同型半胱氨酸对老年2型糖尿病患者大血管病变的影响

目的 探讨血清总同型半胱氨酸(tHcy)水平与2型糖尿病(T2DM)患者大血管病变间的关系,并分析影响T2DM患者tHcy代谢的因素. 方法 167例老年T2DM 患者分为2组:无大血管并发症组(75例)和T2DM合并大血管病变组(92例);42例正常体检老人作为正常对照组.酶联免疫吸附法测定血清tHcy浓度;自动生化分析仪测定空腹血糖(FBS)、尿素氮(BUN)、肌酐(CREA)、总胆固醇(TC)和三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、糖化血红蛋白(HbA1c);电化学发光仪测定血清胰岛素(INS).对各指标的组间差异进行统计学分析. 结果 tHcy在T2DM合并大血管病患者组血浆浓度较T2DM无大血管并发症组和对照组高,差异具有统计学意义(P＜ 0.05),血清Hcy水平仅与空腹INS水平呈正相关(r= 0.56,P＜0.01). 结论 tHcy参与了T2DM大血管病变的发病过程,tHcy水平可能与胰岛素抵抗有关.     

Plasma homocysteine is associated with nonproliferative retinopathy in patients with type 2 diabetes without renal disease

Background and aimsThis study aimed to assess the role of plasma homocysteine (Hcy) in the development of nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes (T2DM) without chronic kidney disease.MethodsThis was a cross-sectional study that included 94 T2DM. Hcy, serum 25-hydroxy (25-OH) vitamin D, vitamin B12, and folate were determined by the CMIA method. NPDR was determined according to the EURODIAB retinal photography methodology and optical coherence tomography (OCT) of the macula.ResultsCompared to patients without NPDR, patients with NPDR had longer diabetes duration (p < 0.001), higher Hcy (p < 0.001), lower vitamin B12 (p = 0.028) and lower estimated glomerular filtration rate (eGFR) (p = 0.004). NPDR was positively associated with diabetes duration (p < 0.001), HbA₁c (p = 0.049) and Hcy (p < 0.001), and negatively with vitamin B12 (p = 0.027) and eGFR (p = 0.005). Logistic regression analyses showed that diabetes duration (OR = 1.13, p < 0.001), Hcy (OR = 1.06, p = 0.047), and eGFR (OR = 0.96, p = 0.004) were the main predictors of NPDR in T2DM. Stepwise regression analyses showed that the best model for predicting Hcy (R2 = 0.104) included vitamins B12 and D.ConclusionsHigher Hcy is associated with NPDR and may play a role as a risk factor for its development in T2DM. Vitamins B12 and D seem to modify this association.     

2型糖尿病患者血浆总同型半胱氨酸水平与大血管病变的关系

目的　探讨 2型糖尿病患者 (T2 DM)血浆总同型半胱氨酸 (st Hcy)水平、影响因素及其与大血管病变的关系。　方法　对 1 91例 T2 DM患者及 2 3名正常对照人群采用高压液相层析方法测定 st Hcy、B型超声检查测定颈动脉内膜中层厚度 (IMT) ,并测定各临床、生化参数。　结果　 (1 )T2 DM患者组 st Hcy总体水平与正常对照组比较差异无显著意义 (P=0 .31 )。其中 st Hcy≥ 1 5 .1μm ol/L 组的年龄、高血压病程、血清肌酐、尿酸、尿白蛋白排泄率、IMT增厚发生率较 st Hcy<1 5 .1μm ol/L 组高 ,肾小球滤过率、糖化血红蛋白较 st Hcy<1 5 .1 μm ol/L 组低 (P<0 .0 0 1～ 0 .0 5 )。(2 ) IMT增厚组 st Hcy和高 st Hcy百分率较 IMT正常组和正常对照组明显增高 (P<0 .0 5～ 0 .0 0 1 )。多元逐步线性回归分析显示 ,st Hcy与 IMT增厚呈独立相关。 (OR=1 .36 5 ,P<0 .0 0 1 ,95 %可信区间 1 .1 39～1 .6 37)。　结论　 T2 DM患者 st Hcy受病程不同阶段的多种因素影响。st Hcy增高是大血管病变的独立危险因素     

Asymmetric dimethylarginine as a risk factor for cardiovascular disease in Japanese patients with type 2 diabetes mellitus

