Effect of berberine on hyperglycaemia and gut microbiota composition in type 2 diabetic Goto-Kakizaki rats

BACKGROUND A recent investigation showed that the prevalence of type 2 diabetes mellitus(T2DM)is 12.8%among individuals of Han ethnicity.Gut microbiota has been reported to play a central role in T2DM.Goto-Kakizaki(GK)rats show differences in gut microbiota compared to non-diabetic rats.Previous studies have indicated that berberine could be successfully used to manage T2DM.We sought to understand its hypoglycaemic effect and role in the regulation of the gut microbiota.AIM To determine whether berberine can regulate glucose metabolism in GK rats via the gut microbiota.METHODS GK rats were acclimatized for 1 wk.The GK rats were randomly divided into three groups and administered saline(Mo),metformin(Me),or berberine(Be).The observation time was 8 wk,and weight,fasting blood glucose(FBG),insulin,and glucagon-like peptide-1(GLP-1)were measured.Pancreatic tissue was observed for pathological changes.Additionally,we sequenced the 16S rRNA V3-V4 region of the gut microbiota and analysed the structure.RESULTS Compared with the Mo group,the Me and Be groups displayed significant differences in FBG(P<0.01)and GLP-1(P<0.05).A significant decrease in weight and homeostatic model assessment-insulin resistance was noted in the Be group compared with those in the Me group(P<0.01).The pancreatic islets of the Me-and Be-treated rats showed improvement in number,shape,and necrosis compared with those of Mo-treated rats.A total of 580 operational taxonomic units were obtained in the three groups.Compared to the Mo group,the Me and Be groups showed a shift in the structure of the gut microbiota.Correlation analysis indicated that FBG was strongly positively correlated with Clostridia_UCG-014(P<0.01)and negatively correlated with Allobaculum(P<0.01).Body weight showed a positive correlation with Desulfovibrionaceae(P<0.01)and a negative correlation with Akkermansia(P<0.01).Importantly,our results demonstrated that Me and Be could significantly decrease Bacteroidetes(P<0.01)and the Bacteroidetes/Firmicutes ratio(P<0.01).Furthermore,Muribaculaceae(P<0.01;P<0.05)was significantly decreased in the Me and Be groups,and Allobaculum(P<0.01)was significantly increased.CONCLUSION Berberine has a substantial effect in improving metabolic parameters and modulating the gut microbiota composition in T2DM rats.

Association of Hyperhomocysteinaemia with Hyperglycaemia, Dyslipidaemia, Hypertension and Obesity

There is conflicting scientific data about the link between, high homocysteine (Hcy) levels in the general population, and obesity. This is a case-control study aimed to assess the role of hyperhomocysteinemia in obesity and its associated illnesses, including hypertension, dyslipidemia, and hyperglycemia in Gezira state, Sudan. Two hundred and eleven participants were included in the study, 140 were obese (117 females and 23 males) and 71 were normal weight control, the obese median age was 49.49 ± 12.2 years. The control group consisted of 71 individuals with an average age of 45.78 ± 17.67 years. Among those who were already known to be obese, 67 (47.9%) reported having type II diabetes mellitus, 71 (50.7%) reported having hypertension, and 35 (25%) were obese without having either diabetes or hypertension. Three mls of venous blood from each participant were collected in the morning after a 12 h overnight fasting in Lithium heparin containers then the plasma was separated and stored at -80&deg;C for analysis. Serum Hcy and lipid profile were measured using the enzymatic method by Cobas C 411 analyzer. In comparison to obese non-hypertensive, the results showed that obese hypertensive with Hcy levels > 15 mol/L had a considerably increased risk (OR 1.12). When Hcy levels > 15 mol/L were compared to obese diabetics and obese non-diabetics, insignificant difference was shown (P: 0.345). Males had a higher likelihood of having hyperhomocysteinemia than females did (OR 1.2). Homocysteine, cholesterol triglyceride, LDL, and HDL mean values were compared between case and control groups using the independent sample t-test, and the results revealed statistically significant (P: <0.05). Relationships between hyperhomocysteinaemia and cholesterol, triglycerides, LDL, and HDL in the group of obese individuals were not statistically significant (P: 0.574, 0.265, 0.748, and 0.14), respectively. Obesity and Hcyconcentrations were shown to be substantially correlated. However, there was no statistically significant association between baseline plasma Hcy levels and hyperglycemia, hypertension, or dyslipidemia.

