糖尿病视网膜病变与血清Ⅳ型胶原和层粘连蛋白以及粘附分子变化的相关性

目的 探讨糖尿病视网膜病变不同时期细胞外间质、血管基膜成分以及血管内皮细胞粘附分子在血循环中的变化，了解他们与血管基膜和血管内皮细胞损伤的相关性。方法 85例(男40例、女45例)2型糖尿病患者分无视网膜病变(NDR)组31例、背景期视网膜病变(BDR)组24例和增殖期视网膜病变(PDR)组30例，采用放射免疫法和ELISA法测其血清Ⅳ型胶原(ⅣC)、层粘蛋白(LN)和血管内皮细胞粘附分子(sVCAM—1)含量，同时设健康体检者20人为对照组。结果 三组糖尿病患者血清LN、ⅣC、sVCAM—1水平均高于对照组。PDR组的血清LN、ⅣC和sVCAM—1水平与对照组比较，差异有非常显著意义(P＜0．01)，与NDR组比较，差异也有非常显著意义(P＜0．01)；BDR组血清LN、ⅣC和sVCAM—1水平与对照组比较，差异有非常显著意义(P＜0．01)；BDR组血清LN、ⅣC和sVCAM—1水平与对照组比较，差异有非常显著意义(P＜0．01)；PDR组与BDR组比较，仅LN、ⅣC差异有非常显著意义(P＜0．01)；BDR组与NDR组比较，仅sVCAM—1差异有显著意义(P＜0．05)。三组糖尿病患者血清三项指标之间无相关性(分别为r＝0．119，r＝0．167和r＝-0．210；P＞0．05)。结论 血清ⅣC、LN和sVCAM—1用于联合检测，能较好地反映糖尿病微血管病变的发展过程，为其早期诊断和治疗提供依据，也可作为糖尿病视网膜病变严重程度的估计和预后判断的指标。     

2型糖尿病患者非糖尿病一级亲属血清高敏C反应蛋白与胰岛素抵抗的相关性

目的探讨血清高敏C反应蛋白（hsC-RP）在2型糖尿病（T2DM）发病中的作用。方法利用ELISA方法检测72例T2DM患者非糖尿病一级亲属（FDR）和68例健康对照者（NC）血清hsC-RP、Fins、FPG等，并用HOMA—IR公式计算胰岛素抵抗指数。结果（1）FDR组血清hsC—RP水平较NC组升高（P〈0.01），HOMA—IR高于NC组（P〈0.01）；（2）血清hsC-RP水平与HOMA-IR（r=0．307，P〈0．01）、Fins（r=0．286，P〈0．05）、BMI（r=0．250，P〈0．05）、LDL—C（r=0．302，P〈0．05）、TC（r=0．267，P〈0．05）相关。结论慢性炎症与胰岛素抵抗密切相关，hsC-RP升高是2型糖尿病发生的一个预测因子。     

对氧磷脂酶-1和氧化低密度脂蛋白在2型糖尿病肾病中的作用

目的 探讨2型糖尿病（DM0对氧磷脂酶－1（PON－1）和氧化低密度脂蛋白（ox-LDL)与内皮细胞和血小板功能的关系,以及对糖尿病肾病（DN）发生、发展的影响。方法 用酚乙酸酯为底物的速率法测定91例2型DM患者血清PON－1,用ELISA法测定ox-LDL,同时测定血清一氧化氮（NO）、血管性假血友病因子（VWF）及血浆颗粒膜蛋白（GMP140）,并与正常人作对照,以24h尿白蛋白排泄率（UAER）将DM患者分成三组。结果 血清PON－1活性在2型DM三组中与对照组比较显著降低（P＜0．01）,血浆ox-LDL浓度则显著升高（P＜0．01）,二者在DM三组之间的差别有显著性（P＜0．05）。PON－1与尿白蛋白呈显著性负相关（P＜0．01）,ox-LDL则与之呈显著性正相关（P＜0．01）,二者之间呈负相关（P＜0．01）。PON－1与血NO呈正相关,与GMP 140呈显著负相关;ox-LDL与血NO呈负相关,与VWF、GMP140呈正相关,经Logistic回归分析,提示ox-LDL是DN的危险因子。结论 DM的高血糖和脂代谢紊乱造成的PON－1酶活性下降以及脂质过氧化物的堆积,使内皮细胞的完整性及功能受损,同时血小板的活化程度明显增强。它们的共同作用与DN的发生、发展密切相关。     

