2型糖尿病合并脂肪肝患者的临床特征分析

近年来,非酒精性脂肪肝（NAFL）的发病率逐渐升高,在2型糖尿病（DM）患者中其发病率约为50%.NAFL可进展为非酒精性脂肪性肝炎（脂肪肝合并炎症、坏死或纤维化）、肝硬化、甚至可发展为终末期肝病和肝细胞癌.NAFL已成为危害人们健康的常见病.本文对初诊2型DM合并脂肪肝患者的临床特征做一分析,旨在探讨2型DM患者脂肪肝的易患因素,以利于脂肪肝的预防和治疗.     

基于CT诊断肌少症与老年2型糖尿病伴骨质疏松的相关性

目的 探究基于CT诊断肌少症与老年2型糖尿病(T2DM)伴骨质疏松(OP)的相关性。方法 纳入T2DM合并OP患者171例。根据CT测量的骨骼肌指数(SMI)分为OP+T2DM+肌少症组及OP+T2DM+非肌少症组,分析影响T2DM合并OP患者出现肌少症的危险因素,并分析血糖指标及骨密度T值对肌少症严重程度的评估价值及与SMI值的相关性。结果 OP+T2DM+肌少症组腰臀比、体重指数(BMI)、骨密度T值小于OP+T2DM+非肌少症组,糖化血红蛋白(HbA1c)、尿白蛋白/肌酐比值(UACR)值大于OP+T2DM+非OP+T2DM+肌少症组,合并非酒精性脂肪性肝炎人数比例及空腹血糖(FPG)、胱抑素C水平高于OP+T2DM+非肌少症组,25羟基维生素D(25-OH-D)、总胆固醇水平低于OP+T2DM+非肌少症组,差异均有统计学意义(P<0.05);合并非酒精性脂肪性肝炎、FPG≥9.56 mmol/L、HbA1c≥8.70%、UACR≥53.47 mg/g、25-OH-D<15.04 ng/ml、骨密度T值≤-2.5 S是影响老年T2DM伴OP出现肌少症的危险因素(P&l...     

非酒精性脂肪性肝病合并2型糖尿病患者肝组织病理学变化研究

目的 研究非酒精性脂肪性肝病（NAFLD）合并2型糖尿病（T2DM）患者肝脏组织病理学变化。方法 分析240例行肝活检术的NAFLD患者临床资料,比较NAFLD合并T2DM与未合并T2DM患者肝组织病理学表现和评分的差异。结果 在240例NAFLD患者中,合并2型糖尿病者80例（33.3%）,未合并T2DM 者160例（66.7%）;在NAFLD合并T2DM患者中非酒精性脂肪性肝炎（NASH）60例、肝纤维化20例,未合并T2DM患者中分别为68例和92例;在NAFLD合并T2DM患者中检出肝纤维化评分≥2者30例（37.5%）、肝细胞气球样变评分≥2者23例（28.8%）和马洛里小体22例（27.5%）,均显著高于未合并T2DM患者的【20例（12.5%）、22例（13.8%）和30例（18.8%）,P<0.05】;T2DM为发生NASH（OR=3.27,95%CI：1.42~7.55）和肝纤维化（OR=3.35,95%CI：1.55~7.63）的独立危险因素。结论 合并T2DM的NAFLD患者肝组织病理学损伤更趋严重,应注意防治。     

老年2型糖尿病合并非酒精性脂肪性肝病患者Vaspin水平的变化

目的研究老年T2DM合并非酒精性脂肪性肝病（NAFLD）患者血清Vaspin水平的变化及其临床意义。方法测定老年T2DM合并NAFLD患者44例（T2DM＋NAFLD组）,老年T2DM不合并NAFLD患者40例（T2DM组）,老年糖耐量正常的NAFLD患者40例（NAFLD组）与老年正常对照41名（NC组）的Vaspin水平。结果T2DM＋NAFLD组、T2DM组、NAFLD组血清Vaspin水平均明显高于NC组（1．46±0．43、1．03±0．27、0．76±0．28vs0．36±0．13）ng／ml,差异有统计学意义（P〈0．01或P％0．05）。多元逐步回归分析显示Fins、内脏脂肪厚度（VFT）、HbA1c是Vaspin水平的独立影响因素,Vaspin、VFT和TG是老年T2DM合并NAFLD的危险因素。结论血清Vaspin水平的变化可能在老年T2DM合并NAFLD的发生发展中起一定作用。     

