The Influence of the Pro12Ala Mutation of PPARγ2 Receptor Gene on β-cells Restoration and Insulin Resistance in Type 2 Diabetes with Hypertension

Type2diabetes(T2DM)isageneraldiseasesduetobothgeneticandenvironmentalfactors[1],andT2DMissusceptibletohypertension(HP).Clinicalandexperimentalstudieshaveindicatedthatinsulinresistanceandhyperinsulinemiaareim portantfactorsresultingindiabetesandhyperten sion.Therefore,geneticfactorscontributealottoT2DMwithhypertension.Uptonow,moststudiesconcerningtheasso ciationbetweenthismutationandsomecomplextraits,suchasobesity,insulinresistanceandT2DM,showedthattheX12Ala(eitherPro12AlaorAla12Ala)gen…     

Chemerin and apelin are positively correlated with inflammation in obese type 2 diabetic patients

Background  As two novel adipocytokines, chemerin and apelin play a key role in the pathological process of insulin resistance (IR), glucose metabolism and obesity, researchers have found that the levels of chemerin and apelin changed significantly in type 2 diabetic patients with obesity, however, the underlying mechanism involved remains unclear. The aim of this study was to investigate whether chemerin and apelin play an important role in the pathophysiologic proceeding of diabetes.

Methods  This study enrolled 81 newly diagnosed obese type 2 diabetes mellitus (T2DM) patients (T2DM group, n=81). All the patients were randomly assigned to DM1 group treated with metformin (n=41) and DM2 group treated with pioglitazone (n=40). After hypoglycemic agents treatment, patients under better blood glucose control were chosen to be given antioxidant treatment. Another 79 subjects without T2DM were recruited as normal control group (NC group), including 40 subjects (NC1 group) with normal body mass index (BMI) and 39 obese subjects (NC2 group). Levels of chemerin, apelin, BMI, tumor necrosis factor-α (TNF-α), homeostasis model assessment of IR (HOMA-IR) and 8-isoprotaglandim F2α (8-iso-PGF2α) were examined at baseline and post-treatment. The relationship between chemerin, apelin and BMI, TNF-α, HOMA-IR, 8-iso-PGF2α was analyzed.

Results  The baseline levels of chemerin, apelin, TNF-α, HOMA-IR and 8-iso-PGF2α in T2DM group were significantly higher than normal control group (P <0.001). All indices mentioned above were significantly decreased after treatment (P <0.05). In T2DM patients treated with pioglitazone, indices mentioned above except for HOMA-IR, were decreased significantly compared with patients treated with metformin (P <0.05). After antioxidant treatment using lipoic acid, levels of chemerin, apelin, TNF-α and 8-iso-PGF2α were further significantly decreased (P <0.05). Correlation analysis showed that the levels of chemerin and apelin correlated positively with BMI, TNF-α, HOMA-IR and 8-iso-PGF2α before and after treatment with hypoglycemic agents (P <0.01). The levels of chemerin and apelin also had positive correlation with TNF-α and 8-iso-PGF2α after antioxidant treatment (P <0.05).

Conclusions  The levels of chemerin and apelin in obese T2DM patients are closely related to IR. The increased levels may be a result of compensatory response to IR, and also may be the causative factor of IR. The levels of chemerin and apelin correlate closely with oxidative stress and inflammation. The two adipokines may be inflammatory factors playing important roles in the initiation and development of obese T2DM. Chemerin and apelin are related to the pathophysiology of IR, oxidative stress and inflammation.

     

Inhibitory effects of high glucose/insulin environment on osteoclast formation and resorption in vitro

