Metabolic disturbances associated with antipsychotic drug treatment in patients with schizophrenia:State-of-the-art and future perspectives

Metabolic disturbances and obesity are major cardiovascular risk factors in patients with schizophrenia,resulting in a higher mortality rate and shorter life expectancy compared with those in the general population.Although schizophrenia and metabolic disturbances may share certain genetic or pathobiological risks,antipsychotics,particularly those of second generation,may further increase the risk of weight gain and metabolic disturbances in patients with schizophrenia.This review included articles on weight gain and metabolic disturbances related to antipsychotics and their mechanisms,monitoring guidelines,and interventions.Nearly all antipsychotics are associated with weight gain,but the degree of the weight gain varies considerably.Although certain neurotransmitter receptorbinding affinities and hormones are correlated with weight gain and specific metabolic abnormalities,the precise mechanisms underlying antipsychoticinduced weight gain and metabolic disturbances remain unclear.Emerging evidence indicates the role of genetic polymorphisms associated with antipsychotic-induced weight gain and antipsychotic-induced metabolic disturbances.Although many guidelines for screening and monitoring antipsychotic-induced metabolic disturbances have been developed,they are not routinely implemented in clinical care.Numerous studies have also investigated strategies for managing antipsychotic-induced metabolic disturbances.Thus,patients and their caregivers must be educated and motivated to pursue a healthier life through smoking cessation and dietary and physical activity programs.If lifestyle intervention fails,switching to another antipsychotic drug with a lower metabolic risk or adding adjunctive medication to mitigate weight gain should be considered.Antipsychotic medications are essential for schizophrenia treatment,hence clinicians should monitor and manage the resulting weight gain and metabolic disturbances.

Cluster analysis reveals a homogeneous subgroup of PCOS women with metabolic disturbance associated with adverse reproductive outcomes

Background:Polycystic ovarian syndrome(PCOS)is a heterogeneous and complex reproductive endocrinological disease that could lead to infertility.There were many attempts to classify PCOS but it remains unclear whether there is a specific subgroup of PCOS that is associated with the best or worst reproductive outcomes of assisted reproductive techniques(ART).Methods:Infertile PCOS patients who underwent their first cycle of in vitro fertilization(IVF)in West China Second University Hospital,Sichuan University from January 2019 to December 2021 were included.Basic clinical and laboratory information of each individual were extracted.Unsupervised cluster analysis was performed.Controlled ovarian stimulation parameters and reproductive outcomes were collected and compared between the different clusters of PCOS.Results:Our analysis clustered women with PCOS into"reproductive","metabolic",and"balanced"clusters based on nine traits.Reproductive group was characterized by high levels of testosterone(T),sex hormone-binding globulin(SHBG),follicular stimulation hormone(FSH),luteinizing hormone(LH),and anti-Müllerian hormone(AMH).Metabolic group was characterized by high levels of body mass index(BMI),fasting insulin,and fasting glucose.Balanced group was characterized by low levels of the aforementioned reproductive and metabolic parameters,except for SHBG.Compared with PCOS patients in reproductive and balanced clusters,those in metabolic cluster had lower rates of good quality day 3 embryo and blastocyst formation.Moreover,PCOS patients in the reproductive cluster had greater fresh embryo transfer(ET)cancelation rate and clinical pregnancy rate after fresh ET than metabolic cluster(odds ratio[OR]=3.37,95%confidence interval[CI]:1.77-6.44,and OR=6.19,95%CI:1.58-24.24,respectively).And compared with PCOS of metabolic cluster,PCOS of balanced cluster also had higher chance for fresh ET cancelation(OR=2.83,95%CI:1.26-6.35).Conclusion:Our study suggested that PCOS patients in metabolic cluster may be associated with adverse reproductive outcomes and might need individualized treatment and careful monitoring before and during ART.

Healing time, calcium and phosphorus contents as well as bone metabolism evaluation after Xianling Gubao-assisted surgical treatment of Colles fracture in elderly women

