血尿酸与代谢性风险

越来越多研究表明,高血尿酸与代谢综合征密切相关。传统观点认为尿酸水平仅是代谢综合征的一个生物标志而不能预测代谢综合征,这种观点可能被修改。降低血尿酸可能是预防糖尿病及多种慢性疾病的一种新的治疗方法。     

儿童肥胖与代谢综合征相关性的研究进展

近年来,儿童肥胖的检出率呈逐年增长趋势,代谢综合征是以糖代谢异常、血脂异常、高血压、中心性肥胖等集聚于一体的症候群。儿童肥胖是儿童代谢综合征发生的中心因素,严重影响儿童的身心健康,应及早诊断及治疗,而控制儿童肥胖的发生和发展是预防代谢综合征,降低成人心血管疾病、糖尿病等发病率的重要因素。治疗上重在预防,建议合理饮食、加强锻炼,阻止儿童肥胖及代谢综合征的流行与发展。本文针对儿童肥胖与代谢综合征相关性的研究进展进行综述,并提出进一步研究的设想。     

国外近五年关于阿尔茨海默病的研究进展

痴呆的患病率世界各地不尽相同。这可能是由于调查方法及诊断标准的差异性和人口老龄化的程度不同而造成的,也可能存在地区性。一般来说,社会经济与疾病因素,也增加了痴呆的患病率,如肥胖、糖尿病、高血压、血脂异常、代谢综合征等。因此调节这些因素成为了至关重要的社会公共问题。痴呆的患病率中,阿尔茨海默病为重要亚型,本文对阿尔茨海默病国外流行病学的调查及易感因素的研究综述如下。     

某部机关中老年干部代谢综合征现况调查

目的:了解某部机关中老年干部代谢综合征(Metabolic syndrome,MS)的患病情况,为该类人群疾病的防治提供依据。方法:收集2013年4~5月年在解放军第309医院体检的452例某部机关中老年干部查体资料,按2007年《中国成人血脂异常防治指南》提出的代谢综合征诊断标准进行诊断,分析代谢综合征及代谢指标异常患病情况。结果:受检人群MS患病率11.73%,男性高于女性(P0.05)。年龄组患病率以60~69岁组最高(23.08%)。单项代谢异常检出率从高至低依次为血脂异常(41.15%)、超重和/肥胖(38.5%)、血压升高(25.0%)和血糖升高(9.73%)。不同年龄组代谢指标异常分布情况不同。代谢异常类型以血压升高+血脂升高+超重/肥胖模式人数最多。除MS外,仍有34.52%的人群存在1-2种代谢指标异常。结论:MS可防可控,应注重以胰岛素抵抗(Insulin Resistance,IR)为靶点的多危险因素综合治疗。     

雄激素与代谢相关疾病的研究进展

雄激素可以广泛地影响机体的代谢功能,除了传统公认的促进蛋白质合成外,也可以促进脂质代谢、降低血糖并改善胰岛素抵抗.雄激素缺乏与多种代谢相关疾病的关系被逐渐重视,如代谢综合征、2型糖尿病以及相关的心血管疾病.目前的观点认为,睾酮水平较低的人群更易发生代谢综合征、2型糖尿病和/或心血管疾病.而临床数据也表明,前列腺癌患者接受雄激素剥夺治疗后更容易患上述疾病.雄激素替代治疗则能够不同程度缓解上述疾病的状况.对炎性因子、脂质合成、血管重构以及内皮细胞功能的影响有可能是雄激素参与机体代谢的途径.本文将对雄激素和代谢综合征、2型糖尿病、心血管疾病的关系进行综述.     

多囊卵巢综合征伴胰岛素抵抗的研究进展

多囊卵巢综合征（polycystic ovary syndrome,PCOS）是国内外研究者、医患人员非常关心的育龄期妇女常见的内分泌代谢疾病,其主要表现为闭经、月经量减少、肥胖、不孕、体多毛等。多数伴有胰岛素抵抗（insulin resistance,IR）的发生,胰岛素抵抗（insulin resistance,IR）是指正常水平的胰岛素促进葡萄糖摄取及利用能力下降,机体各组织、器官代偿性分泌胰岛素以维持机体血糖稳定的一种代谢状态。近年来的研究不断证实PCOS患者2型糖尿病、血脂代谢紊乱及代谢综合征（metabolicsyndrome,MS）等并发症的发病率明显增高。运动能够改善2型糖尿病患者胰岛素抵抗的说法已经得到了共识,其分子机制也逐渐分明。PCOS患者胰岛素抵抗的研究目前仍处于进一步探讨阶段,但是经过近几年的努力已经有了新的进展,若在PCOS胰岛素抵抗患者的治疗过程中给予一定的运动干预,相信一定能够有新的突破。本文就PCOS患者胰岛素抵抗研究的机制、诊断及治疗方法的新进展简单做一综述。     