Neuroimaging features in a patient with non-ketotic hyperglycaemic seizures: A case report

BACKGROUND Non-ketotic hyperglycaemic(NKH)seizures are a rare neurological complication of diabetes caused by hyperglycaemia in non-ketotic and non-hyperosmotic states.The clinical characteristics of NKH seizures are atypical and lack unified diagnostic criteria,leading to potential misdiagnoses in the early stages of the disease.CASE SUMMARY This report presents a rare case of NKH seizures in a 52-year-old male patient with a history of type 2 diabetes mellitus.We performed comprehensive magnetic resonance imaging(MRI)studies at admission,12 d post-admission,and 20 d post-discharge.The imaging techniques included contrast-enhanced head MRI,T2-weighted imaging(T2WI),fluid-attenuated inversion recovery(FLAIR),diffusion-weighted imaging,susceptibility-weighted imaging,magnetic reso-nance spectroscopy(MRS),and magnetic resonance venography.At the time of admission,T2WI and FLAIR of the cranial MRI showed that the left parieto-occipital cortex had gyrus-like swelling and high signal,and subcortical stripes had low signal.MRS showed a reduced N-acetylaspartate peak and increased creatine and choline peaks in the affected areas.A follow-up MRI 20 d later showed that the swelling and high signal of the left parieto-occipital cortex had disappeared,and the low signal of the subcortex had disappeared.CONCLUSION This case study provides valuable insights into the potential pathogenesis,diagnosis,and treatment of NKH seizures.The comprehensive MRI findings highlight the potential utility of various MRI sequences in diagnosing and characterizing NKH seizures.

基于FAERS数据库的PCSK9抑制剂和他汀类药物的高血糖不良反应分析

目的:基于FDA不良事件报告系统(FDA Adverse Events Reporting System,FAERS),比较PCSK9抑制剂和他汀类药物引起高血糖的风险。方法:利用FAERS数据库,收集2016年至2023年第3季度,首要怀疑药物为阿利西尤单抗、依洛尤单抗、阿托伐他汀、瑞舒伐他汀,不良事件为高血糖的报告,采用报告比值比法(ROR)评价PCSK9抑制剂和他汀类药物导致高血糖的风险大小。结果:根据FAERS数据库,与阿托伐他汀及瑞舒伐他汀相比,阿利西尤单抗发生高血糖的ROR(95%CI)分别为0.628(0.545,0.724)和0.307(0.263,0.357);依洛尤单抗发生高血糖的ROR(95%CI)分别为0.817(0.750,0.889)和0.399(0.361,0.441),均未产生不良反应信号。与其他所有药物相比,阿利西尤单抗和依洛尤单抗发生高血糖的ROR(95%CI)分别为1.488(1.315,1.682)和1.934(1.845,2.027),均产生不良反应信号。结论:基于FAERS数据库,PCSK9抑制剂较他汀类药物引起高血糖的风险低,值得引起临床关注。

Hypothesis that alpha-amylase evokes regulatory mechanisms originating in the pancreas,gut and circulation,which govern glucose/insulin homeostasis