Objective:To study the effect of Xianling Gubao-assisted surgical treatment on postoperative healing, calcium and phosphorus contents as well as bone metabolism in elderly women with Colles fracture.Methods:A total of 96 elderly female patients with Colles fracture treated in our hospital between June 2013 and December 2015 were selected and randomly divided into two groups, the observation group of patients received Xianling Gubao capsule combined with manual reduction and plaster external fixation therapy, and control group of patients only received reduction and external fixation therapy. The fracture healing time was followed up after treatment, and 3 months after treatment, serum was collected to determine the content of calcium-phosphorus metabolism indexes and bone metabolism indexes.Results:The fracture healing time of observation group was significantly shorter than that of control group;1 month and 3 months after treatment, serum Ca, P, ALP, IGF-1, PDGF, BGP and PICP levels of both groups were significantly higher than those before treatment while CTX-1, tPINP and TRACP-5b levels were significantly lower than those before treatment;serum Ca, P, ALP, IGF-1, PDGF, BGP and PICP levels of observation group after treatment were significantly higher than those of control group while CTX-1, tPINP and TRACP-5b levels were significantly lower than those of control group.Conclusion:Adjuvant Xianling Gubao capsule therapy can promote the Colles fracture healing in elderly women, also improve calcium-phosphorus metabolism, promote bone formation and inhibit bone resorption.

Alterations in gut microbiota are related to metabolite profiles in spinal cord injury

Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8–T10 traumatic spinal cord injury. We used 16 S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids(L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.

2型糖尿病合并多代谢紊乱态靶综合治验1例——仝小林院士教学查房实录

以广安门医院内分泌科中2型糖尿病合并多代谢紊乱案患者为例,邀请仝小林院士进行教学查房,对早中期2型糖尿病合并多代谢紊乱的中医认识、疾病发展与转归、诊疗要点进行阐述。仝小林院士强调肥胖是脾瘅的基石、分类-分期-分证辨治糖尿病、糖肝共治2型糖尿病合并代谢相关脂肪性肝病;治疗上注重运用靶方靶药,关注有效剂量,预防果态,防治脉损,态靶辨治,提高临床疗效。

心房颤动发病机制的相关研究进展

心房颤动(atrial fibrillation,AF)是老年人群中最为常见的心律失常,研究表明其发病机制与衰老、遗传突变、炎症反应、氧化应激、钙稳态异常、代谢异常等有关,越来越多的证据表明上述机制在心房电重构和结构重塑的演变中起着重要作用。在这篇综述中,我们讨论了房颤发生发展可能的分子机制,其中涉及多个典型的炎症途径,以及抗炎治疗、纠正代谢异常等方法对房颤的防治潜力。

BTG2在高脂饮食诱导的非酒精性脂肪肝中的表达及意义

目的探讨BTG2在高脂饮食诱导的非酒精性脂肪肝中的表达及意义。方法将45只SPF级雄性C57BL/6小鼠随机分成为正常对照组(n=10)和模型组(n=35)。在模型组(n=35)连续高脂饮食16周,建立小鼠非酒精性脂肪肝模型。通过实时荧光定量PCR法、免疫组织化学法检测BTG2的表达量和蛋白表达水平,采用苏木精-伊红(HE)染色观察肝组织病理学改变。结果实时荧光定量PCR法检测BTG2在肝脏组织中的表达水平,与对照组相比BTG2的表达量和蛋白表达水平在模型组中显著提高。免疫组织化学法检测结果显示:与对照组相比,模型组中的BTG2蛋白质表达水平显著上调(P<0.01)。结论通过实时荧光定量PCR法、免疫组织化学法检测发现在高脂饮食诱导小鼠肝纤维化模型中的BTG2表达量均显著升高。

慢性肾衰竭患者钙磷代谢紊乱的中西医治疗研究进展

慢性肾衰竭(CRF)患者最常见的一种并发症为钙磷代谢紊乱,其发病率高,易引起心血管事件,导致患者死亡。目前主要通过药物纠正钙磷代谢紊乱,活性维生素D为一线用药,但过度使用会导致高钙血症和高磷血症。磷酸盐结合剂在临床上应用较广泛,疗效佳,但大部分的磷酸盐结合剂都伴随着胃肠道反应。而最新研究的抑制剂EOS789降磷效果显著,且胃肠道反应较少,应用前景广阔。除此之外,联合中医的辨证施治,能有效改善患者药物不良反应,增加患者依从性。透析治疗也尤为重要,且腹膜透析较血液透析效果更好,但最佳纠正钙磷代谢紊乱的透析液钙浓度尚未明确。

Obesity, the Obesity Epidemic, and Metabolic Dysfunction: The Conundrum Presented by the Disconnect between Evolution and Modern Societies