线粒体自噬影响胰岛素抵抗的作用及机制

胰岛素抵抗（IR）是诱发许多代谢疾病的关键因素,包括代谢综合征、非酒精性脂肪性肝病、动脉粥样硬化和2型糖尿病（T2DM）。随着相关代谢疾病日益增多,寻找新的治疗靶点迫在眉睫。线粒体自噬是一种选择性自噬,其通过清除受损和功能失调的线粒体以维持正常线粒体功能和能量代谢。研究发现,线粒体自噬在代谢疾病中有积极作用,线粒体自噬受到各种信号通路与信号分子调控而改善代谢疾病,如AMPK/ULK1、PINK1/Parkin信号通路以及BNIP3/Nix和FUNDC1等信号分子。本文阐述了线粒体自噬在胰岛素抵抗中的作用及调控机制,综述了近年的相关研究进展。     

天然AMPK激活剂防治代谢综合征的研究进展

能量代谢紊乱是代谢综合征产生的根本原因。AMPK(AMP-activated protein kinase)作为细胞乃至整个机体的能量调节器在能量较低的状态下被激活,促进分解代谢,抑制合成代谢,从而恢复能量平衡状态。因此,AMPK有望成为防治代谢综合征的新型靶点。单纯的药物治疗代谢综合征难以达到理想效果,许多天然营养分子也具有激活AMPK的功效,提示营养干预可能成为缓解代谢综合征的另一种新型有效手段。     

非编码RNA在股骨头坏死发展中的作用及中药干预研究进展

非编码RNA(non-coding RNA, ncRNA)是一类从基因组中转录而来、对蛋白质编码有调节作用的RNA。研究证明, ncRNA对骨髓间充质干细胞分化、骨代谢和血管修复发挥调节作用,参与了股骨头坏死的发病进程,而近年来作为治疗手段之一,关于中药药物治疗疾病、影响ncRNA表达的实验也不在少数,相关研究对于股骨头坏死发生机制的确定、诊疗手段的丰富具有重要意义。该文通过对知网、PubMed数据库内的相关文献进行归纳,综述了近年来该领域的研究进展,将中药干预与之联系,为疾病的临床诊断、靶向治疗提供了新的理论依据和方向。     

慢性阻塞性肺疾病与代谢综合征及颈动脉内膜厚度的相关性研究

目的:研究慢性阻塞性肺疾病与代谢综合征及颈动脉内膜厚度的关系。方法:选择2014年8月至2015年4月在我院就诊的慢性阻塞性肺疾病患者60例作为研究组,另选择同期在我院接受健康体检的60名志愿者作为对照组。比较两组空腹血糖、甘油三酯及高密度脂蛋白胆固醇水平、代谢综合征的发生率、颈动脉内膜厚度以及合并与不合并代谢综合征的慢性阻塞性肺疾病患者的肺功能和颈动脉内膜厚度,并采用多元回归分析颈动脉内膜厚度与慢性阻塞性肺疾病及代谢综合征的相关性。结果:与对照组相比,研究组患者空腹血糖(FPG)明显升高,而甘油三酯(TG)水平明显降低,差异具有统计学意义(P0.05);两组高密度脂蛋白胆固醇(HDL-C)比较差异无统计学意义(P0.05)。研究组代谢综合征的发病率、颈动脉内膜厚度均明显高于对照组,差异具有统计学意义(P0.05);慢性阻塞性肺疾病合并代谢综合征患者的肺功能明显优于无代谢综合征的慢性阻塞性肺疾病患者,差异具有统计学意义(P0.05);合并代谢综合征的慢性阻塞性肺疾病患者FEV1占预计值百分比及FEV1/FVC均明显高于无代谢综合征慢性阻塞性肺疾病患者的对应值,差异具有统计学意义(P0.05)。Logistic回归分析结果显示慢性阻塞性肺疾病与颈动脉内膜厚度呈独立相关性,而代谢综合征与颈动脉内膜厚度无直接相关性。结论:慢性阻塞性肺疾病与颈动脉内膜厚度呈独立相关,且慢性阻塞性肺疾病合并代谢综合征患者发生颈动脉粥样硬化的风险更高。     

