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阿片类药物依赖患者维生素D代谢的特征是什么?一项在澳大利亚初级保健机构开展的探索性纵向研究。

What are the characteristics of vitamin D metabolism in opioid dependence? An exploratory longitudinal study in Australian primary care.

作者信息

Reece Albert Stuart, Hulse Gary Kenneth

机构信息

Department of Psychiatry and Clinical Neurosciences, University of Western Australia, Brisbane, Queensland, Australia.

Department of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Queensland, Australia.

出版信息

BMJ Open. 2018 Jan 13;8(1):e016806. doi: 10.1136/bmjopen-2017-016806.

Abstract

OBJECTIVE

Compare vitamin D levels in opioid dependence and control population and adjust for relevant confounding effects. Nuclear hormone receptors (including the vitamin D receptor) have been shown to be key transducers and regulators of intracellular metabolism and comprise an important site of pathophysiological immune and metabolic dysregulation potentially contributing towards pro-ageing changes observed in opioid-dependent patients (ODPs).

DESIGN

Longitudinal prospective comparing ODPs with general medical controls (GMCs).

SETTING

Primary care.

PARTICIPANTS

Prospective review comparing 1168 ODP (72.5% men) and 415 GMC (51.6% men, p<0.0001). Mean ages were 33.92±0.31 (mean±SEM) and 41.22±1.32 years, respectively (p<0.0001). Opioid use in the ODP has been previously reported and shown to be typical.

INTERVENTIONS

Nil. Observational study only.

PRIMARY AND SECONDARY OUTCOMES

Serum vitamin D levels and relevant biochemical parameters.

RESULTS

Vitamin D levels were higher in the ODP (70.35±1.16 and 57.06±1.81 nmol/L, p<0.0001). The difference in ages between the two groups was handled in an age-matched casecontrol subanalysis and also by multiple regression. Sexes were analysed separately. The age:status (or age:time:status) was significant in casecontrol, cross-sectional and longitudinal analyses in both sexes (p<0.05). Modelled vitamin D was 62.71 vs 57.81 nmol/L in the two groups. Time-dependent mixed-effects models quadratic in age outperformed linear-only models (p=0.0377). ODP vitamin D was shown to vary with age and to correlate with alanine aminotransferase establishing it as a biomarker of age in this group. Hepatitis C seronegativity was significant in regression models (from p=0.0015).

CONCLUSION

Vitamin D was higher in ODP in both sexes in bivariate, cross-sectional, casecontrol and longitudinal analyses and was robust to the inclusion of metabolic and immune biomarkers. That Hepatitis C seronegativity was significant suggests opioid dependence has an effect beyond simply that of its associated hepatitides. This finding may relate to the accelerated ageing process previously described in opioid dependence.

摘要

目的

比较阿片类药物依赖人群与对照人群的维生素D水平,并对相关混杂效应进行校正。核激素受体(包括维生素D受体)已被证明是细胞内代谢的关键转导器和调节因子,是病理生理免疫和代谢失调的重要位点,可能导致阿片类药物依赖患者(ODP)出现促衰老变化。

设计

将ODP与普通医疗对照(GMC)进行纵向前瞻性比较。

设置

初级保健。

参与者

前瞻性回顾比较了1168名ODP(72.5%为男性)和415名GMC(51.6%为男性,p<0.0001)。平均年龄分别为33.92±0.31(均值±标准误)岁和41.22±1.32岁(p<0.0001)。先前已报道ODP中的阿片类药物使用情况,并显示为典型情况。

干预措施

无。仅为观察性研究。

主要和次要结果

血清维生素D水平及相关生化参数。

结果

ODP的维生素D水平较高(分别为70.35±1.16和57.06±1.81nmol/L,p<0.0001)。两组之间的年龄差异在年龄匹配的病例对照亚分析以及多元回归中进行了处理。对性别分别进行了分析。年龄:状态(或年龄:时间:状态)在两性的病例对照、横断面和纵向分析中均具有显著性(p<0.05)。两组中模拟的维生素D水平分别为62.71和57.81nmol/L。年龄呈二次方的时间依赖性混合效应模型优于仅呈线性的模型(p=0.0377)。ODP的维生素D水平显示随年龄变化,并与丙氨酸转氨酶相关,表明其在该组中是年龄的生物标志物。丙型肝炎血清阴性在回归模型中具有显著性(p值从0.0015起)。

结论

在双变量、横断面、病例对照和纵向分析中,两性ODP的维生素D水平均较高,并且在纳入代谢和免疫生物标志物后依然显著。丙型肝炎血清阴性具有显著性,这表明阿片类药物依赖的影响不仅仅局限于其相关的肝炎。这一发现可能与先前描述的阿片类药物依赖中的加速衰老过程有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d23d/5780717/1cd8c8399fac/bmjopen-2017-016806f01.jpg

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