塞来昔布对实验性糖尿病大鼠早期视网膜病变的影响

目的研究塞来昔布对糖尿病（DM）大鼠视网膜血管内皮生长因子（VEGF）表达及视网膜超微结构的影响。方法将40只Wistar大鼠用链脲佐菌素（STZ）腹腔注射制成DM大鼠模型,随机分成DM组（n=20）和塞来昔布灌胃组（n=20）。另15只正常大鼠为正常对照组。3个月后处死全部大鼠,取视网膜进行透射电镜观察,应用免疫组化检测视网膜VEGF蛋白表达。结果塞来昔布灌胃组视网膜内皮细胞、神经节细胞凋亡较DM组明显减轻。正常对照组视网膜VEGF免疫组化反应阳性弱,VEGF蛋白表达量低;DM组视网膜VEGF免疫组化反应呈强阳性,VEGF蛋白表达增高（P〈0.01）;塞来昔布灌胃组VEGF免疫组化反应阳性减弱,VEGF蛋白表达降低（P〈0.01）。结论塞来昔布能够抑制STZ诱导的DM大鼠视网膜VEGF蛋白表达,并减轻视网膜超微结构损害。     

T2DM合并腔隙性脑梗塞80例分析

对T2DM合并LI的病人80例进行回顾性分析（DM组），以同期非糖尿病合并（I）病人50例为对照（非DM组）。结果：DM组冠心病的患病率显著增多（P〈0．01）。两组高血压发病率均增高，比较无差异（P〉0．05）。而血脂及纤维蛋白原增高较正常有显著性差异（P〈0．05）。结论：高血糖是T2DM合并LI塞的独立危险因素，并及冠心病患病率明显高于高血压、高纤维蛋白原、甘油三脂、胆固醇是两组脑梗塞病人的共同危险因素。     

T2DM合并腔隙性脑梗塞80例分析

对T2DM合并LI的病人80例进行回顾性分析（DM组），以同期非糖尿病合并（I）病人50例为对照（非DM组）。结果：DM组冠心病的患病率显著增多（P〈0．01）。两组高血压发病率均增高，比较无差异（P〉0．05）。而血脂及纤维蛋白原增高较正常有显著性差异（P〈0．05）。结论：高血糖是T2DM合并LI塞的独立危险因素，并及冠心病患病率明显高于高血压、高纤维蛋白原、甘油三脂、胆固醇是两组脑梗塞病人的共同危险因素。     

非肥胖的2型糖尿病合并脂肪肝的危险因素分析

将非肥胖的T2DM患者按是否合并脂肪肝分为A组（无脂肪肝组）和B组（脂肪肝组）,测定血压、ALT、AST、TC、TG、HDL、LDL、FBG、FINS、FCP和HbA1c,计算BMI、Homa-IR。结果糖尿病合并脂肪肝组ALT、TG高于无脂肪组（P〈0．05）,HDL低于无脂肪肝组（P〈0．05）;高TG、高INS及低HDL是非肥胖T2DM合并脂肪肝的危险因素。结论脂质异常及高胰岛素血症是导致非肥胖T2DM人发生脂肪肝的危险因素。     

2型糖尿病合并非酒精性脂肪肝患者血清hs-CRP与IMT的关系

目的探讨2型糖尿病（T2DM）合并非酒精性脂肪肝（NAFLD）患者血清高敏C反应蛋白（hs-CRP）与颈动脉内中膜厚度（IMT）的相关性。方法将340例T2DM患者根据是否合并NAFLD分为T2DM无NAFLD（DM-A）组、T2DM合并NAFLD（DM-B）组,采用免疫比浊法测定血清hs-CRP水平、彩色多普勒超声仪测量IMT厚度,并与正常对照组进行比较。结果与对照组、DM-A组比较,DM-B组随hs-CRP水平增高,IMT逐渐增厚。hs-CRP水平与IMT呈正相关（r=0.137,P〈0.05）,亦与NAFLD存在关联（OR=2.104,P〈0.05）。结论 T2DM合并NAFLD患者血清hs-CRP与NAFLD、IMT关系密切,易出现大血管病变。     