Association of Plasma Parathyroid Hormone with Metabolic Syndrome and Risk for Cardiovascular Disease

ObjectiveTo review the current literature investigating the association of plasma parathyroid hormone (PTH) with the prevalence of metabolic syndrome and the risk for cardiovascular disease (CVD).MethodsWe conducted a search of PubMed and Medline database using the terms hyperparathyroidism, metabolic syndrome, hypertension, hyperlipidemia, hyper-glycemia, and CVD. We reviewed relevant studies from 2004 to 2012.ResultsThe current literature assessing the association of plasma PTH levels with metabolic syndrome and CVD is inconsistent; however, positive associations among hyperparathyroidism, metabolic syndrome, and CVD were found in a majority of the studies. The differences in the study populations may partly explain the mixed results.ConclusionIn the general population, a high serum PTH level predisposes patients to CVD mortality. Further research is needed to determine the role of PTH in the etiology of metabolic syndrome and CVD. (Endocr Pract. 2013;19:712-717)     

肠道菌群与高血压病主要危险因素的相关性及 中药干预研究现状

近年来国内、外文献报道高血压病的发生可能与肠道菌群失调相关。肠道菌群与高血压病主要危险因素(肥胖、高血脂、糖尿病、代谢综合征、动脉粥样硬化)具有一定的相关性,某些益生菌或其发酵产品可能通过改善肠道菌群的方式为高血压病的治疗提供新的思路和途径。近年来研究显示中药具有较长的肠道停留时间,从而有利于其发挥调节肠道菌群的作用,提示某些中药具有调节肠道菌群的作用。但目前国内、外尚无关于中药直接通过肠道菌群作用而干预高血压病的文献报道,而近年来国内有研究显示肠道菌群可能是中药干预高血压病主要危险因素的作用机制之一。     

Duodenal Mucosa: A New Target for the Treatment of Type 2 Diabetes

ObjectiveAfter a high-fat and high-sugar diet, the duodenal mucosa of rodents proliferate and trigger the signal of insulin resistance, which may be the cause of type 2 diabetes (T2D). In response to this phenomenon, researchers have designed the duodenal mucosal resurfacing (DMR) procedure, mainly through the hydrothermal ablation procedure, to restore the normal mucosal surface, thereby correcting this abnormal metabolic signal. This article aims to understand the changes in duodenum before and after the onset or treatment of T2D, and the potential mechanisms of DMR procedure.MethodsA literature search of PubMed and Web of Science was conducted using appropriate keywords.ResultsBoth animal and clinical studies have shown that the villus thickness, intestinal cells, glucose transporters, enteric nerves, and gut microbiota and their metabolites in the duodenum undergo corresponding changes before and after the onset or treatment of T2D. These changes may be related to the pathogenesis of T2D. DMR procedure may produce beneficial glycemic and hepatic metabolic effects by regulating these changes.ConclusionThe duodenum is an important metabolic signaling center, and limiting nutrient exposure to this critical region will have powerful metabolic benefits. The DMR procedure may regulate glycemic and hepatic parameters through various mechanisms, which needs to be further confirmed by a large number of animal and clinical studies.     

Rationale for Leptin-Replacement Therapy for Severe Lipodystrophy

ObjectiveTo review evidence supporting the hypothesis that metabolic manifestations of lipodystrophy result from leptin deficiency and that leptin replacement may be a viable treatment for generalized lipodystrophy.MethodsThis review results from the authors’ collective clinical experience and a comprehensive MEDLINE search of the English-language literature (1998 to 2009) on “leptin and lipodystrophy.”ResultsSevere lipodystrophy syndromes are characterized by loss of subcutaneous adipose tissue and thus a relative deficiency of the adipocyte-secreted hormone leptin. Several small, nonrandomized, open-label trials in a composite total of more than 100 patients with severe lipodystrophy not related to human immunodeficiency virus infection have evaluated the efficacy and safety of recombinant human methionyl leptin (metreleptin) therapy. Variables observed to improve after treatment with metreleptin include glycemic control, insulin sensitivity, plasma triglycerides, caloric intake, liver volume and lipid content, intramyocellular lipid content, and neuroendocrine and immunologic end points. In these studies, metreleptin treatment was well tolerated. Typical daily replacement doses for metreleptin were 0.06 to 0.08 mg/kg for female patients and 0.04 mg/kg for male patients, administered by subcutaneous injection twice daily. Although metreleptin is not yet approved for routine clinical use, it is available by means of expanded access provisions for patients with severe lipodystrophy and associated metabolic abnormalities.ConclusionEvidence published in the medical literature indicates that treating severe lipodystrophy as a leptin deficiency syndrome can improve the metabolic outcomes in affected patients. (Endocr Pract. 2010;16:324-333)     