Aims Although asymmetric dimethylarginine (ADMA) is known to be involved in the developing process of cardiovascular diseases (CVD), little is known about the effects of ADMA on atherosclerosis in Asian patients with diabetes , who have the racial feature of lower body mass index (BMI) and decreased capacity of insulin secretion and sensitivity. Methods We employed 55 Japanese patients with type 2 diabetes mellitus (mean age, 64·2 years; 56% men) in a 6‐month‐longitudinal study and 450 patients (mean age, 62·7 years; 56% men) in a cross‐sectional study and examined the association of serum ADMA with atherosclerosis parameters [intima‐media thickness (IMT) and brachial‐ankle pulse wave velocity (baPWV)] as well as with the presence of CVD. Results In the longitudinal study, multiple regression analysis showed that basal serum ADMA level had a significantly positive association with changes in IMT (β = 0·35, P = 0·03) independently of age, duration of diabetes, BMI, blood pressure, low‐density lipoprotein and high‐density lipoprotein (LDL and HDL) cholesterol, HbA_1c, and renal function. In the cross‐sectional study, the serum ADMA level was significantly and positively associated with the presence of CVD (odds ratio = 7·22, 95% confidence interval 1·29–40·40, P = 0·02, by logistic analysis) and with baPWV (β = 0·14, P < 0·01, by multiple regression analysis). In contrast, serum symmetric dimethylarginine level, a structural isomer of ADMA, was associated neither with parameters for atherosclerosis nor with the presence of CVD in both studies. Conclusions Serum ADMA is a predictor of atherosclerosis and associated with the presence of CVD in Japanese patients with type 2 diabetes mellitus.     

Asymmetric dimethylarginine is associated with carotid atherosclerosis in patients with essential hypertension

Abstract

This study was to assess the relationship between asymmetric dimethylarginine (ADMA) and carotid atherosclerosis in patients with essential hypertension. A total of 182 individuals with never-treated essential hypertension and 182 age-matched healthy controls were studied. Plasma ADMA levels, mean intima-media thickness (IMT) and plaque score were significantly greater in hypertensive patients than normotensive controls. ADMA was positively correlated with mean IMT. On multiple logistic regression analysis, ADMA was a crucial independent predictor of carotid plaque formation (plaque score ≥1.1). Our results suggest that increased levels of ADMA are associated with the development of carotid atherosclerosis in hypertensive patients.     

Uncomplicated type 1 diabetes is associated with increased asymmetric dimethylarginine concentrations

CONTEXT: Asymmetric dimethylarginine (ADMA) has recently emerged as an independent risk marker for cardiovascular disease, but studies investigating the ADMA levels in type 1 diabetes mellitus (DM) are scarce. OBJECTIVE: We aimed to evaluate plasma ADMA, L-arginine concentrations, and L-arginine to ADMA ratio in uncomplicated type 1 diabetic patients and controls. DESIGN AND SUBJECTS: Forty patients with type 1 DM who did not have clinical evidence of vascular complications and 35 healthy controls were included in the study. RESULTS: Plasma ADMA concentrations were higher (2.6 +/- 1.9 vs. 1.7 +/- 0.7 micromol/liter, P < 0.01), and L-arginine levels were lower (79.3 +/- 22.6 vs. 89.6 +/- 19.4 micromol/liter, P < 0.05) in the diabetic group, compared with controls. The L-arginine to ADMA ratio was also lower in the diabetic group (38.7 +/- 17.1 vs. 62.0 +/- 27.9, P < 0.0001). In diabetic patients, logADMA correlated positively with body mass index (BMI) (P = 0.01), fasting blood glucose (P = 0.006), and low-density lipoprotein cholesterol (LDL-c) (P = 0.01) and negatively with high-density lipoprotein cholesterol (P = 0.03). L-arginine to ADMA ratio correlated negatively with BMI (P = 0.004), fasting blood glucose (P = 0.02), and LDL-c (P = 0.01) and positively with high-density lipoprotein cholesterol (P = 0.04). In controls, logADMA and L-arginine to ADMA ratio correlated with BMI and LDL-c (P < 0.05). In regression analysis, BMI predicted 15% variance of ADMA levels (P = 0.02). CONCLUSIONS: We demonstrated that ADMA increases and L-arginine to ADMA ratio decreases, even before the development of vascular complications in type 1 DM.     