Patients with type 2 diabetes mellitus (T2DM) exhibit hyperglycemia and hyperinsulinemia and increased risk of fracture at early stage, but they were found to have normal or even enhanced bone mineral density (BMD). This study was aimed to examine the molecular mechanisms governing changes in bone structure and integrity under both hyperglycemic and hyperinsulinemic conditions. Monocytes were isolated from the bone marrow of the C57BL/6 mice, induced to differentiate into osteoclasts by receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) and exposed to high glucose (33.6 mmol/L), high insulin (1 μmol/L), or a combination of high glucose/high insulin (33.6 mmol/L glucose and 1 μmol/L insulin). Cells cultured in α-MEM alone served as control. After four days of incubation, the cells were harvested and stained for tartrate resistant acid phosphatase (TRAP). Osteoclast-related genes including RANK, cathepsin K and TRAP were determined by using real-time PCR. The resorptive activity of osteoclasts was measured by using a pit formation assay. Osteoclasts that were derived from monocytes were of multinucleated nature and positive for TRAP, a characteristic marker of osteoclasts. Cell counting showed that the number of osteoclasts was much less in high glucose and high glucose/high insulin groups than in normal glucose and high insulin groups. The expression levels of RANK and cathepsin K were significantly decreased in high glucose, high insulin and high glucose/high insulin groups as compared with normal glucose group, and the TRAP activity was substantially inhibited in high glucose environment. The pit formation assay revealed that the resorptive activity of osteoclasts was obviously decreased in high glucose group and high glucose/high insulin group as compared with normal group. It was concluded that osteoclastogenesis is suppressed under hyperglycemic and hyperinsulinemic conditions, suggesting a disruption of the bone metabolism in diabetic patients.     

The mutation of insulin receptor substrate-1 gene in Chines e patients with non-insulin-dependent diabetes mellitus

Objective To identify the relationship between mutation in the insulin receptor substrate-1 (IRS-1) gene and the incidence of non-insulin-dependent diabetes mellitus (NIDDM) in the Chinese population. Methods Samples were obtained from 68 Chinese patients with NIDDM and 68 control subjects. The +1700～+4437 bp fragment of the IRS-1 gene was screened by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. All SSCP variations were submitted to DNA sequence analysis. Results Two amino acid variations ［GGG →AGG(G(971) R) and CCT→TCT(P(1079) S)］ and 3 silent mutations ［GAT→GAC(D(422) D), CCA→CCC(P(737) P) and GCA→GCG(A(804) A)］ were identified, among which the CCA→CCC(P(737) P) and CCT→TCT(P(1079) S) have not been previously reported. All five variations were found in Chinese patients with NIDDM, while GCA→GCG(A(804) A) was the only one found in control subjects. The overall incidence of the five variations in Chinese patients with NIDDM were much higher than that in control subjects (38.2% vs 7.4%, χ(2)=18.42,P&lt;0.01). The most common polymorphism in the Chinese population was GCA→GCG(A(804) A), and its frequency was significantly higher in Chinese patients with NIDDM than in controls (26.5% vs 7.4%, χ(2)=8.84,P&lt;0.01). The homozygotes of the variation in patients with NIDDM and control subjects were 8.8% and 1.5%, respectively (χ(2)=2.41,P&gt;0.05). Conclusion These results indicate that there may be a relation between these nucleotide variations of IRS-1 gene and Chinese patients with NIDDM     

Switching from human insulin to biphasic insulin aspart 30 treatment gets more patients with type 2 diabetes to reach target glycosylated hemoglobin <7%: the results from the China cohort of the PRESENT study

Background The clinical importance of glycaemic control in patients with diabetes has been well established. This study aimed to explore twice-daily biphasic insulin aspart 30 （BIAsp 30） for insulin initiation in patients with type 2 diabetes mellitus （T2DM） who had poor glycaemic control with human insulins （His）. We use data from a Chinese cohort of the PRESENT study.Methods In the 3-month study, Chinese subjects with T2DM started insulin therapy with BIAsp 30 in routine care. Glycaemic control was measured by glycosylated hemoglobin （HbA1c）, fasting plasma glucose （FPG） and posting plasma glucose （PPG）. The safety assessment included hypoglycaemia and other adverse events.Results A total of 1989 subjects previously treated with His were switched to BIAsp 30 for 3-month treatment. Mean HbA1c, FPG and PPG were significantly improved after the therapy. The overall rate of hypoglycaemia decreased at the end of the trial except for the patients previously treated with long-acting insulin. Most of the events were minor and diurnal hypoglycaemia. Only one serious adverse drug reaction （SADR）, a local hypersensitivity, was reported. The majority of the patients （296.7%） and physicians （≥84.7%） were either satisfied or very satisfied with the treatment using BIAsp 30 compared with previous HI therapy.Conclusion The BIAsp 30 treatment improved both glycaemic control and patients＇ satisfaction without increasing hypoglycaemia in T2DM subjects inadequately controlled by Hls.     