Intensive Metabolic Support : Evolution and Revolution

ObjectiveTo describe a new aspect of critical care termed intensive metabolic support.MethodsWe performed a MEDLINE search of the English-language literature published between 1995 and 2008 for studies regarding the metabolic stages of critical illness, intensive insulin treatment, and intensive metabolic support in the intensive care unit, and we summarize the clinical data.ResultsIntensive metabolic support is a 3-component model involving metabolic control and intensive insulin therapy, early nutrition support, and nutritional pharmacology aimed at preventing allostatic overload and the development of chronic critical illness. To improve clinical outcome and prevent mortality, intensive metabolic support should start on arrival to the intensive care unit and should end only when patients are in the recovery phase of their illness.ConclusionsIntensive metabolic support should be an essential part of the daily treatment strategy in critical care medicine. This will involve a newfound and extensive collaboration between the endocrinologist and the intensivist. We call for well-designed future studies involving implementation of this protocol to decrease the burden of chronic critical illness. (Endocr Pract. 2008;14:1047-1054)     

Discovery of quality-marker ingredients of Panax quinquefolius driven by high-throughput chinmedomics approach

BackgroundQuality control of traditional Chinese medicine (TCM) has always been a hot issue to TCM. However, due to the complexity of TCM ingredients, the current quality standards of TCM have problems that are difficult to guarantee clinical efficacy. American ginseng, the dried roots of Pawajc quinquefolium L. (Araliaceae), is a valuable herbal medicine due to various pharmacological effects and huge health benefit, which are associated with numerous active ingredients such as ginsenosides. Although a large number of studies have investigated the active ingredients of American ginseng, Q-markers reflecting comprehensive review on its efficacies has yet been unrevealed.PurposeThe study aims to discover the Q-markers of Panax quinquefolius (American ginseng), provides a powerful method to clarify the significant ingredents of TCM and help further discovering extensive quality evaluation model,contributing to a significant improvement of TCM quality standard.MethodsMice general status, biochemical indexes assay, urine metabolic profile, and serum metabolic profile were utilized for model replication and efficacy evaluation. The in vitro and in vivo constituents of American ginseng using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS) with Serum Pharmacochemistry of TCM were in-depth investigated. Q-markers that were associated with core markers of therapeutic effects were excavated by a plotting of correlation between marker metabolites and serum constituents (PCMS) approach.ResultsCorrelation analysis of 41 blood and urine labeled metabolites with 14 serum components showed that 24-methyl-7-cholesten-3β-ol, zizybeoside II, betulin, ginsenoside Rd, cinnamyl alcohol, pseudoginsenoside F11 is highly correlated with the therapeutic effects of Compound Zaofan Pill (CZP), while pseudoginsenoside F11 and ginsenoside Rd are highly correlated with the therapeutic effects of American ginseng. The six absorbed blood compounds can be considered as potential Q-markers for compound, of which two compounds, such as pseudoginsenoside F11 and ginsenoside Rd, can be considered as potential Q-markers for American ginseng.ConclusionThe study has demonstrated that the Chinmedomics is an effective, comprehensive and fire-new method for discovering the Q-markers of TCM, and it may be more reasonable choices to establish quality standards of TCM.     

Pharmacogenetics: Implications for drug development,patients and society

Clinical diagnosis and prescribing is a highly sophisticated art, requiring many years of training. Despite this, the response of individual patients to medicines (where efficacy and safety have been proven in large clinical studies) can still be somewhat variable. Knowledge of the likely response of an individual patient to a medicine will enable physicians to select the most effective and well-tolerated treatment for that patient. Pharmacogenetics is the use of genetic science and technology to provide new insights on the likely response to a particular medicine. (This contrasts with the more conventional use of genetics to elicit information about diseases.) Pharmacogenetic medicine response profiles could take the form of either gene-specific profiles, which will determine the gene variants that affect the mode of action and the metabolism of the medicine, or abbreviated single nucleotide polymorphism profiles, which are correlated with medicine-related phenotypes. In general, pharmacogenetic medicine response profiles will be unlikely to provide additional information about the patient's disease or predict any other diseases. The ethical, legal and social issues associated with medicine response profiles are clearly of a quite different magnitude from those associated with the gene-specific tests for disease.     

