Peroxisome proliferator-activated receptor-gamma Pro12Ala polymorphism, Helicobacter pylori infection and non-cardia gastric carcinoma in Chinese

BACKGROUND: Peroxisome proliferator-activated receptor gamma inhibits the growth and induces apoptosis of gastric cancer cells. A common polymorphism at codon 12 of this gene (Pro12Ala) has been shown to confer protection against diabetes and colorectal cancer. AIM: To study the association between peroxisome proliferator-activated receptor gamma gene polymorphism, Helicobacter pylori infection and gastric cancer in Chinese. METHODS: One hundred and four consecutive patients with non-cardia gastric adenocarcinoma and 104 matched controls were examined. Peroxisome proliferator-activated receptor gamma Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequency of peroxisome proliferator-activated receptor gamma G (Ala12) allele was significantly higher among cancer patients (19.2%) than in control (8.7%; OR 2.5, 95% CI 1.1-5.8). While H. pylori infection was more prevalent in gastric cancer patients (OR 3.0; 95% CI 1.6-5.7), the combination of peroxisome proliferator-activated receptor gamma G allele and H. pylori infection further increased the risk of gastric cancer (OR 12.8, 95% CI 3.2-50.5). The presence of the Ala12 did not increase the risk of gastric cancer in H. pylori-negative subjects. CONCLUSION: Our study suggests the potential association between peroxisome proliferator-activated receptor gamma polymorphism and H. pylori infection in the development of non-cardia gastric cancer.     

宁夏回汉族 KCNQ1基因多态性与2型糖尿病的相关性研究

目的：探讨 KCNQ1基因 rs231362位点的多态性对宁夏地区回汉民族2型糖尿病易感性的影响。方法采用 PCR －RFLP 技术对宁夏地区回族、汉族的 KCNQ1基因 rs231362多态性基因型及等位基因频率在正常糖耐量人群和2型糖尿病人群中的分布进行分析。结果（1）两个民族中,KCNQ1基因 rs231362多态性在同民族2型糖尿病组和正常糖耐量组的分布差异无统计学意义;（2）KCNQ1基因 T 等位基因的分布频率在两个民族大致相同,回族 T 等位基因频率为0．05,低于本组汉族人群;（3）两个民族正常糖耐量人中,CC 组与 TC ＋TT 组各指标相比差异无统计学意义（P ＞0．05）,而在糖尿病组,回族与汉族 T 等位基因携带者（CT ＋TT）腰围水平 BMI 和腰臀比显著高于 CC 组（P ＜0．05）,而低密度脂蛋白水平低于 CC 组（P ＜0．05）。结论KCNQ1基因变异与宁夏地区两个民族2型糖尿病不相关。KCNQ1基因 rs231362多态性 CT ＋TT 基因型可能与回汉族2型糖尿病的腹型肥胖有关,且携带 T 等位基因者可能对回族2型糖尿病患者的血脂具有调节作用。     

新疆布尔津县哈萨克族糖尿病和高血压流行病学调查研究

目的：调查新疆布尔津县哈萨克族2型糖尿病（T2DM）和高血压（HP）的患病率,为T2DM和HP的预防提供依据。方法：采用随机抽样的调查方法对新疆布尔津县1766例哈萨克族居TT2DM和HP的患病情况进行分析。结果：1766例中T2DM检出率为1．81％,糖耐量异常（IGT）检出率为1．42％,空腹血糖受损（IFG）检出率为0．91％;三组的年龄、收缩压（SBP）、舒张压（DBP）、体重指数（BMI）、腰围,身高比值（WHtR）、总胆固醇（TC）、胰岛素抵抗指数（HOMA—IR）均高于正常糖耐量组（NGT）,差异均有显著性。HP检出率为38．05％,高血压人群的年龄、BMI、WHtR、空腹血糖、TC、TG、HDL、LDL、HOMA—IR均高于血压正常人群,差异有显著性。结论：应对当地居民加强健康教育,提倡合理的饮食结构,控制血糖和血压。关注身体健康。     

Genetic effects,gene-lifestyle interactions,and type 2 diabetes

Type 2 diabetes has become a major public health challenge worldwide. It is now widely accepted that genetic components affect the development of type 2 diabetes, in concert with environmental factors such as lifestyle and diet. Traditional linkage mapping, positional cloning, and candidate gene-based association studies have identified a few genetic variants in genes such as TCF7L2, PPARG, and KCNJ11 that are reproducibly related to the risk of type 2 diabetes. To date, about ten genome-wide association (GWA) studies have been published. These studies discovered new susceptibility genes for type 2 diabetes and provide novel insight into the diabetes etiology. In addition, data especially from lifestyle intervention trials display promising evidence that the genetic variants may interact with changes of dietary habit and physical activity in predisposing to type 2 diabetes. The gene-lifestyle interactions merit extensive exploration in large, prospective studies. The findings from these areas will substantially improve the prediction and prevention of type 2 diabetes.     

