Serum levels of advanced glycation end products are increased in patients with type 2 diabetes and coronary heart disease.

OBJECTIVE: To investigate whether serum levels of advanced glycation end products (AGEs) and the glycoxidation product Nepsilon-(carboxymethyl)lysine (CML) are increased in patients with type 2 diabetes compared with nondiabetic control subjects and whether levels of AGEs and/or CML differ in patients with type 2 diabetes with or without coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: Serum levels of AGEs and CML were measured with an immunoassay in 32 men and 21 women aged 59.3+/-6.2 years (means +/- SD) with type 2 diabetes for 7.3 + 3.1 years and in 17 men and 17 women aged 56.2+/-4.2 years without diabetes. Of the patients with diabetes, 18 had CHD. RESULTS: The serum levels of AGEs and CML were significantly increased in patients with type 2 diabetes compared with nondiabetic control subjects (median [5th-95th percentile]: AGEs 7.4 [4.4-10.9] vs. 4.2 [1.6-6.4] U/ml, P < 0.0001; CML 15.6 [5.6-29.9] vs. 8.6 [4.4-25.9] U/ml, P < 0.0001). The median level of AGEs but not CML was significantly increased in patients with type 2 diabetes and CHD compared with patients without CHD (8.1 [6.4-10.9] vs. 7.1 [3.5-9.8] U/ml, P = 0.03). There were significant positive correlations between serum levels of AGEs and CML in both patients and control subjects. CONCLUSIONS: Levels of AGEs and CML were significantly increased in patients with type 2 diabetes compared with nondiabetic control subjects, and levels of AGEs but not CML were significantly higher in patients with type 2 diabetes and CHD than in patients without diabetes. These results may indicate a role for non-CML AGEs in the development of macrovascular disease in patients with type 2 diabetes.     

Anemia and type 2 diabetes mellitus associated with peripheral arterial disease progression in Chinese male patients

ObjectivePeripheral arterial disease (PAD) is a chronic occlusive disease mainly occurred in elderly adults. Arteriosclerosis obliterans (ASO) mainly occurring from small or medium sized arteries of the lower extremities is one of the most common causes of PAD. The gender-related differences of circulating risk factors in diabetic patients with ASO in China remain unknown. The aim of this study is to investigate the gender-related differences in the pattern of several potential risk factors between male and female patients with ASO and type 2 diabetes mellitus (T2D).Design and methodsClinical profiles and risk factors were analyzed in 323 Chinese patients with ASO and 112 patients were confirmed with T2D. Severities of limb ischemia were staged according to Fontaine classification.ResultsThe significant inverse correlation was seen between the increased age and hemoglobin. The significant positive correlation was seen between the increased age, urea and creatinine both in the non-diabetic and diabetic male patients. The expression levels of hemoglobin significantly correlate with the classification of Fontaine clinical symptoms in Chinese male patients with T2D/ASO.ConclusionThe study is the first report indicating that the gender-related differences of circulating risk factors are associated with T2D patients with ASO in China. Anemia in Chinese male patients with T2D/ASO may play an important role in peripheral arterial disease progression.     

Homocysteine levels are associated with the severity of peripheral arterial disease in Type 2 diabetic patients

Summary.  Background : Homocysteine levels are positively associated with the risk of cardiovascular disease. They might be determined by both MTHFR677C→T polymorphisms and folate or B-vitamin status. Objectives : To investigate the possible association between plasma homocysteine levels and its genetic or environmental determinants and either the presence or the severity of peripheral arterial disease (PAD), in Type 2 diabetic patients. Methods : From a cohort of 944 patients with Type 2 diabetes, 135 patients with PAD were selected, and frequency-matched for age and sex with 219 Type 2 diabetic control patients without macrovascular complications. According to the increasing severity of the disease, patients were divided into PAD₁ (only diffuse calcifications of the arteries without any stenosis or occlusion), PAD₂ (one or two stenosis or occlusions) and PAD₃ (three or more). Results : Homocysteine levels were similar in control and case patients (10.3 µmol L⁻¹ vs. 10.7 µmol L⁻¹, P  = 0.53); however, a significant increase was found in PAD₃ patients: odds ratio = 2.77 (95% confidence interval 1.14, 6.72) for patients with homocysteine levels above the median vs. those under the median in multivariate analysis. Although all significantly associated with homocysteine levels, neither MTHFR genotype nor folic acid or vitamin B₁₂ levels were associated with severity of PAD. A significant interaction ( P  < 0.05) was found between folic acid and MTHFR polymorphism in determining the levels of homocysteine. Conclusions : In Type 2 diabetes, homocysteine was associated with the angiographic severity of PAD, but neither the genotypes nor vitamin levels contributed to this association.     