2型糖尿病患者总同型半胱氨酸水平影响因素分析

目的:探讨2型糖尿病(DM)患者总同型半胱氨酸(tHcy)水平的影响因素.方法:随机选择308例患者,根据血糖分组:正常血糖组(Ⅰ组)109例,糖耐量减低组(Ⅱ组)75例,2型DM组(Ⅲ组)124例.所有患者均测量tHcy、身高、体重、腰围、血压、血脂、血糖、胰岛素及肌酐水平.结果:Ⅲ组和Ⅱ组的tHcy高于Ⅰ组,差异有统计学意义(P＜0.05).多元线性回归分析表明:tHcy与IR、肌酐呈正相关(β=0.158,P=0.022;β=0.163,P=0.029);男性tHcy水平高于女性(β=-0.164,P=0.03).结论:性别、肌酐水平、IR是同型半胱氨酸水平的影响因素.     

CD2AP is associated with end-stage renal disease in patients with type 1 diabetes

CD2-associated protein (CD2AP) is essential for podocyte function. CD2AP mutations have been found in patients with focal segmental glomerulosclerosis, a disease histologically resembling diabetic nephropathy and often progressing to end-stage renal disease (ESRD). We hypothesised that variations in the CD2AP gene may contribute to susceptibility to glomerular injury in diabetes and investigated if single-nucleotide polymorphisms (SNPs) in CD2AP are associated with diabetic nephropathy in patients with type 1 diabetes. The discovery cohort consisted of 2,251 Finnish patients with type 1 diabetes. SNPs were selected from the HapMap database to cover the CD2AP gene. The associations between genotyped SNPs and diabetic nephropathy or ESRD were analysed with the chi-squared test and logistic regression. Three SNPs were selected for replication in cohorts from Denmark, Italy, the United Kingdom and Ireland. None of the 15 successfully genotyped SNPs were associated with diabetic nephropathy when compared to patients with normal albumin excretion rate. However, when genotype frequencies in patients with ESRD were compared with all other patients, two CD2AP SNPs, rs9369717 and rs9349417, were found to be associated with ESRD. The meta-analysis of the original and two additional European cohorts resulted in significant p values <0.01 for these SNPs. A third SNP, rs6936632, was suggestively associated with ESRD in the Finnish patients and in the meta-analysis of four cohorts. CD2AP gene variants may contribute to susceptibility to ESRD in patients with type 1 diabetes.     

Ischemic heart disease is associated with vertebral fractures in patients with type 2 diabetes mellitus

Aims/Introduction

Discordant results about the relationship between diabetes complications and the risk of fragility fractures have been reported. Our aims were to analyze the factors related to morphometric vertebral fractures (VFs) in patients with type 2 diabetes mellitus, and to explore the association between the presence of VFs and the main cardiovascular risk factors.

Materials and Methods

We carried out a cross‐sectional study including 123 patients with type 2 diabetes mellitus, and in 72 of these patients we recorded data about the risk factors for VFs and comorbidities of diabetes including diabetes‐related microvascular disease and cardiovascular disease.

Results

In the crude analysis, diabetic retinopathy (odds ratio [OR] 4.09, 95% confidence interval [CI] 1.01–12.5), ischemic heart disease (OR 5.02, 95% CI 1.1–9.7) and waist circumference (OR 1.06, 95% CI 1.006–1.114) were related to VFs. In the full model (adjusted for age, sex, body mass index), ischemic heart disease was the only determinant of VF (OR 3.33, CI 1.02–10.91, P = 0.047); whereas diabetic retinopathy did not reached significance (OR 2.27, CI 0.71–7.27, P = 0.16).

Conclusions

In summary, ischemic heart disease is associated with an increased risk of VFs in type 2 diabetes mellitus.     

老年2型糖尿病患者中同型半胱氨酸与炎症相关细胞因子的检测

目的 探讨老年2型糖尿病（T2DM）大血管病变患者血清总同型半胱氨酸（they）水平与炎症相关细胞因子间的关系。方法135例老年T2DM患者分为2组：无大血管并发症组（71例）和T2DM合并大血管病变组（64例）;32例体检正常老人作为正常对照组（CTR）。酶联免疫吸附试验（enzyme linked immunosorbentassay,ELISA）法检测受试者血清中tHey、白细胞介素2（IL-2）、IL-4、IL-6、IL-8、IL—10、IL-18和γ-干扰素（INF-7）水平。对各指标的组间差异进行统计学分析。结果与正常对照组比较,T2DM患者血清tHey、IL-2、IL-6、IL-8、IL-18和INF-γ显著升高,IL—10显著降低（P〈0．05）;T2DM合并大血管病变组tHcy、IL-6、IL-8、IL-18和INF-γ显著高于无大血管病变组（P〈0．05）;IL-6、IL-8、IL-18与tHey呈正相关（r=0．33、0．49、0．27,P〈0．01、0．01、0．05）。结论老年糖尿病患者tHey、IL．2、IL-6、IL-8、IL—18、和INF-γ显著高于正常老年人;测定这些指标可能对T2DM患者的血管病变起辅助诊断作用。     