Currently, there is an obesity epidemic in the developed world, with both adults and children being affected. The consequences of this epidemic on health and health outcomes have impact at multiple levels, and it is increasing. The basis for this epidemic, which appears to have emerged with significance ~40 - 50 years ago, is unknown but is believed by many to have much of its basis in poor diets and inactivity/sedentary behaviour. Analysis of the human genome has revealed >100 loci which exhibit risk for development of obesity. Why there are so many loci, and how they benefited humans evolutionarily are unknown. In spite of these limitations, there are urgent needs for effective short-term interventions to assist those with obesity, as well as longer-term needs to effectively prevent development of obesity. For the former, personalized exercise programs, use of prebiotics, optimal nutrition and surgical interventions can be effective for some individuals but more interventions that address cause are also needed. For longer term solutions more detailed genetic and epigenetic understanding of risk will be required. An attractive speculation is that the genomic risk factors for obesity (>100 identified) have been retained evolutionarily to address acute metabolic needs and current conditions have converted such risks to a chronic state, making reversal more difficult and with more consequences, including possible epigenetic modifications of risk genes. Other contributing factors to chronic obesity could also relate to chemical disruptors in the environment over the past 50+ years which may impact metabolic regulation via the established risk genomic risk factors or new variants. Therefore, to effectively control this high impact epidemic of obesity likely requires a more detailed genetic and epigenetic analysis of families with obesity and analysis of isolated populations, as well as a more thorough investigation of chemicals capable of being metabolic disruptors in this regard. Thus, the long-term solution(s) to the obesity epidemic will require a concerted multidisciplinary approach that may be more complex than just becoming more active and avoiding sedentary behavior.

抑郁症患者血清细胞因子水平与症状和代谢指标的相关性

目的探索抑郁症患者血清中细胞因子水平及其与症状和代谢指标的相关性。方法收集首发或急性复发抑郁症患者108例作为病例组,同时招募健康对照47例作为对照组,测定两组血清中细胞因子IL-4、IL-6、IL-10、IFN-γ及TNF-α水平;使用相关性分析的方法分析抑郁症患者血清中细胞因子水平与抑郁症状和焦虑症状及代谢相关指标的关系,抑郁症状使用HAMD评估,焦虑症状使用HAMA评估,代谢指标包括BMI、TBC、CRE、BUN、UA、TG、CHOL、LDL、HDL、GLU及HbA1c。结果病例组血清中IL-4、IFN-γ及TNF-α浓度显著低于对照组(P<0.05),IL-6和IL-10浓度显著高于对照组(P<0.05)。相关性分析表明,IFN-γ(r=0.20,P<0.05)和TNF-α(r=0.20,P<0.05)浓度与HAMA总分呈正相关;病例组IL-6浓度与TG(r=0.19,P<0.05)、CHOL(r=0.26,P<0.01)及LDL(r=0.22,P<0.05)呈正相关,IL-10浓度与CHOL呈正相关(r=0.21,P<0.05),TNF-α水平与CRE呈负相关(r=-0.22,P<0.05)。结论抑郁症患者细胞因子水平存在异常,并且与代谢指标存在一定关联。

抗生素致急性肾损伤代谢组学的研究进展

药物相关肾毒性是住院患者发生急性肾损伤(acute kidney injury,AKI)的一个重要原因,其中抗生素可造成结构性和功能性肾损伤。目前抗生素相关的AKI仍是临床应用中未解决的难题。代谢组学作为近年来发展迅速的技术,最接近人体表型的层面,通过检测机体内代谢物的变化,可直观反映人体的部分生理病理变化。本文综述了近年来抗生素药物相关AKI的代谢组学研究,重点阐述紊乱代谢通路以及潜在生物标志物,并对未来进一步的研究进行展望。

肠道菌群与男性不育症的相关性

肠道菌群数量庞大,门类繁多,在人体免疫、代谢及神经调节等方面发挥着不可替代的作用。研究表明肠道菌群与男性不育之间有着密不可分的联系。男性不育症患者肠道菌群与其炎症反应、代谢调节、神经调节和勃起功能障碍发生发展相关,并可能通过内毒素血症、能量代谢、短链脂肪酸、胰岛素抵抗等影响男性生育能力。此外,现已有少量研究应用饮食调节、补充益生菌调控肠道菌群的方法治疗某些疾病,如口服益生菌联合左卡尼汀可降低肥胖男性的精子DNA碎片率等,这为治疗男性不育症提供了新的思路。对肠道菌群与男性不育症相关性进行综述,探讨肠道菌群在男性不育症中的作用,以期为改进临床治疗方案提供借鉴。

Testing the role of genetic variation of the MC4R gene in Chinese population in antipsychotic-induced metabolic disturbance