Methods for the absolute quantification of N-glycan biomarkers

BackgroundMany treatment options especially for cancer show a low efficacy for the majority of patients demanding improved biomarker panels for patient stratification. Changes in glycosylation are a hallmark of many cancers and inflammatory diseases and show great potential as clinical disease markers. The large inter-subject variability in glycosylation due to hereditary and environmental factors can complicate rapid transfer of glycan markers into the clinical practice but also presents an opportunity for personalized medicine.Scope of reviewThis review discusses opportunities of glycan biomarkers in personalized medicine and reviews the methodology for N-glycan analysis with a specific focus on methods for absolute quantification.Major conclusionsThe entry into the clinical practice of glycan markers is delayed in large part due to a lack of adequate methodology for the precise and robust quantification of protein glycosylation. Only absolute glycan quantification can provide a complete picture of the disease related changes and will provide the method robustness required by clinical applications.General significanceGlycan biomarkers have a huge potential as disease markers for personalized medicine. The use of stable isotope labeled glycans as internal standards and heavy-isotope labeling methods will provide the necessary method precision and robustness acceptable for clinical use. This article is part of a Special Issue entitled “Glycans in personalized medicine” Guest Editor: Professor Gordan Lauc.     

Primary Menopausal Insomnia: Definition,Review, and Practical Approach

ObjectiveTo present a case of primary menopausal insomnia with hot flashes to introduce recent changes in technology and nomenclature of sleep medicine and to review presentation, diagnosis, and therapies for menopausal insomnia.MethodsClinical findings and results of sleep evaluation in the menopausal study patient are presented with details about polysomnography performed before and after therapy with pregabalin.ResultsA 56.5-year-old female athlete with severe hot flashes and insomnia of 12 years duration was treated with pregabalin, which ameliorated the hot flashes and sweats and improved sleep quality and architecture. Menopause is associated with hormonal and metabolic changes that disrupt sleep. Disruption of sleep can in turn lead to morbidity and metabolic sequelae. Hormonal treatment, although effective, carries risks unacceptable to many patients and physicians. To date, nonhormonal therapies of symptomatic menopause have not been objectively studied for effects on sleep efficiency and architecture. Primary menopausal insomnia is insomnia associated with menopause and not attributable to secondary causes. Polysomnographically, it seems characterized by a high percentage of slow-wave (N3) sleep, decreased rapid eye movement sleep, cyclic alternating pattern, and arousals.ConclusionsPrimary menopausal insomnia is probably mediated through a mechanism separate from hot flashes, and one can occur without the other. Thermal dysregulation and sleep abnormalities of menopause are probably related to more general changes mediated through loss of estrogenic effects on neuronal modulation of energy metabolism, and more clinical direction is expected as this research field develops. Identification of sleep disorders in menopausal women is important, and polysomnographic evaluation is underused in both clinical and research evaluations of metabolic disturbances. (Endocr Pract. 2011; 17:122-131)     

Moderate ischemic mitral regurgitation (IMR) and metabolic syndrome: where are we now and where are we going?

Background

The metabolic syndrome appears to affect 10% to 25% of adult population worldwide. Several studies have described the association between metabolic syndrome and ischaemic heart disease, however, none linked metabolic syndrome to ischemic mitral regurgitation, a serious clinical problem facing both the cardiologists and cardiac surgeons. Ischemic mitral regurgitation is mitral insufficiency caused by myocardial infarction. The myocardial ischemia can result in altered ventricular geometry, leading to mitral insufficiency. Interestingly metabolic syndrome showed more pronounced alteration of left ventricular geometry and function especially in obese subjects.

Presentation of the hypothesis

We have recently proposed that there is link between metabolic syndrome and ischemic mitral regurgitation and associated complications. Operative strategy for moderate ischaemic mitral regurgitation continues to be debated between revascularisation alone and concomitant valve repair at the time of coronary artery bypass surgery. Each of the above group has published studies, with results supporting each argument.

Testing the hypothesis

Generally speaking the treatments available for metabolic syndrome are based in both life style modification (dietary advice and advice to increase physical activity) and medical treatment to enhance insulin sensitivity. Randomised controlled trials may show whether the current available treatment of metabolic syndrome may have an impact on moderate ischemic mitral regurgitation.

Implications of the hypothesis

Metabolic syndrome was shown to alter left ventricular geometry and therefore it is possible to postulate that the variation in the response of different patients with moderate ischemic mitral regurgitation to current management may be attributed to the absence and presence of metabolic syndrome. Research testing of this hypothesis in the future may reveal whether concomitant treatment of metabolic syndrome will play part in the management of moderate ischemic mitral regurgitation.