascular status was carried out in the DM-1 group. A transvaginal ultrasound to calculate the antral follicle count (AFC) and blood sampling for anti-Müllerian hormone (AMH), lipids, C-reactive protein and HbA1c measurements were performed. Furthermore, vascular screening including measurements of blood pressure, flow-mediated dilation, peripheral arterial tonometry, pulse wave velocity, pulse wave analysis and intima-media thickness was carried out. The relative decrease in serum AMH levels in women with DM-1 compared with healthy references was investigated.

MAIN RESULTS AND THE ROLE OF CHANCE

Systolic blood pressure was negatively correlated with both serum AMH (P= 0.006) and AFC (P= 0.004) in the DM-1 group. A non-linear relationship between HDL-cholesterol and serum AMH was found (P= 0.0001). No associations were detected between other vascular risk factors or vascular function tests and serum AMH or AFC in women with DM-1. With regard to the comparison of AMH levels between women with and without DM-1, mean AMH levels were 2.5 ± 1.9 ng/ml and 3.0 ± 2.8 ng/ml, respectively. After adjustment for confounders the difference in AMH levels between both groups appeared non-significant (fold change: 0.92, 95% confidence interval: 0.68-1.23).

LIMITATIONS, REASON FOR CAUTION: The use of different AMH assays and the cross-sectional design may limit the interpretation of this study.

WIDER IMPLICATIONS OF THE FINDINGS

The lack of evident association between vascular health and ovarian ageing may be the result of an insufficient vascular compromise in the relatively young, DM-1 group.

STUDY FUNDING/COMPETING INTERESTS: No external funding was received for conducting or publishing this study. F.Y., W.S., A.F., F.L.J.V., M.J.C.E. and H.W.d.V. have nothing to disclose. F.J.M.B. has received fees and grant support from the following companies: Ferring, Gedeon Richter, Merck Serono, Medical Specialties Distributors and Roche.

TRIAL REGISTRATION NUMBER

Not applicable.

摘要

研究问题

以1型糖尿病(DM - 1)作为血管受损模型,血管健康与卵巢储备状态是否相关?

总结答案

在患有DM - 1的女性中,未发现血管健康与卵巢衰老之间存在关联的确凿证据。

已知信息

卵巢早衰背后的机制尚未阐明。我们假设血管损伤先于卵巢衰老。DM - 1的特征是血管并发症过早出现,这可能因此在原始卵泡减少速率中起作用。

研究设计、规模、持续时间:对150名绝经前、月经周期规律的DM - 1女性以及177名健康、可育女性的对照人群进行了一项横断面病例对照研究。

参与者/材料、设置、方法:在单次研究访视中,对DM - 1组进行了卵巢储备和血管状态的评估。进行经阴道超声检查以计算窦卵泡计数(AFC),并采集血样检测抗苗勒管激素(AMH)、血脂、C反应蛋白和糖化血红蛋白(HbA1c)。此外,进行了血管筛查,包括测量血压、血流介导的血管舒张、外周动脉张力测定、脉搏波速度、脉搏波分析和内膜中层厚度。研究了DM - 1女性与健康对照相比血清AMH水平的相对下降情况。

主要结果及偶然性的作用

在DM - 1组中,收缩压与血清AMH(P = 0.006)和AFC(P = 0.004)均呈负相关。发现高密度脂蛋白胆固醇与血清AMH之间存在非线性关系(P = 0.0001)。在患有DM - 1的女性中,未检测到其他血管危险因素或血管功能测试与血清AMH或AFC之间存在关联。关于有和没有DM - 1的女性之间AMH水平的比较,平均AMH水平分别为2.5±1.9 ng/ml和3.0±2.8 ng/ml。在对混杂因素进行调整后,两组之间AMH水平的差异似乎无统计学意义(变化倍数:0.92,95%置信区间:0.68 - 1.23)。

局限性、谨慎原因:使用不同的AMH检测方法和横断面设计可能会限制本研究的解释。

研究结果的更广泛影响

血管健康与卵巢衰老之间缺乏明显关联可能是由于相对年轻的DM - 1组中血管受损不足所致。

研究资金/利益冲突:进行或发表本研究未获得外部资金。F.Y.、W.S. A.F.、F.L.J.V.、M.J.C.E.和H.W.d.V.无利益冲突需要披露。F.J.M.B.已从以下公司获得费用和资助支持:辉凌、吉德昂·里奇特、默克雪兰诺、医学专业分销商和罗氏。

试验注册号

不适用。

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