脂联素45 T/G基因多态性对利拉鲁肽治疗2型糖尿病患者的临床疗效

目的:研究脂联素45(APM1-45)T/G基因遗传变异对利拉鲁肽治疗2型糖尿病(T2DM)患者的临床疗效以及对T2DM易感性的影响。方法:选取2017年7月至2019年11月期间海口市第三人民医院收治的T2DM患者共95例作为研究对象,均给予利拉鲁肽进行为期14周的治疗,记录不同基因型患者治疗前后的血糖水平、BMI指数和mRNA相对表达等指标变化,统计不良反应的发生情况。结果:APM1-45(rs2241766)位点在研究人群中的基因分布频率为:TT型46例(48.42%),TG型43例(45.26%),GG型6例(6.32%),三种基因型分布频率符合哈迪温伯格平衡(P=0.328)。治疗后,各组患者的餐后2小时血糖(2h PG)、糖化血红蛋白(HbA1c)、空腹血糖(FPG)和BMI相关指标相比治疗前均下降明显,且存在统计学差异(P<0.05);TT基因型患者的各项指标与TG/GG基因型患者相比,下降更多,但二者相比不存在统计学差异(P>0.05)。mRNA相对表达方面,相对于TG/GG基因型患者,TT基因型患者的mRNA的相对表达明显偏低,二者差异具有统计学意义(P<0.05)。患者整体不良反应发生情况较少,各组之间无统计学差异。结论:对2型糖尿病患者,利拉鲁肽进行治疗具有明显效果,在显著降低血糖水平、控制体质量的同时,不良反应发生率较低,G等位基因与T2DM易感性存在一定的相关性,而T等位基因携带者对利拉鲁肽的治疗表现出更优的效果。     

线粒体动力学与2型糖尿病和糖尿病并发症关系的研究进展

线粒体动力学即线粒体融合和分裂保持动态平衡的过程,线粒体的融合与分裂过程决定线粒体形态的可塑性。这种动态平衡的稳定是维持线粒体功能和机体功能的前提和基础,并且受多种化学酶及蛋白等因素调节。因线粒体为细胞能量代谢中心,故线粒体动力学与人类代谢性疾病的关联日益受到重视。近年来,大量研究表明,线粒体动力学失衡可以引起胰岛素抵抗和β细胞功能障碍,并且与糖尿病并发症发生密切相关。     

Evaluation of the role of CDKN2B gene in type 2 diabetes mellitus and hypertension in ethnic Saudi Arabs

Background

Coronary heart disease (CAD) is a multiple with several contributory risk traits, including type 2 diabetes and hypertension, which may share common genetic risk variants with the disease. Genome-wide association studies (GWASs) have yielded a wealth of information suggesting that CAD, the extent of contributory variants may differ according to genetic locus. The present study aimed at verifying whether the cyclin-dependent kinase 4 inhibitor B (CDKN2B) genomic region strongly associated with coronary artery disease (CAD)/myocardial infarction (MI) may also constitute risk for its risk factors type 2 diabetes mellitus (T2DM) and hypertension (HTN) in ethnic Saudi Arabs.

脂联素基因5'端调控区核苷酸多态性与2型糖尿病肾病相关性研究

研究了272名(86名非糖尿病者和186名2型糖尿病病人)深圳地区人群脂联素基因-11377C/G和-11391G/A单核苷酸多态性基因型分布及其与2型糖尿病肾病发病的相关性。结果发现-11377C/G多态性与糖尿病发病无关,-11391G/A多态性与2型糖尿病发病相关(χ2=7.662,P<0.005)。-11391基因变异和/或-11377变异可能与糖尿病早期肾病发病相关。     

那格列奈片治疗2型糖尿病的多中心随机双盲平行对照临床试验

目的　以瑞格列奈为对照,评价那格列奈治疗2型糖尿病的疗效和安全性。方法　用多中心随机双盲双模拟平行对照的试验设计,观察了228例2型糖尿病病人,其中那格列奈组111例,瑞格列奈组117例。结果　与基础值比较,治疗12周后那格列奈组空腹血糖(FBG)、餐后2h血糖(PBG)及糖化血红蛋白(HbA1c)分别下降(1.25±1.79) mmol.L-1,(4.03±2.82) mmol.L-1和(0.56±1.07)%;瑞格列奈组病人FBG、PBG及HbA1c分别下降(1.54±1.49)mmol.L-1,(3.79±3.44) mmol.L-1和(0.53±0.97)%;2组下降各指标比较均有显著性差异,而2组间比较无显著性差异。2组药物不良反应发生率比较无统计学差异。结论　那格列奈是治疗2型糖尿病有效和安全的药物。     