2型糖尿病相关因素与sICAM-1关系的探讨

为探讨2型糖尿病(DM)患者可溶性细胞间粘附分子(sICAM—1)水平变化及其与血糖代谢控制、胰岛素抵抗(IR)、血压(BP)、体重指数(BMI)的关系，采用酶联免疫吸附法测定51例2型DM患者及20例查体健康者的血清sICAM—1水平，同时检测其空腹胰岛素(FIN)、糖化血红蛋白(GHbAlc)、空腹血糖(FPG)、Bp、BMI。结果显示，2型DM患者血清sICAM—1显著高于正常对照组(P＜0．01)，且血清sICAM—1与BMI、GHbAlc及收缩压呈正相关，相关系数r分别为0．441、0．435、0．311，P＜0．01、0．01、0．05。提示2型DM血清sICAM—1水平升高可能由肥胖和高血糖引起，控制血糖、减轻体重有助于降低sICAM—1。     

糖尿病合并冠心病患者F1+2及SFMC的变化及意义

为探讨F1 2及SFMC在糖尿病合并冠心病中的变化及意义，采用酶联免疫吸附法(ELISA)检测28例糖尿病合并冠心病患者(试验组)静脉血凝血酶原片段1 2(F1 2)及纤维蛋白单体复合物(SFMC)水平，并与25例单纯糖尿病患者(对照组)进行比较。结果显示，试验组F1 2、SFMC水平均明显高于对照组(P＜0．005、＜0．01)，其它出凝血指标如凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fbg)、血浆因子Ⅶ促凝活性(FⅦ：c)等两组比较无明显差异(P＞0．05)。试验组与对照组空脂血糖(FBG)、甘油三酯（TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL—C)水平无明显差异(P＞0，05)；低密度脂蛋白胆固醇(LDL—C)水平有显著性差异(P＜0．05)。两组血流变学中全血比粘度(中切)、血浆比粘度无显著性差异(P＞0．05)，红细胞压积、红细胞聚集指数有显著性差异(P＜0.05)。提示血栓前状态与糖尿病合并冠心病有密切关系，F1 2及SFMC可以作为糖尿病患者发生冠心病的预测指标。     

糖尿病对骨密度及相关激素的影响

目的 观察DM患者骨密度（bone mineral density,BMD)及其相关激素的改变，并探讨其发生机制。方法 采用双能（线吸收法测量2型DM患者68例、1型DM患者54例和健康人62例的BMD，放免法测定血清骨钙素、降钙素和25羟维生素D3，免疫放射法测定血清完整甲状旁腺素及I型胶原羧基末段前肽。结果 ①两组DM患者全血HbA1c水平均显著高于对照组（P＜0．01），血清骨钙素水平显著低于对照组（P＜0．01）；②2型DM组BMI、大转子BMD显著高于对照组和1型DM组（BMI，P＜0．01；BMD，P＜0．05）；1型DM组股骨颈BMD低于对照组和2型DM组（P＜0．05），经BMI纠正后，1型DM组股骨颈BMD仍低于对照组（P＜0．05）；③1型DM组各位点BMD与血清I型胶原羧基末段前肽水平呈负相关（P＜0．05），2型DM组腰椎和大转子BMD与全血HbA1c水平呈负相关（P＜0．05）。结论 与健康人群相比，1型DM患者BMD明显降低，2型DM患者BMD明显增高，但经BMI纠正后，这种差异性消失；骨转化降低以及糖尿病代谢紊乱可能参与了糖尿病骨质疏松的发生。     

中心型肥胖与胰岛素抵抗、2型糖尿病相关性探讨

3800名人群中，中心型肥胖342人为A组，外周型肥胖228人为B组。3230名非肥胖为C组即对照组。比较RISI，A组明显低于B组和C组，P＜0．01；B组亦低于C组，P＜0．05。各组间IR、IGT、DM发病率比较，A组、B组IR、IGT、DM发生率比C组明显增高，P＜0．05；A组比B组IR、DM发病率亦明显增高，P＜0．005；A组比B组IR、DM发病率亦明显增高，P＜0．005；而IGT发生率虽比B组增高，但无统计学意义，P＞0．05。结论 中心型肥胖胰岛素抵抗、糖尿病发病率明显高于外周型肥胖和非肥胖。     

