Effect of metformin and insulin combination on monocyte chemoattractant protein-1 and cathepsin-D in type 2 diabetes mellitus

Background and aimsMonocyte chemoattractant protein-1 (MCP-1) and cathepsin-D are progressively raised in type 2 diabetes mellitus (T2DM) with both non proliferative and proliferative retinal disease. This study aimed to evaluate the effect of antidiabetic medications on MCP-1 and cathepsin-D.Methods60 patients of T2DM without retinopathy and 60 of diabetic retinopathy were enrolled to receive metformin (500 mg–1000 mg) combined with either glimepiride (1 mg–2 mg) or insulin. The effect of antidiabetic medications on serum MCP-1 and cathepsin-D was assessed.ResultsMean MCP-1 (pg/ml) and cathepsin-D (ng/ml) levels were significantly lower in patients of T2DM with and without retinopathy treated with metformin + insulin (468.52 ± 272.84 vs 234.30 ± 180.58; p < 0.01 and 460.15 ± 128.52 vs 517.33 ± 213.49; p = 0.214) as compared to patients treated with metformin + glimepiride (1434.02 ± 105.27 vs 1256.27 ± 76.76; p < 0.01 and 1689.36 ± 752.57 vs 919.69 ± 675.05; p = < 0.01). No significant correlation of MCP-1 and cathepsin-D with HbA1c, fasting and post prandial blood glucose were found.ConclusionPatients treated with metformin and insulin combination had lower serum MCP-1 and cathepsin-D levels which suggests that this combination may be more effective in reducing the progression of diabetic retinopathy. (CTRI/2018/05/013601).     

The -2518A/G polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and diabetes risk: a meta-analysis

We conducted a meta-analysis to investigate the association between the −2518A/G polymorphism in the MCP-1 gene and the risk of diabetes. Ten case-control studies were included in this meta-analysis. Results indicated this polymorphism may be a risk factor for diabetes in Caucasians. Future studies are needed to validate our conclusions.     

MCP-1与胰岛素抵抗和2型糖尿病的关系

近年来炎症学说在胰岛素抵抗及2型糖尿病发病机制中的作用备受关注。越来越多的研究提示,胰岛素抵抗和2型糖尿病是一个慢性非特异性炎症过程。单核细胞趋化蛋白-1作为炎症趋化因子CC亚族的一员,在趋化单核细胞和T淋巴细胞,诱导单核细胞、内皮细胞表达黏附分子,使各种炎性细胞尤其是单核/巨噬细胞向病变部位聚集的过程中发挥了决定性作用。而这种免疫和炎症过程有可能导致胰岛素抵抗和2型糖尿病的发生和发展。     

胰岛素强化治疗对2型糖尿病患者尿单核细胞趋化蛋白1排泄的影响

目的探讨胰岛素强化治疗对T2DM患者尿单核细胞趋化蛋白1（UMCP-1）排泄的影响及其意义。方法30例T2DM患者进行为期2周的胰岛素强化治疗,比较治疗前后DM相关代谢指标及UMCP-1排泄的变化。结果T2DM患者的FPG、2hPG、HbA1c和uMcP_1／尿肌酐（UCr）比值明显高于正常对照组;T2DM患者强化治疗后UMCP-1／ucr比值明显降低（P〈0．01）;DM患者UMCP-1／ucr比值与尿白蛋白／UCr呈正相关（P均〈0．01）。结论短期胰岛素强化治疗可降低DM患者UMCP-1排泄,减轻糖尿病高血糖状态下肾组织局部增强的炎症反应。     

血清单核细胞趋化蛋白-1水平与新诊断2型糖尿病和糖耐量减低的相关性研究

目的 探讨血清单核细胞趋化蛋白-1 （MCP-1）水平与T2DM、IGT及其危险因素的相关性.方法 检测新诊断T2DM患者32例、IGT患者46例和健康（NC）者111名血清MCP-1水平及其他生化指标,分析血清MCP-1与T2DM、IGT及其危险因素的相关性.结果 T2DM、IGT组血清MCP-1水平高于NC组（P＜0.01）.MCP-1与WHR、TC、胰岛素抵抗指数（HOMA-IR）呈正相关,与年龄、BMI、血压、FPG、2hPG和HbA1c无相关性.结论 血浆MCP-1水平与T2DM、IGT均有相关性,与WHR、TC和HOMA-IR均独立相关.MCP-1可能对T2DM和IGT发病有影响.     