TCF7 L2基因单核苷酸多态性与2型糖尿病研究现状

2型糖尿病（type 2 diabetes mellitus,T2DM）是一种具有明显异质性的多基因遗传病,又称为复杂性疾病（ complex disease）,胰岛素抵抗（insulin resistance,IR）或胰岛素分泌相对不足而引起慢性高血糖构成其发病主要原因。 T2DM受环境、遗传、饮食、种族、年龄、生活方式等多种因素的影响,而遗传因素在其发生发展中起着重要作用。2006年Grant等首次发现了核转录因子7类似物2（variant of transcrip-tion factor 7 like 2, TCF7L2）基因的微卫星 DG10S478与T2DM显著相关,更多的相关研究陆续展开,并得出一致结论：TCF7L2是 T2DM 发生高度相关的易感基因。本文就TCF7L2基因SNPs与T2DM相关性研究现状进行综述。     

糖尿病患者合并急性心肌梗塞的临床特点及预后分析

目的　探讨糖尿病 (DM )合并急性心肌梗塞 (AMI)的临床特点及预后。方法　回顾性分析 90例AMI患者的临床资料 ,比较DM并AMI(DM组 )和非DM的AMI(非DM组 )患者的临床特点和预后。结果　DM组发生多部位梗塞明显多于非DM组 (χ2 =4.18,P <0 .0 5 ) ,DM组发生AMI时并发症的发生率及病死率明显高于非DM组 (P <0 .0 5或 0 .0 1) ,主要死于心力衰竭、室颤。结论　DM合并AMI患者心力衰竭发生率高 ,病情较重 ,病死率高。     

252例糖尿病患者入院原因分析

目的了解糖尿病(DM)患者入院主要原因,为糖尿病(DM)患者并发症防治及减少入院次数提供资料。方法选择2011年7月-2012年7月内分泌科的DM住院病人为研究对象,共收集病历资料252例,以入院时主诉症状及入院诊断为主,统计分析各年龄段DM患者主要住院原因。结果 DM患者的入院原因:第1组(20～40岁)前3位:DM酮症酸中毒(64%)、代谢综合征(20%)、高血糖症候群(16%);第2组(40～60岁)前3位:DM慢性并发症(37.04%)、高血糖症候群(22.22%)、DM酮症酸中毒(14.82%);第3组(≥60岁)前3位:DM慢性并发症(43.33%)、感染(16.67%)、低血糖(16.67%)。结论 DM慢性并发症为中老年DM患者入院的主要原因。     

糖尿病合并肺结核临床特点探讨

目的探讨糖尿病(DM)合并肺结核(LTB)患者临床特点。方法对50例DM合并LTB患者(DM组)与同期住院64例非DMLTB患者(非DM组)的临床资料进行比较分析。结果DM组无呼吸道症状和病情属重度的比例均高于非DM组(P<0.05),DM组空洞发生率显著高于非DM组(P<0.01)。结论DMLTB患者缺乏呼吸道症状的比例和空洞发生率高,病灶范围大,病情重。     

糖尿病合并MAFLD患者外周血Chemerin与糖脂代谢、内脏脂肪、氧化应激及炎症指标的关系

目的 探究糖尿病(diabetes mellitus,DM)合并代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)患者外周血Chemerin与糖脂代谢、内脏脂肪、氧化应激及炎症指标的关系.方法 选取DM患者(DM组)84例,DM合并MAFLD患者(DM合并...     

男性2型糖尿病患者血Ghrelin与骨密度的关系

目的:研究男性2型糖尿病(T2DM)患者血Ghrelin与骨密度(BMD)的关系.方法:57例男性T2DM患者,合并骨质疏松(OP)组23例(DM1 组) 、骨含量正常组34例(DM2 组),健康男性对照组15例(N组),测血清Ghrelin,并测量腰椎和股骨BMD.结果:(1)DM1、DM2组与N组比较, Ghrelin的水平差异有统计学意义(P＜0.05);(2)DM1、DM2组Ghrelin水平无明显差异(P＞0.05);(3)DM1、DM2组中Ghrelin与股骨BMD、椎骨BMD均无关(P＞0.05).结论:T2DM合并OP患者血液中Ghrelin水平与股骨BMD、椎骨BMD间无相关性.     