The anti-incretin theory involving the abolishment of diabetes type(DT)II by some of methods used in bariatric surgery,first appeared during the early years of the XXI century and considers the existence of anti-incretin substances.However,to date no exogenous or endogenous anti-incretins have been found.Our concept of the acini-islet-acinar axis assumes that insulin intra-pancreatically stimulates alpha-amylase synthesis(“halo phenomenon”)and in turn,alphaamylase reciprocally inhibits insulin production,thus making alpha-amylase a candidate for being an anti-incretin.Additionally,gut as well as plasma alphaamylase,of pancreatic and other origins,inhibits the appearance of dietary glucose in the blood,lowering the glucose peak after iv or oral glucose loading.This effect of alpha-amylase can be interpreted as an insulin down regulatory mechanism,possibly limiting the depletion of pancreatic beta cells and preventing their failure.Clinical observations agree with the above statements,where patients with high blood alpha-amylase concentrations are seldom obese and seldom develop DT2.Obese-DT2,as well as DT1 patients,usually develop exocrine pancreatic insufficiency(EPI)and vice versa.Ultimately,DT2 patients develop DT1,when the pancreatic beta cells are exhausted and insulin production ceases.Studies on biliopancreatic diversion(BPD)and on BPD with duodenal switch,a type of bariatric surgery,as well as studies on EPI pigs,allow us to observe and investigate the above-mentioned phenomena of intra-pancreatic interactions.

血糖水平对急性冠脉综合征患者近期预后的影响

目的探讨血糖水平对急性冠脉综合征（ACS）近期预后的影响机制及处理。方法对366例急性冠脉综合征患者，根据其清晨血糖水平分为正常、应激性高血糖（SHG）、糖尿病（DM）3个组，再按照血糖水平≤6．1mmol／L、6．2～10．0mmol／L、≥10．0mmol／L分为Q1、Q2、Q33个层。对所有资料进行回顾性分析。结果366例ACS合并SHG者126人，其中发生急性心肌梗死（AMI）48例、左室功能不全（LVF）17例、严重心律失常11例、心原性猝死（CD）1例。ACS伴有DM者88人，发生AMI46例、LVF22例、恶性心律失常16例、CD7例。血糖正常组152人，发生AMI12例、LVF7例，恶性心律失常3例、CD0例。结论无论DM患者还是应激性高血糖患者血糖升高均使ACS近期不良预后发生率增加，临床应加强对ACS患者的血糖控制。

急性心肌梗死伴应激性高血糖患者应用胰岛素的临床观察

目的观察急性心肌梗死(AMI)伴应激性高血糖患者进行胰岛素治疗的临床疗效。方法76例AMI伴应激性高血糖患者随机均分为治疗组和对照组,分别在治疗前和治疗后第7天抽取静脉血,测定空腹血糖、血清肿瘤坏死因子(TNF)-α、核因子(NF)-κB和C-反应蛋白(CRP),并比较两组的临床疗效。结果治疗后,治疗组和对照组的CRP和TNF-α水平均较治疗前显著下降(P值均<0.01)。治疗组的空腹血糖和NF-κB水平较治疗前显著下降(P值均<0.01),而对照组的差异无统计学意义(P值均>0.05)。治疗组总的心脏事件(严重心律失常、心力衰竭、死亡)发生率为7.9%,显著低于对照组的26.3%(P<0.05)。治疗组的住院天数显著短于对照组(P<0.05)。结论胰岛素能抑制AMI合并应激性高血糖患者炎性介质的表达,从而改善其预后。

内质网应激与动脉粥样硬化

在动脉粥样硬化的病理机制的研究中,内质网应激的作用越来越受到关注。本文拟就内质网应激与动脉粥样硬化的关系作一综述。内质网应激通过在炎症反应、脂质代谢异常、细胞凋亡中起的潜在作用,可能参与动脉粥样硬化发生和发展的机理。同时,血浆高半胱氨酸、高血糖等独立危险因子与内质网应激过程相互作用而诱导动脉粥样硬化。