2型糖尿病老年患者周围动脉病变的发病率及相关因素研究

目的观察2型糖尿病老年患者周围动脉病变发病情况并探讨其相关影响因素。方法采用横断面调查研究方法,收集328例2型糖尿病老年患者相关临床资料,按照踝臂指数≤0.9或>1.3为异常、0.9～1.3为正常分组。采用单因素和多因素Logistic回归分析确定2型糖尿病老年患者周围动脉病变的风险因素。结果全部老年患者中周围动脉病变者共93例,占28.35%;正常者共235例,占71.65%。周围动脉病变组老年患者年龄(69.59±10.45)岁、病程(2.47±0.91)年、收缩压(146.60±20.93)mmHg、舒张压(97.77±17.01)mmHg、空腹血糖(11.44±3.78)mmol/L、HbA1c(10.66±2.56)%、TG(1.78±0.44)mmol/L、TC(4.92±1.52)mmol/L、LDL-C(4.42±0.97)mmol/L、尿素(6.81±2.72)mmol/L、血尿酸(372.28±109.42)μmol/L、红细胞体积(90.48±12.46)fl均高于正常组,且差异具有统计学意义(t=2.16,P=0.031;t=3.71,P<0.001;t=3.75,P<0.001;t=2.79,P=0.006;t=5.46,P<0.001;t=4.81,P<0.001;t=2.14,P=0.033;t=2.35,P=0.019;t=3.18,P=0.002;t=2.3,P=0.022;t=3.17,P=0.002;t=3.51,P<0.001)。多因素Logistic回归分析发现:年龄(≥75岁)、收缩压(≥140mmHg)、空腹血糖(>6.1mmol/L)、LDL-C(>3.3mmol/L)、血尿酸(>432μmol/L)、红细胞体积(>100fl)为周围动脉病变的独立风险因素。结论踝臂指数是早期诊断周围动脉病变的有效无创手段,高龄、高血压、空腹血糖升高、LDL-C升高、高尿酸血症、红细胞体积增大是2型糖尿病老年患者周围动脉病变的风险因素。     

2型糖尿病患者外周血管病变的临床研究

目的探讨2型糖尿病患者外周动脉病变（PAD）的发生率及其危险因素。方法利用Huntleig Healthcare糖尿病足诊断箱检测我院184例2型糖尿病的ABI和PBI,同时检测血压、血小板、血脂、尿酸、HBA1C等相关指标,通过统计学方法探讨影响ABI的相关因素。结果ABI降低组（ABI〈0．90）40例（21．74％）,ABI升高组（ABI≥1．30）23例（12．5％）,ABI正常者（0．90≤ABI〈1.30）121例（65．76％）。与ABI正常组比较,ABI降低组患者病程及住院天数更长,吸烟率、HBA1C、SBP、2HPG、TC、LDL—C、血小板计数更高;病程、SBP、HBA1C、2HPG是ABI升高的危险因素。ABI异常组糖尿病的合并症及心脑血管事件的几率增高。结论ABI诊断T2DM伴PAD简便实用可靠,病程、高血脂、吸烟史、高血糖、高血压和高凝状态是PAD的主要危险因素。     

Serum 1,5-anhydroglucitol levels in patients with fulminant type 1 diabetes are lower than those in patients with type 2 diabetes

ObjectivesWe investigated clinical relevance of serum 1,5-anhydroglucitol (1,5-AG) levels in fulminant type 1 diabetes mellitus (FT1DM) patients, because 1,5-AG is known to reflect short term glycemic control.Design and methodsSubjects comprised 7 patients with FT1DM and 32 patients with type 2 diabetes mellitus (T2DM) with HbA1c < 8.5%. All of them have never been treated for diabetes.ResultsHbA_1C showed no significant difference between both groups. On the other hand, serum 1,5-AG levels were significantly lower in the FT1DM patients than in the T2DM patients. Serum 1,5-AG levels were < 5.0 μg/ml in 6 of 7 (86%) FT1DM patients, compared with only 1 of 32 (3%) T2DM patients.ConclusionsSerum 1,5-AG levels were lower in the FT1DM patients than in the T2DM patients. Serum 1,5-AG, but not HbA_1C, reflects short-term exacerbation of glycemia in patients with FT1DM.     