糖尿病合并冠心病急性心肌梗死的临床观察

目的:探讨糖尿病(DM)合并急性心梗(AMI)的临床特点及预后。方法:分析80例AMI患者临床资料比较DM并AMI(DM组)和非DM的AMI(非DM组)患者的临床特点和预后。结果:DM组发生大部分梗塞明显多于非DM组,DM组发生AMI时并发症的发生率及死亡率明显高于非DM组。(P<0.05或0.01),主要死因心衰,室颤,心源性休克。结论:DM合并AMI患者心衰发生率高,并发症多,病情重,死亡率高。     

胰高血糖素刺激试验在糖尿病患者中的临床鉴别诊断意义探讨

目的:为了探寻鉴别1型糖尿病(DM1)和2型糖尿病(DM2)的新方法。方法:应用放射免疫法测定DM1组、DM2组和正常对照组空腹和胰高血糖素刺激后6min血清C肽水平。结果:空腹血清C肽水平:DM1组比正常对照组低(P<0.005)、DM1组与DM2组、DM2组与正常对照组虽有差异,但无统计学意义(P>0.05)。胰高血糖刺激后6分钟C肽水平:DM1组比正常对照组和DM2组均低(P<0.01),DM2组与正常对照组差异无统计学意义(P>0.05)。C肽增加百分率:DM1组比正常对照组低(P<0.05),比DM2组亦低,但无统计学意义(P>0.05),DM2组与正常对照组无统计学差异(P>0.05)。结论:胰高血糖素刺激后C肽测定有助于鉴别DM1和DM2。     

糖尿病患者尿微量白蛋白与冠心病的关系

目的探讨尿微量白蛋白(mAlb)与2型糖尿病(diabetes mellitus type 2,T2DM)合并冠心病(CHD)的相关性。方法选择临床确诊的住院和门诊T2DM患者151例,分为T2DM组(76例)和T2DM合并CHD组(75例),测定尿mAlb或尿mAlb排泄率(UAER)以及生化项目,进行对比分析。结果①T2DM CHD组患者FPG2、hPG、TC和LDL-C水平显著高于T2DM组和正常对照(NC)组(P<0.05);HDL-C水平显著低于T2DM组和NC组(P<0.05)。②T2DM CHD组患者尿mAlb水平显著高于T2DM患者和NC组(P<0.05),且阳性率也显著高于T2DM患者和NC组(P<0.05)。③T2DM尿mAlb阳性患者57.5%(61/106)合并CHD,阴性患者33.1%(14/45)合并CHD,两者相差显著(χ2=8.832,P<0.05)。结论T2DM合并CHD患者有更严重的代谢紊乱和高水平的尿mAlb,高水平的尿mAlb T2DM患者易并发CHD。     

糖尿病合并脑白质疏松症患者事件相关电位分析

目的观察糖尿病(DM)合并脑白质疏松症(LA)患者认知功能事件相关电位P300、N400的特征。方法对217例DM合并LA患者(DM合并LA组)、55例单纯DM患者(DM组)和30例健康志愿者(对照组)进行P300、N400、失配性负波(MMN)检测和简易精神状态检查量表(MMSE)检查,并对结果进行比较。结果 DM组和DM合并LA组患者MMSE评分显著低于对照组(P<0.05,P<0.01),DM合并LA组患者MMSE评分显著低于DM组(P<0.01)。与对照组比较,DM组和DM合并LA组患者事件相关电位P300、MMN和N400潜伏期显著延长(P<0.05,P<0.01),波幅显著降低(P<0.05,P<0.01);与DM组比较,DM合并LA组患者事件相关电位P300、MMN和N400潜伏期显著延长(P<0.01),波幅显著降低(P<0.05)。随着脑白质损害程度的加重,事件相关电位P300和N400潜伏期显著延长(P<0.01),波幅显著降低(P<0.01)。结论事件相关电位P300、N400检测可客观评价DM合并LA患者的认知功能。     

生长激素瘤并发糖尿病患者胰岛素抵抗的临床观察（附23例报告）

生长激素瘤使膜化骨形成增加致骨增宽增厚，若高垂体生长激素（ GH）血症发生于骨骺关闭以后，则长骨不能延长，但骨量相对增加，骨骼增宽增厚，表现为特殊的外貌。临床上以骨关节症状为常见。垂体生长激素瘤（ growth hormone tumor；GH瘤）与糖代谢密切相关，垂体瘤分泌GH过多，有导致糖尿病（ diabetes mellitns ， DM ）的倾向。国外报道其DM的发生率在24％～50％［1，2］，是较常见的继发性DM之一。现总结我院2007年1月至2011年1月收治的42例GH瘤患者，合并DM者23例。结合临床表现，观察治疗前后血糖指标及其胰岛素敏感性指数变化。探讨GH瘤患者与胰岛素抵抗（ insulin resistance ，IR）的关系。     