高尿酸血症与其他代谢异常的相关性

目的探讨高尿酸血症与其他代谢异常的相关性,指导临床对高尿酸血症患者的诊治。方法对2008年本院2074名健康体检人群进行横断面调查,描述高尿酸血症和其他代谢异常在健康体检人群的患病率,通过双变量分析和Logistic多元回归分析,探讨高尿酸血症和其他代谢异常的相关性。结果本组人群总高尿酸血症患病率为14.27%,男性为21.36%,女性为11.48%;其他各代谢异常的患病率分别为肥胖12.07%,高血压24.70%,空腹高血糖19.46%,高总胆固醇血症36.38%,高甘油三酯血症28.68%,低高密度脂蛋白-胆固醇血症33.80%,高低密度脂蛋白-胆固醇血症35.25%,高非高密度脂蛋白-胆固醇血症22.59%,脂肪肝40.28%;高尿酸血症组其他代谢异常的患病率均较非高尿酸血症组高,调整年龄、性别后两组比较差异仍有统计学意义;双变量相关分析显示血清尿酸值与年龄、性别、体重指数、收缩压、舒张压、高密度脂蛋白-胆固醇、低密度脂蛋白-胆固醇、总胆固醇、甘油三酯、非高密度脂蛋白-胆固醇、空腹血糖、肌酐、脂肪肝均具有显著相关性。多元Logistic回归分析发现血清尿酸水平与肥胖、高血压、低高密度脂蛋白-胆固醇、高甘油三酯、脂肪肝独立相关。结论高尿酸血症与肥胖、高血压、血脂紊乱、脂肪肝等代谢异常独立相关,其可能增加上述代谢异常的发生风险。

急性心肌梗死后应激性高血糖诊断标准的探讨

目的探讨急性心肌梗死后应激性高血糖的诊断标准。方法对264例急性心肌梗死患者早期空腹血糖及近期预后进行回顾性对比分析。结果非糖尿病组应激性血糖≥6.1mmol/L时心力衰竭及心源性休克的发生率升高(P<0.05),严重心律失常的发生率升高(差异无统计学意义),死亡率亦升高(P<0.05)。糖尿病组应激性血糖≥8.0mmol/L时心力衰竭及心源性休克、严重心律失常的发生率及死亡率均升高(差异无统计学意义)。结论从近期并发症及死亡率表明,非糖尿病患者急性心肌梗死后血糖≥6.1mmol/L,糖尿病患者急性心肌梗死后血糖≥8.0mmol/L可作为急性心肌梗死后应激性高血糖的诊断标准。

2型糖尿病对骨再生与修复的影响

目的探讨2型糖尿病对大鼠胫骨牵引成骨过程中的骨形成的影响。方法雄性糖尿病大鼠和Zucker正常大鼠各10只,检测体重、血糖、尿糖和尿酮,以观察糖尿病变化情况。1周后,所有大鼠接受左胫骨中上段低能横行截骨、安置延长外固定架。第2天起开始每天胫骨延长, 速率为0.2 mm 2次/d. 共14 d。然后,利用放射学和组织学等方法,分别测定胫骨延长间隙中新生骨量,增殖细胞数量,血液生化指标。结果糖尿病大鼠显示肥胖、高血糖、高胰岛素血症(胰岛素不敏感),尿糖阳性等2型糖尿病特征。糖尿病大鼠亦显示胫骨延长间隙中新生骨量显著降低,并伴有增殖细胞数量降低及血清骨钙素下降。结论2型糖尿病可引起骨再生与修复障碍,这可能与长期慢性高血糖所致代谢紊乱,导致成骨细胞的增殖分化障碍有关。

WJD 5^(th) Anniversary Special Issues(2): Type 2 diabetes Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?

Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality,and are disproportionately affected by cardiovascular disease.Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension,dyslipidaemia and obesity in these patients.However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors.Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus.Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events.Many of these risk factors could be common history for both di-abetes mellitus and cardiovascular disease,reinforcing the postulate that both disorders come independently from"common soil".The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.