非对称性二甲基精氨酸与糖尿病脑血管病变

一氧化氮(nitric oxide,NO)是已知最重要的内源性血管舒张因子.内皮型一氧化氮合酶(nitric oxide and enzyme,NOS)的竞争性抑制剂非对称性二甲基精氨酸(asymmetric dimethylarginine,ADMA)可抑制NO的合成,使NO/NOS通路发生障碍,NO合成减少.近年来的研究表明,ADMA与糖尿病脑血管病变的发生和发展有关,为进一步明确该病的发生机制提供了新的见解.     

2型糖尿病并发抑郁症患者血清同型半胱氨酸水平升高

目的 探讨血清同型半胱氨酸(Hcy)水平与2型糖尿病(T2DM)并发抑郁症的关系.方法 338例T2DM患者中,根据临床表现和汉密尔顿抑郁量表(HRSD)诊断抑郁症患者101例,根据HRSD评分评定其抑郁程度,分为轻、中、重三组.测定血清Hcy、FPG、HbA1c.结果 T2DM患者Hcy水平显著高于对照组;糖尿病并发抑郁症患者血清Hcy水平显著高于非抑郁症组,抑郁症组有更高的HbA1c(P＜0.01),两组FPG水平无统计学差异.糖尿病并发抑郁症的轻、中、重三组比较, HRSD评分与Hcy、HbA1c水平呈显著正相关.结论 高Hcy血症可能是糖尿病患者抑郁症发病的重要危险因素.     

The association of diabetic microvascular and macrovascular disease with cutaneous circulation in patients with type 2 diabetes mellitus

Aims

To study the impact of diabetic neuropathy, both peripheral sensorimotor (DPN) and cardiac autonomic neuropathy (CAN), on transcutaneous oxygen tension (TcPO₂) in patients with type 2 diabetes mellitus (T2DM).

同型半胱氨酸与新诊2型糖尿病下肢血管病变的关系

目的探讨同型半胱氨酸（Hcy）与新确诊2型糖尿病（T2DM）下肢血管病变的关系。方法测定正常对照组（NC）、新确诊T2DM但无下肢血管病变组（T2DM）、新确诊T2DM并伴有下肢血管病变组（T2DM＋LLVD）Hcy和踝肱指数（ABI）的变化。结果与NC组相比,T2DM组和T2DM＋LLVD组BMI、WHR、SBP、TC、TG、LDL-C、HbA1c显著升高,HDL-C显著下降;与T2DM组相比,T2DM＋LLVD组Hcy、LDL-C、HbA1c显著升高,HDL-C显著下降。Logisitic回归分析显示Hcy是新确诊T2DM并伴有下肢血管病变的独立危险因子。结论Hcy升高是促使新确诊T2DM并发下肢血管病变的独立危险因素。     

Circulating homocysteine levels in patients with type 2 diabetes mellitus

Background and aimPrevious studies have shown conflicting results regarding circulating homocysteine levels in patients with type 2 diabetes.Methods and resultsThis observational study included 2121 patients with angiographically proven coronary artery disease (507 patients with type 2 diabetes and 1614 patients without diabetes). Circulating homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, renal function, presence of coronary artery disease (CAD) diagnosed by coronary angiography, and circulating folate and vitamin B₁₂ status were assessed. Plasma homocysteine levels [median (25th; 75th percentile)] were significantly higher in patients with diabetes than in those without [12.4 μmol/L (9.9 μmol/L; 15.9 μmol/L) versus 11.7 μmol/L (9.6 μmol/L; 14.5 μmol/L), P = 0.011]. Diabetes affected homocysteine levels only in patients with a glomerular filtration rate <90 mL/min [13.0 μmol/L (10.5 μmol/L; 16.7 μmol/L) in patients with diabetes versus 12.2 μmol/L (10.1 μmol/L; 15.2 μmol/L) in patients without diabetes, P = 0.006] but not in those with a glomerular filtration rate ≥90 mL/min [10.1 μmol/L (8.1 μmol/L; 12.4 μmol/L) versus 10.2 μmol/L (8.8 μmol/L; 12.3 μmol/L), P = 0.267]. Multivariable analysis did not show an independent association between diabetes and homocysteine level (P = 0.342).ConclusionCirculating homocysteine levels are increased in patients with type 2 diabetes compared with non-diabetic patients due to a more diabetes-associated adverse risk profile rather than to diabetes itself.     