Antipsychotic-induced metabolic disturbance(AIMD) is a common adverse effect of antipsychotics with genetics partly underpinning variation in susceptibility among schizophrenia patients. Melanocortin4 receptor(MC4 R) gene, one of the candidate genes for AIMD, has been under-studied in the Chinese patients. We conducted a pharmacogenetic study in a large cohort of Chinese patients with schizophrenia. In this study, we investigated the genetic variation of MC4 R in Chinese population by genotyping two SNPs(rs489693 and rs17782313) in 1,991 Chinese patients and examined association of these variants with the metabolic effects that were often observed to be related to AIMD. Metabolic measures, including body mass index(BMI), waist circumference(WC), glucose, triglyceride, high-density lipoprotein(HDL), and low-density lipoprotein(LDL) levels were assessed at baseline and after 6-week antipsychotic treatment. We found that interaction of SNP×medication status(drug-na?ve/medicated) was significantly associated with BMI, WC, and HDL change %, respectively. Both SNPs were significantly associated with baseline BMI and WC in the medicated group. Moderate association of rs489693 with WC, Triglyceride, and HDL change % were observed in the whole sample. In the drug-na?ve group, we found recessive effects of rs489693 on BMI gain more than 7%, WC and Triglyceride change %, with AA incurring more metabolic adverse effects. In conclusion, the association between rs489693 and the metabolic measures is ubiquitous but moderate. Rs17782313 is less involved in AIMD. Two SNPs confer risk of AIMD to patients treated with different antipsychotics in a similar way.

青年职业女性无症状高尿酸血症伴代谢失调的现况分析

目的分析青年职业女性无症状高尿酸血症与糖类、脂类、肾功能等代谢失调之间的关系,探讨及早控制青年职业女性血尿酸(SUA)水平的重要性。方法选取2020年5月至2021年4月在江苏省人民医院参加体检的20~45岁青年职业女性共29987人,按研究对象年龄段分五组,比较不同年龄段青年职业女性的无症状高尿酸血症患病率;根据血尿酸水平分三组,比较不同等级尿酸水平者空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG),高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血肌酐、血尿素异常率。结果无症状高尿酸血症总体患病率为7.69%,5个年龄段(>20~25岁、>25~30岁、>30~35岁、>35~40岁、>40~45岁)无症状高尿酸血症患病率分别为9.35%、9.03%、7.93%、7.40%、5.78%;3个SUA组(≤275μmol/L、>275~360μmol/L、>360μmol/L)FBG受损率分别为0.68%、1.49%、3.25%;高TC率分别为5.54%、7.39%和11.37%;高TG率分别为1.43%、3.61%和10.67%;低HDL-C率分别为1.97%、3.74%、7.20%;高LDL-C率分别为2.39%、3.79%、6.20%;高血肌酐率分别为1.86%、4.52%和7.94%;高血尿素率分别为0.68%、0.86%和1.52%。结论青年职业女性中>20~25岁年龄段无症状高尿酸血症患病率最高,SUA水平较高者更倾向于合并代谢异常。血尿酸水平中等程度升高者代谢失调与低血尿酸水平人群有明显差异,也应引起足够重视。

Study on Prevention and Treatment of Diabetes in Middle and Aged Women with Kidney Deficiency and Bone Metabolic Disturbance

Objective: To study the therapeutic effect of Chinese herbal medicine (CHM) for supplementing Qi, activating blood circulation and tonifying Kidney on prevention and treatment of diabetes in middle and aged women with Kidney Deficiency and bone metabolic disturbance. Methods: Clinical observation was taken in 52 patients, who were divided into two groups, the control group (treated with hypoglycemic agent alone) and the treated group (treated with hypoglycemic agent and CHM). Results: Before treatment, patients in both groups showed obviously higher blood alkaline phosphatase, β2-microglobulin (β2-MG) level, urinary β2-MG, calcium and phosphorus level, but lower serum estradiol level than those in normal subjects. After 3 months' treatment, no apparent change in serum estradiol level was observed, but other parameters were all lowered obviously in the two groups, with the changes revealed more obviously in the treated group. The symptoms of Kidney Deficiency, such as lumbodorsal pain, fatigue, palpitation and vertigo, were improved after treatment, which was also more obviously in the treated group. Conclusion: CHM for supplementing Qi, activating blood circulation and tonifying Kidney was effective in improving Kidney Deficiency and mineral substance loss in bones in middle and aged diabetic women patients. The CHM and western drugs acted synergistically.