2型糖尿病患者血清β-淀粉样蛋白水平及其与胰岛素抵抗关系的研究

为探讨2型糖尿病（DM）患者β－淀粉样蛋白（β－AP）水平及其与胰岛素抵抗（IR）的关系，了解2型DM与老年性痴呆（AD）的内在联系，将63例无认知障碍及脑血管病的2型DM患者按病程分为DM1组（22例，病程≥5年）和DM2组（41例，病程＜5年），并与29例健康者作对照，分别测定β－AP，空腹血糖（FPG），空腹胰岛素（FINS），糖化血红蛋白（HbA1C），总胆固醇（TC）及甘油三酯（TG），计算胰岛素敏感指数（ISI）。结果显示，DM组β－AP明显高于对照组；DM1组和DM2组的各项指标均无明显差异；DM组β－AP与FPG，FINS，HbA1C呈正相关（P分别＜0．025，＜0．025和＜0．05），与ISI呈显著负相关（P＜0．01），与DM病程，TC，TG无明显相关性（P均＞0．05）。认为2型DM患者存在β－AP表达增加，IR可能起促发作用，2型DM与AD可能有一个共同的病理机制，IR参与了此机制。     

新诊2型糖尿病患者血清 SPARC 水平及其与胰岛素抵抗的关系

目的：观察新诊断2型糖尿病（T2DM）患者血清富含半胱氨酸酸性分泌蛋白（SPARC）水平变化,探讨其与胰岛素抵抗的相关性。方法检测新诊断未治疗的60例T2DM患者（ T2DM组）及50例同期健康体检者（对照组）的血清SPARC、空腹血糖（ FBG）、糖化血红蛋白（ HbA1C ）、空腹胰岛素（ FINS）、血脂及BMI、腰围、臀围、腰臀比（WHR）,计算胰岛素抵抗指数（HOMA-IR）、胰岛β细胞功能指数（HOMA-β）。结果 T2DM组血清SPARC为（19．26±2．07）μg/L ,对照组为（14．75±1．66）μg/L,P＜0．01。线性相关分析,SPARC水平与TG、FBG、HbA1C、HOMA-IR呈明显正相关（r分别为0．35、0．32、0．41、0．38,P均＜0．01）,与HOMA-β、HDL-C呈负相关（r分别为－0．48、－0．34,P均＜0．01）。多因素线性回归分析显示,HbA1C、FBG、HOMA-IR均为血清SPARC的决定因素（回归系数分别为0．624、0．625、0．709,P均＜0．05）。结论新诊断T2DM患者血清SPARC水平升高,且血清SPARC水平与胰岛素抵抗有关。     

血清IGF—1、IGFBP—1，GH水平与糖尿病慢性并发症关系的研究

目的：揭示胰岛素样生长因子－1,胰岛素样生长因子结合蛋白－1,生长激素对糖尿病慢性并发症的发生,发展的影响。方法：测定20例健康对照者和62例2例糖尿病,10例1例糖尿病患者的胰岛素样生长因子－1（IGF－1）,胰岛素样生长因子结合蛋白－1（IGFBP－1）,生长激素（GH）及血浆胰岛素（INS）,C肽（C－P）,糖化血红蛋白（HbAlc)指标,结果：（1）IGF－1水平,1型糖尿病患者显著低于对照组（P＜0．05）,2型糖尿病患者显著低于对照组（P＜0．05）,（2）IGFBP－1水平,1型糖尿病患者显著高于对照组（P＜0．05）,2型糖尿病肥胖型伴高胰岛素血症者显著低于对照组（P＜0．05）;（3）GH水平,1型糖尿病患者显著高于对照组（P＜0．05）,2型糖尿病与对照组无显著差异（P＞0．05）,（4）合并糖尿病肾病及视网膜病变患者IGF－1水平均较对照组增高（P＜0．05）,（5）IGF－1水平与HbAlc间呈负相关（P＜0．01 2型r=-0.62 1型r=-0.73)。结 论：IGF－1,IGFBP－1,GH水平的检测对糖尿病慢性并发症,特别是微血管病变的发生,发展有重要的临床意义。     