胰岛素抵抗与2型糖尿病合并非酒精性脂肪肝关系的研究

研究胰岛素抵抗与2型糖尿病（T2DM）合并非酒精性脂肪肝（NAFL）的关系,发现T2DM伴有脂肪肝组BMI、WHR、TC、TG、血尿酸、丙氨酸氨基转移酶、γ-谷氨酰转移酶和HOMA-IR较T2DM不伴脂肪肝组升高（P均〈0．01）;Logistic回归分析表明,HOMA—IR、TC、TG、WHR是NAFL形成的独立危险因素。     

TCF7L2多态性与2型糖尿病关系的研究进展

2型糖尿病是一种多基因遗传病,多个微效基因的累加作用造成携带致病基因个体对糖尿病的遗传易感性。转录因子7类似物2（TCF7L2）是继过氧化物酶体增殖物激活受体扎KCNJ11等之后被确认的又一个2型糖尿病易感基因,其危险等位基因是迄今发现的与2型糖尿病的发生关联最强的变异,常见危险位点为rs7903146和rs12255372。TCF7L2属于核受体家族,间接介导Wnt信号传导通路。TCF7L2变异个体的表型为糖刺激后胰岛素分泌不足,但其增加2型糖尿病发病风险的机制尚未明确。     

Functional dissection of the interactions of stonin 2 with the adaptor complex AP-2 and synaptotagmin

Synaptic vesicle recycling is in part mediated by clathrin-mediated endocytosis. This process involves the coordinated assembly of clathrin and adaptor proteins and the concomitant selection of cargo proteins. Here, we demonstrate that the endocytotic protein stonin 2 localizes to axonal vesicle clusters through its micro-homology domain. Interaction of this domain with synaptotagmin I is sufficient to recruit stonin 2 to the plasmalemma. The N-terminal domain of stonin 2 harbors multiple AP-2-interaction motifs that bind to the clathrin adaptor complex AP-2. These motifs with the consensus sequence WVxF are capable of binding to the alpha-adaptin ear domain and to micro2. Mutation of the tyrosine motif-binding pocket of micro2 abolishes recognition of the WVxF peptide, suggesting that association with stonin 2 renders AP-2 incompetent to sort tyrosine motif-containing cargo proteins. We hypothesize that stonin 2 may function as an AP-2-dependent sorting adaptor for synaptic vesicle recycling.     

Polymorphisms of the insulin receptor substrate-2 in patients with type 2 diabetes

We investigated the significance of Gly1057Asp and Leu647Val insulin receptor substrate (IRS)-2 polymorphisms in two Italian cohorts comprising 186 glucose-tolerant subjects and 240 subjects with type 2 diabetes from the Lazio region (i.e. representative of central Italy), and 123 glucose-tolerant subjects from the Sicily region (i.e. representative of south Italy). The allelic frequency of Gly1057Asp variant did not differ between diabetics (32.9%) and nondiabetic subjects, whatever their ethnicity was (35.8% and 33.7% from Lazio and Sicily, respectively). As compared with Gly/Gly subjects within each group, Asp/Asp individuals showed no differences in quantitative traits, including fasting insulin and C-peptide, and several indices of insulin sensitivity and secretion. Only one of the diabetic patients was heterozygous for the Leu647Val variant, and none of the control subjects carried this variant. This patient had three children who were also heterozygous for this variant. They were glucose tolerant, and their insulin sensitivity and insulin secretion indices were within the range of age-matched controls. We also analyzed IRS-2 function in fibroblasts from carriers of Gly1057Asp or Leu647Val variant. No defects in IRS-2 expression, insulin-stimulated phosphorylation, or binding to the p85 subunit of phosphatidylinositol 3-kinase were observed. These results strongly argue against a major role of IRS-2 polymorphisms in the pathogenesis of type 2 diabetes.     