2型糖尿病合并周围神经病变内皮素及一氧化氮水平监测

目的探讨血浆内皮素(ET)及血清一氧化氮(NO)在2型糖尿病合并周围神经病变时的浓度变化。方法糖尿病合并周围神经病变组36例,糖尿病无周围神经病变组30例,正常对照组30例。结果DPN组ET水平显著高于DM组(P<0·001),DM组ET水平显著高于正常对照组(P<0·001)。DPN组NO水平显著低于DM组(P<0·001),DM组NO水平显著低于正常对照组(P<0·001)。直线相关分析显示ET与NO呈负性相关。结论ET、NO的检测作为血管内皮受损的指标,对DPN的发生及病情的判断有参考价值。     

Diabetic peripheral neuropathy is associated with increased arterial stiffness without changes in carotid intima-media thickness in type 2 diabetes

OBJECTIVE

This study was conducted to investigate the association of diabetic peripheral neuropathy (DPN) with both arterial stiffness and intima–media thickness (IMT).

RESEARCH DESIGN AND METHODS

We conducted a cross-sectional analysis of 731 subjects with type 2 diabetes. DPN was diagnosed on the basis of neuropathic symptoms, insensitivity to a 10-g monofilament, abnormal pin-prick sensation, and abnormal current perception threshold. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI), and IMT was assessed by B-mode ultrasonography.

RESULTS

Patients with DPN had higher CAVI than those without DPN in multivariate-adjusted models, whereas no differences in IMT were observed between patients with and without DPN after adjustment for age and sex. In the multivariate analysis, CAVI was a significant determinant of DPN (odds ratio 1.36 [95% CI 1.13–1.65], P = 0.001).

CONCLUSIONS

DPN is significantly associated with arterial stiffness without carotid intimal changes in patients with type 2 diabetes.The leading cause of death in patients with diabetes is cardiovascular disease (CVD) (1); recent studies have reported that microvascular disease is also associated with excess mortality (2). Although the underlying mechanism is unclear, some evidence suggests that the effects of microvascular disease on mortality may be linked to subclinical atherosclerosis, considering atherosclerotic vascular changes in parallel with microvascular complications, including retinopathy (3), nephropathy (4), and autonomic neuropathy (5).Diabetic peripheral neuropathy (DPN) is a common microvascular complication with high mortality rates (6), but little is known about the association between DPN and atherosclerotic vascular changes. Thus, we investigated the association between DPN and vascular wall properties in patients with type 2 diabetes by measuring cardio-ankle vascular index (CAVI) and carotid intima–media thickness (IMT).     

Development of new peripheral arterial occlusive disease in patients with type 2 diabetes during a mean follow-up of 11 years

OBJECTIVE: To assess the occurrence and development of new peripheral arterial occlusive disease (PAOD), its risk factors, and the outcome in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 130 type 2 diabetic patients (mean age 58 years) were examined at baseline and after a mean follow-up of 11 years (range 7-14). The ankle-brachial index (ABI) and toe-brachial index were used to detect PAOD. Blood and urine samples were taken at baseline, and a history of cardiovascular events was recorded during follow-up. RESULTS: PAOD was diagnosed in 21 (16%) patients at baseline. During follow-up, 21 of 89 (24%) patients developed new PAOD. There were 29 patients who died, 21 (72%) of them from cardiovascular disease. Patients with PAOD suffered an excess mortality compared with patients without PAOD (58 vs. 16%; P < 0.001). Logistic regression analysis showed that PAOD at baseline was associated with age, duration of diabetes, smoking, and urinary albumin excretion rate. Patients who developed new PAOD during follow-up had higher serum LDL cholesterol concentrations and lower HDL cholesterol concentrations and were older than the patients who remained free of PAOD. CONCLUSIONS: Objectively measured PAOD is frequent in type 2 diabetic patients. It presents the early clinical signs of atherosclerosis and is strongly associated with cardiovascular death. The risk factor pattern for PAOD was different at baseline and after a mean follow-up of 11 years. We consider routine ABI measurements and modification of risk factors necessary also in patients with asymptomatic PAOD.     