冠心病及2型糖尿病合并冠心病与对氧磷酯酶192Gln/Arg基因多态性的相关性研究

为探讨冠心病(CHD)及2型塘尿病(DM)合并CHD与对氧磷酯酶(PON1)192G1n／Arg基因多态性的关系，采用多聚酶链反应—限制性片段长度多态性(PCR—RFLP)法检测了104例查体健康者(对照组)和76例CHD、96例2型DM合并CHD患者的PONl—192位点的多态基因型；同时测量其体重指数(BMI)，检测总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL—C)、低密度脂蛋白胆固醇(LDL—C)、载脂蛋白A I(ApoA I)、载脂蛋白B(Apo B)。结果显示，PONl—192位点QQ、QR、RR基因型及Q、R等位基因频率在2型DM合并CHD组与对照组比较均有显著性差异(P＜0．05、＜0．01)；但CHD组与对照组比较无显著性差异(P＞0．05)。中国人与白种人PON1-192位点基因型及等位基因频率比较有显著性差异(P＜0．01)。含R等位基因的基因型QR、RR是2型DM合并CHD的独立危险因素。提示PONl—192G1n／Arg基因多态性与2型DM合并CHD有相关性，与CHD无相关性。     

老年2型糖尿病合并非酒精性脂肪肝患者血清蛋白激酶Cε活性和胰岛素抵抗的关系研究

目的探讨老年2型糖尿病(T2DM)合并非酒精性脂肪肝(NAFLD)患者血清蛋白激酶Cε(PKCε)活性与胰岛素抵抗的相关性。方法回顾性分析2017年10月至2018年10月西安交通大学医学院第二附属医院住院的T2DM患者229例,根据病情分为T2DM组112例,T2DM+NAFLD组117例,另选同期健康对照组110例。比较3组入选者临床资料和实验室检查结果,计算稳态模型的胰岛素抵抗指数(HOMA-IR),采用酶联免疫吸附法测定血清PKCε活性,并分析其与胰岛素抵抗的相关性。结果T2DM+NAFLD组患者血清PKCε活性和HOMA-IR均高于单纯T2DM组和健康对照组[(195.5±62.1)μg/L比(188.7±61.2)μg/L和(89.1±20.2)μg/L、(12.5±7.9比14.1±5.7和5.8±4.1),F值分别为9.76、10.21,均P=0.010]。Pearson相关分析,T2DM+NAFLD组患者血清PKCε活性、HOMA-IR及三酰甘油呈正相关(r值分别为0.339、0.305、0.329,均P<0.015)。Logistic回归分析,血清PKCε活性、HOMA-IR和三酰甘油是T2DM+NAFLD组的危险因素(β值分别为0.849、0.022和0.710,均P<0.05)。血清PKCε活性升高是T2DM合并NAFLD的独立影响因素。结论老年T2DM合并NAFLD患者血清PKCε活性升高与胰岛素抵抗呈正相关,降低血清PKCε活性和改善胰岛素抵抗有助于延缓或改善T2DM及NAFLD。     