PAI-1基因多态性与2型糖尿病的相关性

目的分析2型糖尿病患者（T2DM）纤溶酶原激活物抑制物（PAI）-1基因型及分布频率,探讨PAI-1基因多态性与T2DM的关系。方法观察组为34例T2DM患者,对照组为39例健康体检正常者,采用等位基因特异性引物PCR扩增技术检测各组人群PAI-1基因多态性,两组人群血浆PAI-1含量检测采用美国USCNLIFE原装人PAI-1 ELISA试剂盒,酶标仪450nm波长下测定吸光度（OD值）,两次平行测定取均值计算样品PAI．1水平。结果观察组与对照组相比PAI-1基因型频率及等位基因频率均有显著性差异（r=24．127,P〈0．001;X^2=7．312,P〈0．05）。观察组4G等位基因频率明显高于对照组,有显著性差异（X^2=6．280,P〈0．05）。观察组血浆PAI-1水平明显高于对照组（t=10．7,P〈0．01）,观察组内比较4G／4G者血浆PAI-1含量明显高于4G／5G和5G／5G者,有显著性差异（F=21．02,P〈0．001）。结论PAI-1基因多态性与T2DM间存在一定的关联性,其中4C等位基因可能是T2DM发病的危险因子。     

Study on the association between the polymorphism of MCP-1 rs1024611 and the genetic susceptibility of type 2 diabetes with sepsis

Monocyte chemoattractant protein-1 (MCP-1) rs1024611 (-2518 A > G) polymorphism are associated with inflammatory diseases. In this study, we investigate the relationship between MCP-1 rs1024611 polymorphism and genetic susceptibility of type 2 diabetes mellitus (T2DM) with sepsis.Two hundred eighty-five patients with T2DM are divided into the diabetes with sepsis group (combined group, 113 cases) and the diabetes group (172 cases). Blood samples and corresponding clinical data were collected. MCP-1 rs1024611 polymorphism in blood samples was detected by pyrosequencing. Meanwhile, the expressions of MCP-1, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 in blood samples were detected by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The relationship between different genotypes of MCP-1 rs1024611 polymorphic locus and T2DM with sepsis was analyzed by combining with the clinical data of the patients.The frequencies of rs1024611 AG/GG genotypes and G allele in T2DM with sepsis group were significantly higher than those in T2DM patients without sepsis (P = .004 for AG/GG vs AA genotypes; P = .037 for G allele vs A allele). Subgroup analysis showed that the rs1024611 G allele frequency in the septic shock group was significantly higher than the general sepsis group (P = .02). The expressions of MCP-1 and TNF-α in GG genotypes in T2DM with sepsis group were significantly higher than AA or GA genotypes (P < .05).This study preliminarily showed that the rs1024611 A > G polymorphism within the promoter region of MCP-1 gene can upregulate the expression of MCP-1 gene and proinflammatory cytokine TNF-α, which ultimately contributed to the predisposition and progression of T2DM with sepsis.     

MCP-1基因多态性与老年2型糖尿病患者并发肾功能衰竭的相关性研究

目的 探讨单核细胞趋化蛋白-1(MCP-1)基因-2518A/G多态性与老年2型糖尿病患者并发肾功能衰竭之间的相关性.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测56例2型糖尿病伴肾功能衰竭患者及56例2型糖尿病(无肾损伤)患者、50名健康对照者的MCP-1基因-2518位点的基因型分布及基...     