2型糖尿病患者大血管病变相关因素研究

目的检测2型糖尿病（T2DM）患者外源性血浆凝血因子Ⅶ（FⅦ）、内源性血浆凝血因子Ⅷ（FⅧ）、血浆纤维蛋白原（Fib）、三酰甘油（TG）等指标的水平,探讨其与糖尿病大血管病变（DMAP）的关系,为监测DMAP的发生和将来可能针对此环节实施的预防措施提供必要的理论依据。方法T2DM患者以大血管病变程度进行临床分组：重度DMAP（sDMAP）组、轻度DMAP（mDMAP）组、无DMAP（Non-DMAP）组,并设健康对照组,对4组FⅦ、FⅧ、Fib、TG水平及吸烟人数比例等指标进行比较。结果T2DM患者FⅦ、FⅧ、Fib、TG水平及吸烟人数比例高于健康对照组（P〈0.05或〈0.01）;mDMAP组和sDMAP组高于Non-DMAP组（P〈0.01或〈0.05）;sDMAP组高于mDMAP组（P〈0.05）。多因素Logistic回归分析表明FⅦ、FⅧ、Fib和TG、吸烟是DMAP的独立危险因素。结论FⅦ、FⅧ、Fib、TG水平及吸烟人数比例是T2DM及DMAP病变程度的独立危险因素。     

天津地区汉族人群E-选择素A561C基因多态性与2型糖尿病相关性研究

摘 要 目的：探讨E-选择素基因A561C多态性与天津地区汉族人群2型糖尿病（T2DM）的关系。方法：利用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）方法检测112例DM和140例正常个体A561C多态性,并进行临床资料的分析。结果：在112例DM患者中,检出12例杂合子突变基因型（AC）,C等位基因频率为5.36%;在140例对照中,检出4例AC,C为1.43%,两组均未检出突变纯合子(CC),差异有统计学意义（P＜0.05）;DM组SBP、BMI、TC、TG、LDL、FPG、P2PG、FINS高于对照组,两组差异有统计学意义（P <0.05）;以基因型分组,显示AC组FPG、 P2PG、 FINS值均高于AA组,两者间差异有统计学意义（P<0.05）。结论：C等位基因可能为天津地区汉族人群T2DM易感基因,揭示E-选择素基因多态性在DM的发生与发展中的作用。     

格列吡嗪缓释片与格列齐特治疗2型糖尿病患者的疗效比较

目的评价每日 1次服用格列吡嗪缓释片 (秦苏 )与每日 2次服用格列齐特 (达美康 )是否有相同的降糖效果。方法将 6 0例 2型糖尿病患者随机分为甲、乙两组 ,甲组用秦苏治疗 ,乙组用达美康治疗 ,治疗前后进行空腹血糖 (FPG) ,餐后 2小时血糖 (2HPG) ,糖化血红蛋白 (HbA1C)及肝、肾功能比较。结果治疗 12周后甲、乙两组的FPG、2HPG、HbA1C均有显著性下降 (P <0 .0 1) ,但组间比较差异无显著性 ,治疗前后两组的肝、肾功能均无显著性变化。结论对于无合并严重并发症的 2型糖尿病患者 ,每日 1次服用秦苏与每日 2次服用达美康有相同的降糖疗效 ,且安全性良好。     

替米沙坦对2型糖尿病大鼠心肌病变的干预研究

目的观察2型糖尿病大鼠心肌超微结构和心功能变化及替米沙坦对其的影响。方法雄性SD大鼠40只,单纯随机分为正常组（N组）、糖尿病模型组（M组）、替米沙坦干预组（T组）。M、T组大鼠高糖高脂饲料喂养4周后以25mg/kg链脲佐菌素（STZ）尾静脉1次性注射,建立2型糖尿病大鼠模型。N组常规饲料喂养4周后以等剂量的枸橼酸盐尾静脉注射。所有大鼠均以原饲料喂养。STZ注射后1周,T组给予替米沙坦8.34mg·kg^-1·d^-1,N、M组给予等量水灌胃,给药12周末结束实验,取血测空腹血糖（FBG）、空腹胰岛素（FINS）、总胆固醇（TC）、三酰甘油（TG）;制备电镜切片,监测心功能。结果M、T组血INS、TG均显著高于N组（P〈0.01）,T组INS、TG显著低于M组（P〈0.01）。结论替米沙坦能够改善糖尿病心肌病,机制可能与降低INS、TG有关。     