Lipoprotein lipase (LPL) mass in preheparin serum reflects insulin sensitivity

Lipoprotein lipase (LPL) is one of the enzymes regulated by insulin and its plasma activity reflects insulin sensitivity. Although intravenous heparin injection is required to measure LPL activity, we can detect LPL mass in preheparin serum (Pr-LPL mass) by immunoassay. In this study, we examined whether Pr-LPL mass reflects insulin sensitivity. We measured Pr-LPL mass, insulin sensitivity (Si), and acute insulin release in response to a glucose bolus (AIRg) in subjects with normal glucose tolerance (NGT; n = 23), impaired glucose tolerance (IGT; n = 10), and Type II diabetes mellitus (DM; n = 48). Si and AIRg were determined by minimal model analysis. We also compared Pr-LPL mass with the homeostasis model assessment of insulin resistance (HOMA-R) and the urinary excretion of C-peptide (urine CPR). We found that Pr-LPL mass correlated significantly with Si ( r = 0.354, P < 0.01) in all the subjects. This correlation was still significant in the NGT group (P < 0.472, P < 0.05), DM group (r = 0.311, P < 0.01), and DM group with a fasting plasma glucose >150 mg/dl ( n = 20, r = 0.459. P < 0.05). Moreover, Pr-LPL mass correlated negatively with HOMA-R (r = -0.272. P < 0.05) and fasting IRI (r = -0.256, P < 0.05). By contrast, Pr-LPL mass was not correlated with either urine CPR or logAIRg that reflect the ability to secrete insulin. In conclusion, Pr-LPL mass reflects insulin sensitivity. We speculate that Pr-LPL mass might be used to assess insulin sensitivity not only in the general population but also in advanced diabetic patients.     

The relationship of lmp2 and DR3 genes with susceptibility to type I diabetes mellitus in south China Han population

AIM:To study the relationship of lmp2 and DR3 genes with type I diabetes mellitus.METHODS:lmp2 genotypes and DR3 were identified in 68 patients with type I diabetes mellitus (I -DM) and 71 healthy controls. Then,I -DM patients and controls were respectively allocated into DR3-positive and DR3-negative groups. The frequencies of lmp2 and DR3 gene in random subjects, and lmp2 genotypes in DR3 matched subjects were compared between I -DM patients and controls. At the same time, I DM patients were divided into 3 groups based on the onset age of diabetics:group A < = 14 years, group B 15-30 years and group C > = 31 years.RESULTS:The frequency of DR3 in I-DM patients was significantly higher than that in controls (47% vs 21%, P < 0.005), and it was significantly higher in group A than that in group B+C (70% vs 36%, X(2) = 7.07, P < 0.01). There was a significant difference among groups with different onset age of diabetics (X(2) = 8.19, rp = 0.33, P <0.05). In random subjects, the frequency of lmp2-R/R in I -DM patients was lower (43% vs 61%, P <0.05)and lmp2-R/H higher (53% vs 28%, P<0.05) than that in controls, and there was no significant difference among groups with different onset age of diabetics.In DR3-positive subjects, the frequency of lmp2-R/R in I-DM patients was lower (47% vs 87%, P<0.05) and lmp2-R/H higher (47% vs 13%, P <0.05) than that in controls. In DR3-negative subjects,the frequency of lmp2-R/H in I -DM patients was higher than that in controls (58% vs 32%, P <0.01), but the frequency of lmp2-R/R and lmp2-H/H was not significantly different between these two groups.CONCLUSION:DR3 gene may be one of the susceptible genes of I-DM,and significantly related to the onset age of diabetics, and the persons with DR3 may have an younger onset age of diabetes.The lmp2-R/R may be the protective genotype of I-DM, and lmp2-R/H the susceptible genotype. These were not affected by DR3 gene. lmp2 genotypes were not related with the onset age of diabetics.     

Insulin resistance, endocrine function and adipokines in type 2 diabetes patients at different glycaemic levels: potential impact for glucotoxicity in vivo

OBJECTIVE: To evaluate the interplay between hyperglycaemia, insulin resistance, hormones and adipokines in patients with type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: Ten patients with T2DM with good glycaemic control (G), 10 with poor control (P) and 10 nondiabetic control subjects (C) were matched for sex (M/F 6/4), age and body mass index. A hyperinsulinaemic, euglycaemic clamp was performed and cytokines and endocrine functions, including cortisol axis activity were assessed. RESULTS: Patients with diabetes were more insulin resistant than group C, and group P exhibited the highest degree of insulin resistance (P = 0.01, P vs C). Tumour necrosis factor (TNF)-alpha levels were elevated in patients with diabetes (P = 0.05) and group P had the highest levels of fasting serum cortisol (P = 0.05), nonesterified fatty acids (NEFA; P = 0.06) and C-reactive protein (CRP; P = 0.01). Adiponectin levels were lower in the P group. In partial correlation analyses, significant associations were found: glycaemic level (HbA1c) with insulin resistance, TNF-alpha, CRP and basal and ACTH-stimulated cortisol levels, insulin resistance with plasma NEFA, TNF-alpha and stimulated cortisol levels. CONCLUSION: Poor glycaemic control in patients with T2DM was associated with insulin resistance and with elevated TNF-alpha, CRP and basal as well as stimulated cortisol levels. Inflammatory mediators, e.g. TNF-alpha, may contribute to insulin resistance in hyperglycaemic patients with T2DM and this might be a partial explanation for glucotoxicity.     