脂联素基因多态性与2型糖尿病的相关性研究

目的探讨脂联素基因（apM1）2号外显子＋45位点T/G多态性与滨州地区汉族人群2型糖尿病（T2DM）的关系。方法采用聚合酶链反应—限制性片段长度多态性方法 ,检测100例T2DM患者及100例健康者的apM1 2号外显子＋45位点T/G多态性。结果与健康者比较,T2DM患者G/G基因型分布、G等位基因频率明显升高,T等位基因频率明显降低（P均〈0.01）。结论 apM1可能是滨州地区汉族人群T2DM的易感基因。     

Monocyte chemoattractant protein-1 (MCP-1) 2518G/A gene polymorphism in Turkish type 2 diabetes patients with nephropathy

Tissue macrophage accumulation is thought to induce insulin resistance during obesity and stimulate the progression of diabetic nephropathy (DN). The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene polymorphism in the healthy and patients with and without DN. The MCP-1 genotypes were determined in 43 patients with nephropathy and 43 without nephropathy and a control group of 105 healthy individuals. The genotype MCP-1 (-2518G/A) distribution did differ between the control group and the type 2 diabetic patients (P?=?0.004). The frequency of the polymorphic G allele was also no similar for the group with type 2 diabetes as for the control group with 20.9 and 32.4%, respectively (P?=?0.012). The AA genotype and A allele at MCP-1 -2518 was an independent risk factor for the progression of type 2 diabetes. In conclusion, MCP-1 AA genotype and A allele may play a specific role(s) in determining diabetic susceptibility, but do not seem to be important in the clinical manifestations of DN.     

Association of the MCP-1 gene polymorphism A-2518G with carpal-tunnel syndrome in hemodialysis patients

Abstract

Carpal-tunnel syndrome (CTS) in long-term hemodialysis patients is caused by the deposition of amyloid as well as by the local inflammatory process. The recruitment of monocytes/macrophages in the tenosynovium, promoted by chemokines such as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1a (M1P-I α), is thought to play an important role in CTS development. The genetic polymorphism of these chemokines has been identified and their clinical function has been partly revealed. We attempted to analyze the relationship between these polymorphisms and their susceptibility to CTS. The subjects of this study were 366 patients who underwent hemodialysis. Ninety-five patients received surgery for CTS. No significant difference was observed in the genotype distributions of MCP-1 or MIP-lα between patients who received CTS surgery and those that did not. However, with the use of a logistic regression model, the MCP-1 GG genotype was identified as a risk factor for the development of CTS, in addition to the duration and the age of initiation of dialysis, as confirmed by a Cox proportional hazards model. In conclusion, homozygosity for G at -2518 in the MCP-1 gene might be a candidate for the genetic marker of CTS development in Japanese hemodialysis patients.     

Homocysteine levels are not associated with cardiovascular autonomic function in elderly Caucasian subjects without or with type 2 diabetes mellitus: the Hoorn Study

OBJECTIVE: Homocysteine and cardiovascular autonomic function are both predictors of cardiovascular disease and death, particularly in patients with diabetes. The mechanism by which homocysteine causes disease is unknown. The objective of our study was to determine whether hyperhomocysteinaemia is associated with impaired cardiovascular autonomic function in an age-, sex-, and glucose tolerance-stratified sample of an elderly Caucasian population. METHODS: We studied 609 subjects, 252 with normal glucose metabolism, 173 with impaired glucose metabolism, and 184 with type 2 diabetes. Cardiac cycle duration (RR interval) and continuous finger arterial pressure were measured under three conditions: during (i) spontaneous breathing, (ii) six deep breaths over 1 min, and (iii) an active change in position from lying to standing. From these readings, 10 parameters of autonomic function were assessed (three Ewing tests, six heart rate variability tests and one test of baroreflex sensitivity). These 10 measurements were summarized in a single cardiovascular autonomic dysfunction score (CADS). RESULTS: Comparing values of autonomic function measures in the lowest versus the highest quartile of homocysteine revealed no significant association between homocysteine level and autonomic function in the whole study group, nor in the individual glucose tolerance groups. Multiple adjustment for age, sex, waist-to-hip ratio, serum creatinine, use of antihypertensives and fasting insulin, confirmed this result. We found no evidence of effect modification of glucose tolerance status on the association between homocysteine and autonomic dysfunction (P for interaction for CADS = 0.79). CONCLUSIONS: There is no evidence for an association between homocysteine levels and cardiovascular autonomic function in either diabetic or nondiabetic subjects. Cardiovascular autonomic dysfunction does not help explain why hyperhomocysteinaemia is related to cardiovascular mortality.     