解偶联蛋白2基因多态性与2型糖尿病的相关性

天津地区汉族人群中,解偶联蛋白(UCP)2启动子-866G/A基因多态性与2型糖尿病发病无明显相关性,但与葡萄糖刺激胰岛素分泌功能相关。     

Mdm2 facilitates the association of p53 with the proteasome

The ubiquitin ligase Mdm2 targets the p53 tumor suppressor protein for proteasomal degradation. Mutating phosphorylation sites in the central domain of Mdm2 prevents p53 degradation, although it is still ubiquitylated, indicating that Mdm2 has a post-ubiquitylation function for p53 degradation. We show that Mdm2 associates with several subunits of the 19S proteasome regulatory particle in a ubiquitylation-independent manner. Mdm2 furthermore promotes the formation of a ternary complex of itself, p53, and the proteasome. Replacing phosphorylation sites within the central domain with alanines reduced the formation of the ternary complex. The C-terminus of Mdm2 was sufficient for interaction with the proteasome despite an additional proteasome binding site in the Mdm2 N-terminus. In addition to binding to the proteasome, the C-terminus of Mdm2 bound to the central domain, possibly competing with, and therefore blocking, Mdm2/proteasome interaction. We propose that Mdm2 facilitates, or at least enhances, the association of p53 with the proteasome and that phosphorylation of the central domain of Mdm2 regulates this process.     

A Family-Based Analysis of the Association of the Dopamine D2 Receptor (DRD2) with Alcoholism

The possible association of the DRD2 locus, and in particular the 7aql-A1 allele, with alcoholism remains controversial, in part because of differences in allele frequencies among populations. To avoid problems associated with differences in allele frequencies in different populations, we tested whether the DRD2 locus is associated with alcohol dependence in a large family-based sample. Neither the transmission/disequilibrium test nor the Affected Family-Based Controls test provide any evidence of linkage or association between the DRD2 locus and alcohol dependence.     

Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia

We conducted a phase 1/2 study of the combination of 5-aza-2'-deoxycytidine (decitabine) and the histone deacetylase inhibitor valproic acid (VPA) in patients with advanced leukemia, including older untreated patients. A group of 54 patients were treated with a fixed dose of decitabine (15 mg/m(2) by IV daily for 10 days) administered concomitantly with escalating doses of VPA orally for 10 days. A 50 mg/kg daily dose of VPA was found to be safe. Twelve (22%) patients had objective response, including 10 (19%) complete remissions (CRs), and 2 (3%) CRs with incomplete platelet recovery (CRp). Among 10 elderly patients with acute myelogenous leukemia or myelodysplastic syndrome, 5 (50%) had a response (4CRs, 1CRp's). Induction mortality was observed in 1 (2%) patient. Major cytogenetic response was documented in 6 of 8 responders. Remission duration was 7.2 months (range, 1.3-12.6+ months). Overall survival was 15.3 months (range, 4.6-20.2+ months) in responders. Transient DNA hypomethylation and global histone H3 and H4 acetylation were induced, and were associated with p15 reactivation. Patients with lower pretreatment levels of p15 methylation had a significantly higher response rate. In summary, this combination of epigenetic therapy in leukemia was safe and active, and was associated with transient reversal of aberrant epigenetic marks.     

老年2型糖尿病血栓调节蛋白检测的临床意义

目的研究老年2型糖尿病患者慢性血管并发症的形成与血栓调节蛋白(TM)的关系。方法采用双抗体夹心酶联免疫吸附法检测128例老年2型糖尿病患者和40例正常对照者血栓调节蛋白(TM)水平。结果糖尿病组血浆TM水平显著高于正常对照组,差异有显著性(P<0.05);胃血管病变组(A组)的血浆TM显著高于无血管病变组(B组),差异有显著性(P<0.05)。结论TM水平反映了血管内皮细胞受损伤程度,血浆TM水平仅在糖尿病出现并发症时升高,因而认为TM可作为判断糖尿病患者出现血管并发症的指标。