Correlation between the activities of lipoprotein lipase and paraoxonase in type 2 diabetes mellitus

In type 2 diabetes mellitus the decreased catabolism of triglyceride-rich lipoproteins as a consequence of mainly the decreased lipoprotein lipase activity results in hypertriglyceridaemia and other lipoprotein alterations promoting atherosclerosis. The high-density lipoprotein-associated enzyme, paraoxonase, prevents the oxidation of low-density lipoprotein, which is an antiatherogenic effect.

Aim

to examine the relation between the activities of enzymes influencing HDL remodelling- LPL and PON- in type 2 diabetes mellitus.

Methods

56 newly diagnosed type 2 diabetic patients and 39 healthy controls were involved in the study. The serum PON activity was measured spectrophotometrically using paraoxone as substrate. PON phenotype was determined by the dual substrate method, PON mass was measured by ELISA. The determination of lipoprotein lipase activity was performed using ³H-triolein.

Results

We noticed smaller PON activity decrease in our newly diagnosed diabetic subjects compared to the previous studies which investigated the alteration of enzyme activity after a longer duration of diabetes mellitus. The lipoprotein lipase activity showed a positive correlation with PON activity (r = 0.43; P < 0.02). Interestingly, the PON activity of the homozygous-low activity group did not correlate with the LPL activity, while in the heterozygous and homozygous-high activity groups there was a significantly positive correlation (r = 0.51; P < 0.05) between PON and LPL activity.

Conclusion

Besides lipid alterations, the metabolic changes of type 2 diabetes mellitus influence the reduction of the antioxidant capacity of HDL by remodelling HDL and decreasing PON activity via modification of lipoprotein lipase activity, which might contribute to accelerated atherosclerosis.     

HLA and complement allotypes in Type 1 (insulin-dependent) diabetes

Summary A group of patients with Type 1 (insulin-dependent) diabetes mellitus was investigated for HLA-A, B and DR antigens as well as C4 and factor B polymorphism. A significant excess of DR3/DR4 heterozygotes was observed (27% versus 17% by Hardy-Weinberg expectation). The factor B allele BfF1 was present in 13% of patients with Type 1 diabetes (gene frequency of 0.08 versus 0.01 in control subjects). A rare C4 B allele, C4 B2.9, was found in 18% of patients with Type 1 diabetes (n=63) compared with 1.1% of control subjects (n=176). Total C4 deficiency at the C4A locus (C4AQ0,0) was present in 10% of patients with Type 1 diabetes compared with 0% of control subjects. Examination of HLA, C4 and Bf phenotypes in patients with Type 1 diabetes suggested that three high risk supratypes, HLA-A1 B8 BfS C4AQ0 C4 B1 DR3; HLA-B18 BfF1 C4A3 C4BQ0 DR3; HLA-A2 CW3 BW62 BfS C4A3 C4 B2.9 DR4 are markers for susceptibility alleles.     

Gln-Arg192 polymorphism of paraoxonase 1 is associated with carotid intima-media thickness in patients of type 2 diabetes mellitus of Chinese