单核细胞趋化蛋白-1基因多态性与冠状动脉介入治疗后再狭窄的相关性研究

目的 探讨单核细胞趋化蛋白-1(MCP-1)启动子区-2518A/G基因多态性与冠状动脉(冠脉)粥样硬化病变进程及经皮冠脉腔内成形术(PCI)后再狭窄的相关性.方法 对276例接受PCI并进行冠脉造影随访的患者,采用PCR-RFLP方法进行MCP-1 -2518A/G多态性检测;按冠脉造影结果分为再狭窄组(113例)和无再狭窄组(163例),判定冠脉血管病变及再狭窄与MCP-1 -2518A/G多态性的相关性.结果 MCP-1 -2518A/G基因型频率为:AA纯合子21.0%,GG纯合子34.1%,AG杂合子44.9%,3种基因型血管病变支数和血管平均狭窄程度,差异均无统计学意义(P＞0.05).再狭窄组中AA、AG和GG基因型频率分别为23.9%、40.7%和35.4%,无再狭窄组分别为19.0%、47.9%和33.1%,差异无统计学意义(P=0.446).再狭窄组中-2518A和G等位基因频率分别为44.2%和55.8%,无再狭窄组分别为42.9%和57.1%,差异无统计学意义(P=0.761).结论 冠脉粥样硬化进程及PCI术后再狭窄可能与MCP-1 -2518A/G基因多态性无相关性.     

PGC-1α基因多态性与2型糖尿病的相关性

目的 了解华南汉族人群PGC-1αt基因单核苷酸多态性与2型糖尿病的相关性.方法 采集350例2型糖尿病患者和其父母以及366名正常糖耐量志愿者的血样,提取基因组DNA.应用PCR.限制性片段长度多态性(RFLP)和DNA直接测序技术鉴定PGC-1α基因多态性位点的基因型.应用病例.对照方法和基于家庭的单倍型相对危险度分析(HRR)和传递不平衡检验(TDT)方法分析相关多态性及其单倍型与2型精尿病的相关性.结果 (1)病例-对照研究显示Gly482Ser(G/A)多态性G、A等位基因在2型糖尿病组和正常糖耐量组分布频率分别为0.589、0.411和0.687、0.313(x2=15.076,P<0.01).Thr394Thr(G/A)、Thr528Thr(A/G)和Thr612Met(C/T)等位基因在两组间分布频率差异无统计学意义(均P>0.05).394A-482A-528A单倍型在两组间分布差异有统计学意义(x2=40.2,P<0.05),且与2型糖尿病存在连锁不平衡(t=2.503,P<0.05).(2)基于家庭研究显示PGC-1α基因Gly482Ser变异的A等位基因由父母更多地向患者传递(x2=7.217,P=0.007,HRR=1.450),TDT-ETDT结果均显示482位点A等位基因由杂合子父母传递给患病子代的频率偏离0.5(均P<0.05),单倍型TDT分析显示394A-482A-528A.612C,394A-482A-528A-612T,394A-482A-528G-612C和394A-482A-528G-612T单倍型分布频率显著偏离0.5(P<0.05或P<0.01).结论 Gly482Ser(G/A)变异与华南汉族2型糖尿病的易感性密切相关,Thr394Thr(G/A)变异可能辅助了这种作用.     

Apolipoprotein (a) levels in type 1 and type 2 diabetes mellitus

Type 1 and type 2 diabetes mellitus are both characterized by increased cardiovascular mortality and morbidity. Since several reports have indicated that apolipoprotein (a) [apo (a)] levels are positively associated with an increased risk of macrovascular disease, we investigated whether apo (a) levels are elevated in both types of diabetes mellitus and may thus represent an independent risk factor for atherosclerotic disease. Apo(a) concentrations in type 1 diabetic patients were not significantly different from matched controls (276±78 vs 149±46 units/l). Type 2 diabetic patients had considerably higher levels of apo (a) than matched controls (471±89 vs 221±61 units/l,P=0.06), though the difference was not statistically significant. However, concentrations of apo (a) were above 300 units/l in 36% of type 1 and 67% of type 2 diabetic patients, but in only 14% and 25% respectively of matched control subjects. Plasma triglycerides were positively and independently correlated with apo (a) levels in both diabetic and non-diabetic subjects. On the other hand, no significant correlation was found between apo (a) levels and glycosylated haemoglobin, total cholesterol or high density lipoprotein cholesterol in any of the groups studied. In conclusion, apo (a) levels are not significantly elevated either in type 1 or type 2 diabetic patients without proteinuria and in moderate metabolic control; however, levels above 300 units/l were 2.6 times more frequent in both types of diabetes mellitus than in carefully age-, sex-, and weight-matched control subjects.     