非酮症糖尿病癫痫临床分析

目的：探讨非酮症糖尿病性癫痫的临床规律，提高早期诊断率。方法：对20例非酮症糖尿病性癫痫的临床资料进行回顾性分析。结果：12例糖尿病性患者在血糖控制不理想状态下发生癫痫，8例患者以癫痫作为糖尿病的首发症状。15例表现为部分运动性发作，占75%。应用胰岛素积极控制血糖是主要治疗措施，避免应用苯妥英钠。结论：提高对本病的认识，早期诊断，降低血糖是控制癫痫发作的关键。

肠内营养与肠外营养对老年患者术后应激性高血糖影响的对比研究

目的研究老年患者术后采用肠内营养(EN)和肠外营养(PN)对应激性高血糖的不同影响,为老年患者术后应激性高血糖的防治提供可靠依据。方法选择60岁以上行胆囊切除、胆管取石的老年患者60例,术后随机分为EN组及PN组,每组30例,比较术后血糖及胰岛素变化情况及术后并发症以及伤口愈合情况。结果EN组应激性高血糖发病率明显低于PN组(P<0.01),术后并发症以及伤口愈合情况均优于PN组(P<0.01)。结论术后肠内营养对预防老年患者术后应激性高血糖的发生有良好作用。

代谢综合征及其组分聚集对肺功能的影响

目的:探讨代谢综合征(metabolic syndrome,MS)患者肺功能的变化以及代谢综合征组分的聚集对肺功能的影响。方法:检测并比较43例代谢综合征(MS)患者和61例非代谢综合征(non-metabolic syndrome,non-MS)患者的肺功能,进一步根据MS定义中代谢异常组分的累加评分(0～4分)分为5组,比较各组间肺功能变化。结果:MS组肺活量(FVC)、1秒钟用力呼气容积(FEV1)、最大通气量(MVV)、肺一氧化碳弥散量(DLco)均明显低于non-MS组(P<0.01)。随着代谢综合征组分的增加,FVC、FEV1、MVV、DLco均有下降。结论:MS患者较non-MS患者有明显的肺功能减退,且随着代谢异常的累积,肺功能的损害也有所增加。

绝经激素治疗与代谢综合征风险研究进展

代谢综合征(包括腹型肥胖、糖代谢异常、脂代谢紊乱、高血压等)因与心血管病风险因素密切相关,已成为全球公共健康的一个主要挑战。绝经后激素治疗的应用已有半个多世纪,但绝经后激素治疗(menopause hormone therapy,MHT)的适应证及理想候选适应证仍然不清楚。绝经妇女心血管病风险的增高是这组人群死亡的主要原因。雌激素的降低与许多围绝经与绝经后妇女总胆固醇、三酰甘油、低密度脂蛋白胆固醇的增加,胰岛素抵抗的增加及血压的升高相关。这些变化的参数是代谢综合征的主要组分。目前推荐MHT作为血管舒缩症状的金标准治疗,其对代谢综合征组分及心血管病风险的益处仍不清楚,本文将对MHT与代谢综合征组分的风险及益处进行综述。

30例重型颅脑损伤患者保守治疗的临床分析

目的分析30例重型颅脑损伤患者保守治疗过程,探讨救治方法。方法回顾2003-2007年重型颅脑损伤患者保守治疗病例30例,分析治疗方案和结果。结果30例患者通过治疗,28例恢复良好并正常出院(伴不同程度记忆力减退和头痛),2例死亡。结论患者在治疗中会出现高血糖、电解质紊乱、烦躁、消化道出血等并发症,医师要综合考虑问题,积极处理,才能得到良好疗效。

心血管疾病与糖代谢异常

近年来，我国心血管疾病与糖尿病的发生率均呈上升趋势，两者之间的关系愈来愈受到人们的关注。欧洲心脏调查和中国心脏调查均证实，冠心病与糖尿病及高血糖状态关系密切。有报道，冠心病、高血压住院患者糖代谢异常率高达60．6％。根据大量的循证医学研究，EASD和ESC联合发布了《糖代谢异常和心血管疾病诊治的欧洲指南》。因此，心血管科医师应当高度关注心血管疾病患者糖代谢异常的病态。