The association of olanzapine-induced metabolic disturbance related measures with TCF7L2 gene expression

Objective To investigate the relationship between olanzapine induced metabolic disturbance related measures and TCF7L2 gene expression.Methods Thirty adult C57BL/61 mice,in accordance with the random number table,were divided into 3 groups that were

体检人群代谢综合征与血清胱抑素C水平的相关性

目的:探讨体检人群代谢综合征(metabolic syndrome,Met S)与血清胱抑素C(cystatin C,Cys-C)水平的相关性。方法:以中南大学湘雅三医院健康管理中心6 783例体检人群为研究对象进行横断面研究。将人群分为3组,其中Met S组1 578例,代谢异常(metabolic disturbance,Met D)组3 617例,健康对照(healthy control,HC)组1 588名。收集一般资料、进行体格检查及生化指标检测。比较各组间一般临床资料的特点;采用多因素logistic回归分析Cys-C对Met S的影响,协方差分析代谢异常组分数与Cys-C水平的关系。结果:与HC组比较,Met S组和Met D组Cys-C水平明显增高;且Met S组明显高于Met D组(P<0.05)。校正年龄、性别、血压、吸烟、饮酒、绝经状态、腰围、体质量指数、血糖、血脂、估算肾小球滤过率、血尿酸、尿微量白蛋白、超敏C反应蛋白、同型半胱氨酸因素后,Cys-C高水平是Met S的独立危险因素(OR=1.951,95%CI 1.265~3.009,P<0.05)。随着Cys-C水平四分位数增高,其患Met S的优势比增加(P<0.05)。随着代谢异常组分数增加,血清Cys-C水平显著增高(P<0.01)。结论:体检人群中Cys-C与Met S有明显相关性,且Cys-C水平可能与Met S代谢异常的严重性有关。

肥胖症肠道菌群与炎症的研究进展

人体肠道内存在着多种多样的菌群,研究表明这些肠道菌群在肥胖发生过程中非常重要。肠道菌群调节宿主的能量吸收及营养代谢,肠道无菌小鼠在喂养高脂饮食时,体重增加不如正常小鼠明显,说明肠道菌群增加了宿主从肠道吸收的热量。肠道菌群改变产生过量的脂多糖(LPS),LPS入血引发炎症反应,促进高脂饮食导致的肥胖及代谢综合征。肠道菌群通过降低肠黏膜的Fiaf表达,增加脂肪在内脏的沉积。不同免疫状态对肠道菌群也有影响。肠道菌群成为肥胖发生的环境因素,与宿主、饮食等相互作用,调节着宿主的能量代谢。使用一些抗生素或益生菌可以改变肠道菌群,改善代谢综合征,这为治疗肥胖提供了可能的方向。

糖脂宁胶囊对2型糖尿病合并高脂血症大鼠糖、脂代谢的影响

目的:观察糖脂宁胶囊对2型糖尿病合并高脂血症大鼠血糖、血脂及胰岛素抵抗的影响。方法:采用高脂饮食和链脲佐菌素(streptozotic,STZ)制造2型糖尿病合并高脂血症大鼠模型,观察糖脂宁胶囊对大鼠血糖、血脂4项、血清胰岛素含量、胰岛素敏感指数的影响及大鼠肝脏、胰腺的病理损害。结果:糖脂宁胶囊可降低实验大鼠的血糖水平,显著降低实验大鼠血清甘油三酯、胆固醇、低密度脂蛋白水平,升高高密度脂蛋白水平,同时改善模型大鼠胰腺、肝脏的病理损害,明显增加胰岛素敏感性。结论:糖脂宁胶囊有糖脂双调的作用,并能显著增加胰岛素的敏感性。

原发性醛固酮增多症患者糖代谢紊乱的患病情况

目的评价原发性醛固酮增多症(下称原醛症)患者糖代谢紊乱的患病情况。方法检测115例原醛症患者的血压、血尿醛固酮、血尿电解质、血浆肾素活性基础及激发值,并行OGTT。结果(1)原醛症患者中糖代谢紊乱患病率为47.0%,其中糖耐量减低者29.6%,糖尿病者17.4%。(2)根据OG-TT结果分为伴有糖代谢紊乱组(组1)及不伴有糖代谢紊乱组(组2)。两组进行比较,组1年龄大于组2,OGTT各点血糖均以组1为高,组1餐后60、120及180min血胰岛素较组2为高,两组空腹及餐后30min血胰岛素比较差异无统计学意义,两组ISI、HOMA-IR、AUCG及AUCI比较差异有统计学意义。(3)组1血醛固酮高于组2,血钾低于组2;两组尿醛固酮、血浆肾素活性基础值及激发值、尿钾、收缩压及舒张压比较,差异均无统计学意义。结论原醛症患者糖代谢紊乱的患病率升高,一经确诊,即应积极治疗。