微粒化非诺贝特治疗2型糖尿病患者高脂血症

目的:观察微粒化非诺贝特对2型糖尿病患者高脂血症的治疗作用.方法:采用自身对照的方法,21例入选病例用微粒化非诺贝特200mg qn,连续服用8wk,治疗期间降糖药物不变.结果:微粒比非诺贝特治疗4wk,就可见TC降低14.7%,TG降低35.8%,TC/HDL-C降低18.5%;8wk时更为明显,分别降低22%、44.9%和27%(P0.05);微粒化非诺贝特对HDL-C、ApoA_1、和ApoB无影响.微粒化非诺贝特治疗8wk对肝肾功能、血尿常规、体重等均无明显影响.结论:微粒化非诺贝特是治疗2型糖尿病高脂血症效果好、不良反应较小的治疗高脂血症的药物.     

The influence of kidney function on dapagliflozin exposure,metabolism and pharmacodynamics in healthy subjects and in patients with type 2 diabetes mellitus

Aim(s)

This study assessed the effect of differences in renal function on the pharmacokinetics and pharmacodynamics of dapagliflozin, a renal sodium glucose co-transporter-2 (SGLT2) inhibitor for the treatment of type 2 diabetes mellitus (T2DM).

Methods

A single 50 mg dose of dapagliflozin was used to assess pharmacokinetics and pharmacodynamics in five groups: healthy non-diabetic subjects; patients with T2DM and normal kidney function and patients with T2DM and mild, moderate or severe renal impairment based on estimated creatinine clearance. Subsequently, 20 mg once daily multiple doses of dapagliflozin were evaluated in the patients with T2DM. Formation rates of dapagliflozin 3-O-glucuronide (D3OG), an inactive metabolite, were evaluated using human isolated kidney and liver microsomes.

Results

Plasma concentrations of dapagliflozin and D3OG were incrementally increased with declining kidney function. Steady-state C_max for dapagliflozin were 4%, 6% and 9% higher and for D3OG were 20%, 37% and 52% higher in patients with mild, moderate and severe renal impairment, respectively, compared with normal function. AUC(0,τ) was likewise higher. D3OG formation in kidney microsomes was three-fold higher than in liver microsomes and 109-fold higher than in intestine microsomes. Compared with patients with normal renal function, pharmacodynamic effects were attenuated with renal impairment. Steady-state renal glucose clearance was reduced by 42%, 83% and 84% in patients with mild, moderate or severe renal impairment, respectively.

Conclusions

These results indicate that both kidney and liver significantly contribute to dapagliflozin metabolism, resulting in higher systemic exposure with declining kidney function. Dapagliflozin pharmacodynamics in diabetic subjects with moderate to severe renal impairment are consistent with the observation of reduced efficacy in this patient population.     

胰岛素联合罗格列酮治疗2型糖尿病患者疗效观察

目的比较胰岛素联合罗格列酮和单用胰岛素治疗2型糖尿病（T2DM）患者的疗效。方法将120例T2DM患者分成治疗组（胰岛素加罗格列酮）与对照组（胰岛素治疗），随访观察12周。结果2组患者治疗后血糖均得到良好控制，但治疗组胰岛素日需求量明显低于对照组（P〈0．01）；与对照组相比，治疗组血甘油三酯下降，而高密度脂蛋白胆固醇升高（P〈0．05），B细胞功能指数升高（P〈0．05），胰岛素抵抗指数显著降低（P〈0．05），脂联素水平升高（P〈0．01）。结论罗格列酮与胰岛素联用能使2型糖尿病患者血糖、血脂改善，增加胰岛素敏感性，降低胰岛素抵抗，升高脂联素水平，优于单用胰岛素治疗。     

初诊2型糖尿病患者胰高血糖素水平的变化及临床意义

目的探讨初诊断2型糖尿病胰高血糖素水平的变化和其与胰岛素抵抗的关系。方法98例初诊断2型糖尿病患者和20例血糖正常的健康人,分别为糖尿病组和正常对照组,两组患者均行标准馒头餐试验,分别测定餐前0min和餐后30、60、120rain时点的血糖、胰岛素和胰高血糖素水平。结果（1）糖尿病组餐前0rain和餐后30、60、120rain的胰高血糖素水平与正常对照组对应的各时点比较,均显著增高,两组间差异有统计学意义。（2）糖尿病组餐后各时点胰高血糖素水平与胰岛素抵抗指数HOMA-IR相关。结论胰高血糖素分泌紊乱是2型糖尿病患者发生高血糖的重要因素,胰岛α细胞存在胰岛素抵抗。