糖尿病合并急性心肌梗死36例临床分析

目的　探讨糖尿病 (DM )合并急性心肌梗死 (AMI)的临床特点及预后。方法　回顾性分析DM合并AMI患者的临床资料 ,比较DM合并AMI(DM组 )和非DM的AMI(NDM组 )的临床特点及预后。结果　DM组发生多部位梗死明显多于NDM组 (P <0 .0 1) ,DM组患者无痛性AMI发率高 (占 3 0 .5% ) ,DM组发生AMI时并发症及死亡率明显高于NDM组 (P <0 .0 1)。结论　DM合并AMI患者临床症状不典型 ,死亡率高     

2型糖尿病患者左室肥厚及颈动脉粥样硬化与胰岛素抵抗

目的:探讨胰岛素抵抗(IR)对2型糖尿病(172DM)患者左室肥厚(LVH)及颈动脉粥样硬化的作用.方法:对39例正常对照者,102例T2DM患者,30例2型糖尿病合并左室肥厚患者(T2DM LVH组),32例2型糖尿病合并颈动脉内膜中层增厚患者(172DM IMT组),23例2型糖尿病合并颈动脉斑块患者(T2DM CAP组),用稳态模式评估法(HOMA-IR)评价IR.结果:T2DM组、T2DM LVH组、T2DM IMT组、T2DM CAP组的HOM-IR均比对照组高(P＜0.05),T2DM LVH组,T2DM IMT组,T2DM CAP组HOMA-IR比单纯T2DM组高(P＜0.05),T2DM CAP组的HOMA-IR比T2DM IMT组稍高,但无显著性差异(P＞0.05).结论:IR对T2DM患者合并LVH、颈动脉粥样硬化有影响.     

2型糖尿病伴非酒精性脂肪肝患者血清 nesfatin-1水平的变化

目的：观察2型糖尿病(T2DM)伴或不伴非酒精性脂肪肝(NAFLD)患者血清 nesfatin-1水平的变化。方法检测T2DM 组(211例,其中 T2DM 不伴 NAFLD 组98例,T2DM 伴 NAFLD 组113例)和对照组(NGT)组(75例)的空腹血清 nesfa-tin-1水平,同时测定身高、体质量、血糖(GLU)、血脂谱、胰岛素水平(INS)、糖化血红蛋白(HbA1c)、谷丙转氨酶水平(ALT),计算BMI、胰岛素抵抗指数(HOMA-IR)。结果T2DM 组血清 nesfatin-1水平均明显高于 NGT 组(P <0.05),T2DM 组中 T2DM 伴NAFLD 亚组血清 nesfatin-1水平高于 T2DM 不伴 NAFLD 组(P <0.05)。T2DM 组 nesfatin-1与病程中度相关(r=-0.477,P <0.05)T2DM 组中脂肪肝的发生与 BMI、TG、nesfatin-1有关(P <0.05)。结论nesfatin-1可能参与 T2DM 及 NAFLD 的发生。     

冠心病合并2型糖尿病患者冠状动脉病变特点

目的 探讨冠心病合并2型糖尿病(T2DM)患者冠状动脉病变特点及相关危险因素,以及T2DM对冠状动脉病变的影响.方法 2003年12月至2008年2月行冠状动脉造影确诊为冠心病的患者324例,按有无T2DM分为T2DM组82例,非DM组242例,比较2组之间的相关临床因素及冠状动脉造影情况、治疗情况.结果 (1)T2DM组与非DM组比较,胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(IDL)、体重指数(BMl)差异有统计学意义(P<0.05),T2DM组除HDL外其余指标均高于非DM组.T2DM组高血压、心肌梗死发生率高于非DM组(P<0.05).(2)T2DM组病变血管支/例、多支病变、弥漫病变、血管中重度狭窄病变发生率均高于非DM组(P<0.05).结论 T2DM发生冠心病常与高血压、脂代谢紊乱和/或肥胖等因素同时存在,其冠状动脉病变程度加重,多支病变、弥散病变、心肌梗死等危险心脏事件发生率高.