Serum paraoxonase (PON) is a high-density lipoprotein-bound enzyme that can prevent oxidation of low-density lipoprotein by hydrolyzing lipid peroxides and thus exert an anti-atherogenic effect. Recent studies have suggested that glutamine(Q isoform)/arginine(R isoform) polymorphism at position 192 of PON(1) gene is associated with macrovascular disease of type 2 diabetes mellitus (T2DM). We re-investigated this relationship using carotid intima-media thickness (IMT) as a surrogate continuous variable for macroangiopathy. The genotype and allele frequency of PON(1) 192 Q/R polymorphism was assayed by polymerase chain reaction-restriction fragment length polymorphism in 152 type 2 diabetic patients and 128 healthy subjects from a population of Chinese Han nationality in ChengDu area. The carotid IMT was measured by B-mode ultrasonography in type 2 diabetic patients. No differences were found in PON(1) gene Q/R polymorphism in the type 2 diabetic patients when compared with the control group. The mean carotid IMT in type 2 diabetic subjects with the QQ, QR and RR genotype was 0.65+/-0.27, 0.83+/-0.27 and 1.05+/-0.32 mm, respectively. One-way ANOVA showed that IMT was significantly greater in the RR subgroup than in both QR and QQ subgroups (P<0.01). Multivariate logistic regression analysis showed R allele to be the main determinant of IMT variability (OR 4.0 95% CI 2.10-7.40 P=0.005). Our data support the view that 192 R allele of PON(1) gene is a risk factor for macrovascular disease of T2DM in Chinese.     

Modulation by blood glucose levels of activity and concentration of paraoxonase in young patients with type 1 diabetes mellitus

Paraoxonase (PON) is a high-density lipoprotein (HDL)-associated esterase, which may prevent the transformation of low-density lipoproteins (LDL) into biologically active, atherogenic particles. PON concentration and activity are affected by PON1 gene polymorphisms and found to be altered in type 2 diabetes patients with retinopathy. We investigated serum PON concentration, in vitro activity and polymorphism at position 54 (L/M, Leu-Met54) in 193 Caucasian adolescents and young adults (88 males, 105 females) with type 1 diabetes mellitus, as well as its relationship to the presence of retinopathy. An inverse linear correlation was found between blood glucose levels and both serum PON concentration (r = -.20, P =.017) and its activity (r = -0.17, P =.037). Patients with elevated blood glucose values (> or =10 mmol/L) had significantly lower levels of both PON concentration (P =.003) and activity (P =.028) than those with lower glucose levels. After adjusting for blood glucose and diabetes duration, PON activity was significantly higher in patients with different stages of retinopathy compared with those without retinopathy (P =.003). The L/L genotype was closely associated with the presence of retinopathy (P <.0001). These data show that young people with type 1 diabetes and the L/L polymorphism at position 54 of PON1 gene are more susceptible to retinal complications. However, the role of serum PON concentration and activity as a possible marker for monitoring late microvascular complications in these patients has to be established.     

心-踝血管指数与颈动脉内膜中膜厚度在动脉硬化疾病评价中的价值

目的比较心-踝血管指数与颈动脉内膜中膜厚度对不同动脉硬化疾病严重程度的判断价值。方法在849例同时行心-踝血管指数和颈动脉内膜中膜厚度测定的门诊和住院患者中,筛选出年龄55～70岁之间的351例作为最终研究对象。按临床动脉硬化疾病的有无与程度分为三个层面:A层:无动脉硬化危险因素组;B层:包括高血压、糖尿病、心绞痛和高脂血症组;C层:经造影证实存在冠状动脉狭窄和已有临床心脑动脉硬化终末事件如心肌梗死和脑梗死组。从不同层面比较心-踝血管指数和内膜中膜厚度与动脉硬化性疾病严重程度的相关性。849例中,未做年龄范围限制时,共有糖尿病患者112例,对其病程与心-踝血管指数和内膜中膜厚度的相关性作比较分析。结果除单纯高脂血症组之外,心-踝血管指数测定值在A、B、C三个不同层面能够表现出显著的差异,呈现出"阶梯效应";而内膜中膜厚度测定值相对于心-踝血管指数在三个不同层面表现出的差别明显减弱,甚至糖尿病组的测定值远远高于已有明确动脉硬化终末事件组如心肌梗死和脑梗死。在已有明确糖尿病病程的患者中,心-踝血管指数与糖尿病病程呈显著正相关(r=0.499,P<0.001),而内膜中膜厚度与病程的相关性(r=0.195,P<0.038)明显弱于心-踝血管指数。结论心-踝血管指数和内膜中膜厚度与大动脉硬化性疾病均有不同程度的相关性,而心-踝血管指数在评价整体而非局部的动脉硬化程度上相对于内膜中膜厚度具有一定的优势,其与动脉硬化的严重程度具有更大的吻合性,而内膜中膜厚度则更多地偏重于对局部动脉壁硬化的判断。