Rho激酶抑制剂对高血糖合并高血脂大鼠内皮功能的影响

目的高血糖合并高血脂在临床心血管疾病中非常普遍,文中通过观察高血糖高血脂大鼠主动脉内皮功能和Rho激酶的表达,研究Rho激酶与内皮功能的关系及Rho激酶抑制剂对其的影响。方法健康雄性Wistar大鼠随机数字表法分成空白对照组(5只)、模型组(10只)、药物组(10只)。模型组和药物组先采用经尾静脉注射链脲佐菌素加高脂饮食制备高血糖高血脂的模型,再分别给予等渗盐水、Rho激酶抑制剂法舒地尔腹腔注射治疗4周。实验结束后测定3组大鼠血糖(VBG)、三酰甘油(TG)、血清总胆固醇(TC)、血清低密度脂蛋白胆固醇(LDL)、血清高密度脂蛋白胆固醇(HDL)、一氧化氮合酶(e NOS)、内皮素(ET-1)表达水平以及肌球蛋白磷酸酶结合亚基1(MYPT-1)和Rho激酶的mRNA表达。HE染色观察内皮形态学变化。结果与空白对照组比较,模型组VBG、ET-1、MYPT-1、ROCK和Rho A mRNA水平明显升高[(6.18±1.14)mmol/L vs(26.36±3.25)mmol/L,(72.13±6.13)pg/m L vs(88.22±4.61)pg/m L,(0.54±0.08)vs(1.28±0.17),(0.16±0.20)vs(0.83±0.12),(0.40±0.18)vs(0.78±0.13),P<0.05],TG、TC、LDL亦升高(P<0.05),e NOS水平降低[(24.42±2.13)U/L vs(17.36±1.58)U/L,P<0.05]。与模型组比较,药物组VBG[(17.70±2.69)mmol/L]、ET-1[(75.03±2.50)pg/m L]、MYPT-1(0.74±0.11)、ROCK mRNA水平(0.40±0.08)和Rho AmRNA(0.25±0.07)水平减低(P<0.05),TG[(1.56±0.14)mmol/L]、TC[(6.26±0.43)mmol/L]、LDL[(4.76±0.57)mmol/L]亦降低(P<0.05),e NOS水平[(22.83±1.60)U/L]明显升高(P<0.05)。内皮形态学变化:空白对照组大鼠主动脉内皮形态正常,模型组主动脉内皮病理损伤较重,药物组主动脉内皮损伤明显改善。结论高血糖高血脂大鼠存在内皮功能障碍和Rho激酶高表达,Rho激酶抑制剂可改善其内皮功能。

Treatment approach to type 2 diabetes:Past,present and future

Type 2 diabetes mellitus(DM) is a lifelong metabolic disease, characterized by hyperglycaemia which gradually leads to the development and progression of vascular complications. It is recognized as a global burden disease, with substantial consequences on human health(fatality) as well as on health-care system costs. This review focuses on the topic of historical discovery and understanding the complexity of the disease in the field of pathophysiology, as well as development of the pharmacotherapy beyond insulin. The complex interplay of insulin secretion and insulin resistance developed from previously known "ominous triumvirate" to "ominous octet" indicate the implication of multiple organs in glucose metabolism. The pharmacological approach has progressed from biguanides to a wide spectrum of medications that seem to provide a beneficial effect on the cardiovascular system. Despite this, we are still not achieving the target treatment goals. Thus, the future should bring novel antidiabetic drug classes capable of acting on several levels simultaneously. In conclusion, given the raising burden of type 2 DM, the best present strategy that could contribute the most to the reduction of morbidity and mortality should be focused on primary prevention.