Postprandial apolipoprotein B48 is associated with asymptomatic peripheral arterial disease: A study in patients with type 2 diabetes and controls

BackgroundPostprandial hyperlipidemia is a common feature in type 2 diabetes; our aim was to investigate whether there is an association between subclinical peripheral arterial disease (PAD) and the levels of apolipoprotein B48, as a specific marker for postprandial lipidemia.MethodsWe enrolled 101 patients with type 2 diabetes and 73 controls free from clinical cardiovascular disease. Main outcome measures were the presence of subclinical PAD, assessed by the ankle-brachial index, and the intestinal particles measured as the concentration of apolipoprotein B48 at fasting and 4 h after a mixed breakfast.ResultsNo control had subclinical PAD. Of the 101 diabetic patients, 21 had subclinical PAD. The levels of apo B48, both fasting and postprandial, were only significantly raised in the diabetic patients who had PAD. The diabetic patients without vascular disease had similar concentrations of triglycerides and apo B48 to the controls. In binary logistic regression analyses, only smoking and postprandial B48 levels, in addition to diabetes, were independently associated with PAD. On the other hand, PAD but not diabetes was associated with the fasting and postprandial levels of apo B48.ConclusionOur study suggests that apolipoprotein B48 levels might be a marker of occult PAD in patients suffering from type 2 diabetes mellitus. Accordingly, subclinical PAD should be taken into account in studies on postprandial lipidemia involving patients with diabetes.     

Serum interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes

OBJECTIVE: Interleukin (IL)-18 is a proinflammatory cytokine secreted from mononuclear cells. Serum concentration of IL-18 is a strong predictor of death in patients with cardiovascular diseases. Recent studies have shown that microinflammation is involved in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases. This study aimed to test the hypothesis that the serum level of IL-18 is a common predictor of nephropathy and atherosclerosis in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Eighty-two Japanese patients with type 2 diabetes and 55 age- and sex-matched healthy control subjects were enrolled. Patients with renal dysfunction (creatinine clearance <1 ml/s) were excluded. We assessed clinical parameters and measured serum and urinary IL-18 levels, serum IL-6 levels, carotid intima-media thickness (IMT), and brachial-ankle pulse wave velocity (baPWV) in all patients. Further, we evaluated changes of urinary albumin excretion rate (AER) after 6 months in 76 diabetic patients. RESULTS: Serum and urinary IL-18 levels were significantly elevated in patients with type 2 diabetes as compared with control subjects (serum IL-18 179 +/- 62 vs. 121 +/- 55 pg/ml, P < 0.001; urinary IL-18 97 +/- 159 vs. 47 +/- 54 pg/ml, P = 0.035). Univariate linear regression analysis showed significant positive correlations between serum IL-18 and AER (r [correlation coefficient] = 0.525, P < 0.001), HbA(1c) (r = 0.242, P = 0.029), high-sensitivity C-reactive protein (hs-CRP) (r = 0.240, P = 0.031), and urinary beta-2 microglobulin (r = 0.235, P = 0.036). Serum IL-18 levels also correlated positively with carotid IMT (r = 0.225, P = 0.042) and baPWV (r = 0.232, P = 0.040). We also found a significant correlation between urinary IL-18 and AER (r = 0.309, P = 0.005). Multivariate linear regression analysis showed that AER (standard correlation coefficients [B] = 0.405, P < 0.001) and hs-CRP (B = 0.207, P = 0.033) were independently associated with serum IL-18 levels. AER was also independently associated with urinary IL-18 levels (B = 0.295, P = 0.005). Moreover, serum and urinary IL-18 levels correlated positively with AER after 6 months (r = 0.489, P < 0.001 and r = 0.320, P = 0.005) and changes in AER during the follow-up period (r = 0.268, P = 0.018 and r = 0.234, P = 0.042). CONCLUSIONS: Serum levels of IL-18 might be a predictor of progression of diabetic nephropathy as well as cardiovascular diseases.     

Circulating levels of nitrated apolipoprotein A-I are increased in type 2 diabetic patients.