Metformin treatment lowers asymmetric dimethylarginine concentrations in patients with type 2 diabetes

This study was initiated to see if plasma asymmetric dimethylarginine (ADMA) concentrations decreased in hyperglycemic patients with type 2 diabetes following metformin treatment, either as monotherapy or following its addition to sulfonylurea-treated patients. Fasting plasma glucose, dimethylarginine, and L-arginine concentrations were measured before and 3 months after the administration of a maximally effective dose of metformin to 31 patients with type 2 diabetes in poor glycemic control (fasting plasma concentrations > 9.7 mmol/L), while being treated with either diet (n = 16) or a maximal amount of a sulfonylurea compound (n = 15). Fasting plasma glucose concentration (mean +/- SEM) decreased to a similar degree (P <.01) in patients treated with either metformin alone (12.4 +/- 0.5 to 9.5 +/- 0.5 mmol/L) or when it was added to a sulfonylurea compound (14.1 +/- 0.5 to 10.6 +/- 0.9 mmol/L). The improvement in glycemic control was associated with similar decreases (P <.01) in ADMA concentrations in metformin (1.65 +/- 0.21 to 1.18 +/- 0.13 micromol/L) and sulfonylurea + metformin-treated patients (1.75 +/- 0.13 to 1.19 +/- 0.08 micromol/L). Plasma L-arginine concentrations were similar in the 2 groups at baseline and did not change in response to metformin. Thus, metformin treatment was associated with a favorable increase in the plasma L-arginine/ADMA ratio. These results provide the first evidence that plasma ADMA concentrations decrease in association with improved glycemic control in patients with type 2 diabetes and demonstrate that the magnitude of the change in metformin-treated patients was similar, irrespective of whether it was used as monotherapy or in combination with sulfonylurea treatment.     

2型糖尿病及合并大血管病变糖尿病患者C反应蛋白水平观察

目的　观察C反应蛋白 (CRP)在 2型糖尿病 (DM )及DM合并大血管病变时的浓度变化。方法　用ELISA方法测定血清CRP水平。在 2型DM患者 (伴或不伴大血管病变 )、无糖尿病的大血管病变患者、空腹血糖受损 (IFG)者、糖耐量低减 (IGT)者以及正常对照组测定血清CRP水平。结果　IGT者、2型DM以及无糖尿病的大血管病变患者血清CRP水平明显增高 (P <0 .0 5～ <0 .0 0 1) ;2型DM伴有或不伴有大血管病变患者以及无糖尿病的大血管病变患者间血清CRP水平差异无显著性 ;大血管病变患者血清CRP水平较非大血管病变者明显增高 (P <0 .0 5 )。结论　CRP在 2型DM和动脉粥样硬化的发生发展中均具有致病作用 ;就致动脉粥样硬化而言 ,CRP是普通人群 (包括 2型DM )的一般危险因子 ,并非 2型DM的特殊危险因子。     

Long-term effects of cilostazol on the prevention of macrovascular disease in patients with type 2 diabetes mellitus

We analyzed the medical records of 884 type 2 DM patients who were taking different antiplatelet agents for more than 2 years. Based on the records, occurrences of cardiovascular events for 10 years were evaluated. The composite disease-free survival rate for cilostazol monotherapy group was similar to aspirin subgroup (p = 0.133).     

中老年2型糖尿病女性患者大血管病变相关危险因素分析

目的 探讨中老年T2DM女性患者大血管病变的相关危险因素. 方法 将165例T2DM女性患者分为合并大血管病变（A）组和未合并大血管病变（B）组,对两组的临床特征及相关血液检查指标行Logistic回归分析. 结果 Logistic回归分析显示,年龄（OR=1.076,95％CI：1.029～1.124,P=0.001）、SBP（OR=1.026,95％CI：0.999～1.053,P=0.060）和TC（OR=1.516,95％ CI：0.988～2.325,P=0.057）进入回归方程. 结论 年龄、SBP和TC为中老年T2DM女性患者大血管病变的独立危险因素.