抵抗素基因+299G/A多态性与T2DM并高血压病的相关性

目的研究抵抗素基因＋299G／A多态性与中国北方地区汉族人群2型糖尿病（T2DM）并高血压病的关系。方法采用聚合酶链式反应-限制性片段长度多态性技术检测北方地区汉族人群261例T2DM患者的抵抗素基因内含子2区299G／A突变。结果T2DM组GG、GA、AA基因型及G／A等位基因频率与非T2DM组比较有显著统计学差异（P〈0．01）；T2DM组GG基因型携带者空腹血糖明显高于AA基因型携带者（P〈0．05）。多元线性逐步回归分析显示，抵抗素基因＋299G／A与收缩压、舒张压无明显相关性。结论抵抗素基因＋299G／A多态性与T2DM有关．与高血压病元明显相关性。     

1型糖尿病并发慢性胆囊炎患者外周血IL-6基因多态性研究

目的 分析外周血IL-6 174C/G基因型和等位基因频率在研究人群中的分布情况,以探讨1型糖尿病（T1DM）并发慢性胆囊炎患者外周血IL-6基因多态性的变化。方法 收集1型糖尿病并发慢性胆囊炎患者110例和健康对照者120例。采用聚合酶链反应-限制性片段长度多态性法对所有受检者进行外周血基因多态性检测,计算基因型频率和等位基因频率,并结合问卷调查和临床生化检查的相关信息进行病例对照分析研究。应用SPSS 17.0统计软件包行统计分析。结果 纳入本研究的两组人群性别和年龄具有可比性,1型糖尿病并发慢性胆囊炎患者体质指数（BMI）为（28.15±3.98） kg/m2,显著高于健康人的（26.86±6.52） kg/m2（P＜0.05）;在110例1型糖尿病并发慢性胆囊炎患者中,伴有高血压现患例数65例（59.09%）,显著高于健康人的32.50%（39/120,P＜0.01）; 1型糖尿病并发慢性胆囊炎患者存在糖尿病家族史的比例显著高于健康人（54.55%对10.83%,P＜0.01）; 1型糖尿病并发慢性胆囊炎患者吸烟（13.64%）和饮酒（19.09%）史的比例显著高于健康人（分别为11.67%和8.33%,P＜0.01）;1型糖尿病并发慢性胆囊炎患者外周血IL-6 174C/G基因CC基因型为40.91%,显著高于健康人的28.33%（P＜0.05）,而GG基因型为7.27%,显著低于健康人的19.17%（P＜0.05）,C等位基因分布为52.73%,显著高于健康人的15.00%（P＜0.01）;单因素分析结果提示,携带IL-6 174 C等位基因【（OR=1.357(1.037～1.776),P＜0.05】、存在高血压现病【OR=1.324（1.187～1.476）,P＜0.01】、肥胖【OR=1.165（1.087～1.249）和有饮酒史【OR=1.113（1.046～1.184）,P＜0.01】为T1DM患者并发胆囊炎的危险因素;多因素Logistic回归分析结果提示携带IL-6 174 C等位基因【OR值及其95%可信区间分别为1.258（1.119～1.413）】、高血压【1.225（1.032～1.454）】和肥胖【1.167（1.056～1.289）,P＜0.01】以及饮酒史【OR值为1.111（1.006～1.228）,P＜0.05】为T1DM患者并发胆囊炎的独立危险因素。结论 IL-6 -174C/G基因多态性与1型糖尿病患者并发胆囊炎的易感性有相关关系。