Recent work has shown that high-density lipoprotein (HDL) isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of 3-nitrotyrosine and 3-chlorotyrosine. A higher nitrotyrosine content in lipoprotein is significantly associated with diminished cholesterol efflux capacity of the lipoprotein. Since accelerated atherogenesis is a key complication of diabetes mellitus, and nitrosative stress has recently been implicated in diabetic pathology, we set out to demonstrate an increase in the circulating levels of nitrated apolipoprotein A (apoA)-I in type 2 diabetic patients and its putative correlation with metabolic biomarkers. In this work we addressed this hypothesis in a case-control study with 30 type 2 diabetic patients and 30 age-matched control subjects. Nitrated apoA-I was 3280+/-1910 absorbance peak area/apoA-I (g/L) for diabetic patients and 2320+/-890 for control subjects (p<0.037). This represents a 50% increase in circulating nitrated apoA-I in diabetic patients to age-matched controls. Diabetic patients also showed increases of a similar magnitude in circulating advanced glycation endproducts measured as pentosidine fluorescence (44.16+/-16.26 vs. 30.84+/-12.86 AU; p<0.01) and in circulating lipoperoxides (46.0+/-18.0 vs. 37.2+/-18.0 nmol/L; p<0.03). No significant correlation was found between nitration of apoA-I and glycosylated hemoglobin or any of the other parameters measured. If proven in subsequent functional and in vivo studies, increased nitrated apoA-I would represent another mechanism by which nitrosative stress participates in diabetic macro-angiopathy.     

Rehabilitation in patients with peripheral arterial disease

Rehabilitation is a recommended first-line therapy for patients with peripheral arterial disease (PAD) and consists of supervised exercise training and therapeutic education. Proved benefits are significant: improve pain-free walking distance, functional status and quality of life; reduce cardiovascular risk factors and mortality. At least three sessions weekly are recommended during 3 months. Exercise conditioning (global training and lower limb resistance training) is tailored by the preliminary evaluation of walking ability (free walking test, treadmill tests, 6-min walk test) and of the cardiac tolerance (maximal effort tests). Then the exercise workload is progressively improved. The four main goals of therapeutic education are: smoking cessation, prolonged physical activity, Mediterranean diet and observing pharmacological therapies. The limited compliance of the patients with PAD is often an obstacle for educational needs. The chronic patients with important functional limitations and unchecked risk factors will be preferentially enrolled in such programs. When a revascularization is discussed, rehabilitation can serve as trial treatment. Despite its efficacy, rehabilitation is still underutilized in clinical practice and should be promoted.     

超敏C反应蛋白与初诊2型糖尿病下肢血管病变的相关性研究

目的 探讨超敏C反应蛋白(hsCRP)与初诊2型糖尿病(T2DM)下肢血管病变发生的关系.方法 测定正常对照组(A组)、初诊T2DM患者(B组)、初诊T2DM下肢血管病变患者(C组)的hsCRP水平和踝肱指数(ABI)变化.结果 与ABI正常的A组相比,ABI正常的B组和ABI降低的C组hsCRP、体质量指数、腰臀围比、收缩压、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、糖化血红蛋白(HbA1 c)显著升高或增加(P＜0.01或P＜0.05)、高密度脂蛋白胆固醇(HDL-C)显著下降(P＜0.05);C组hsCRP(1.10±0.36)vs(0.88±0.36)、LDL-C(4.20±1.09)mmol/L vs(3.25±1.04)mmol/L、HbAlc(10.11± 3.92)%vs(8.10±1.51)%明显高于B组(P＜0.01或P＜0.05),HDL-C明显低于B组(1.24±0.32)mmol/L vs(1.36±0.26)mmol/L(P＜0.05).logisitic回归分析显示,hsCRP是初诊T2DM下肢血管病变独立的危险因子(P=0.029).结论 hsCRP与初诊T2DM的发生相关,升高的hsCRP是促使初诊T2DM并发下肢血管病变的独立危险因素.     

Cerebral perfusion in patients with arterial hypertension associated with type 2 diabetes

The aim of the study was to assess cerebral perfusion (CP) in patients with arterial hypertension in combination with type II diabetes. The subjects were 57 patients with stage II AH (mean age 51.6 +/- 5.7 years), among who there were 33 patients without disturbances in carbohydrate exchange and 24 patients with compensated or subcompensated type II diabetes. All the patients underwent single-photon emission computed tomography of the brain with 99m Tchexamethylpropyleneamineoxime. The study showed that patients suffering from AH with or without type II diabetes had signs of cerebral hypoperfusion and lowered cerebrovascular reserve even in the absence of focal neurological symptoms. Disturbances in cerebral perfusion were more prominent in patients suffering from AH with type II diabetes vs. patients without carbohydrate exchange disorder.