Metabolic effects of telmisartan and irbesartan in type 2 diabetic patients with metabolic syndrome treated with rosiglitazone

BACKGROUND AND OBJECTIVE: Angiotensin II receptor blockers represent a class of effective and well-tolerated orally active antihypertensive drugs in the general hypertensive population and in diabetic patients. The aim of our study was to investigate the metabolic effects of telmisartan and irbesartan in diabetic subjects treated with rosiglitazone. METHODS: We evaluated 188 type 2 diabetic patients with metabolic syndrome. All patients took a fixed dose of 4 mg rosiglitazone/day. We administered 40 mg telmisartan/day or 150 mg irbesartan/day and evaluated their body mass index, glycosylated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment-index (Homa-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, adiponectin and resistin during 12 months of this treatment. RESULTS AND DISCUSSION: In addition to a comparable antihypertensive effect for telmisartan and irbesartan after 6 and 12 months, both treatments were associated with a significant reduction in TC and LDL-C plasma levels compared with baseline. After 6 months of treatment, only the telmisartan group experienced a significant improvement in (HbA(1c)), FPG, Homa-IR, adiponectin and resistin compared with the baseline values, whereas both drug regimens were associated with a significant improvement in these parameters after 12 months. However, the improvements observed in the telmisartan group were significantly larger than that noted in the irbesartan group after 12 months of treatment. FPI significantly decreased only after 12 months of treatment in both groups, but again, the reduction was significantly larger in the telmisartan-treated subjects. CONCLUSIONS: Telmisartan seemed to improve glycaemic and lipid control and metabolic parameters of the metabolic syndrome better than irbesartan. These differences could be relevant in the choice of therapy for this condition and diabetes.     

吡格列酮对2型糖尿病肾病患者骨桥蛋白和尿微量白蛋白的影响

目的:探讨吡格列酮对2型糖尿病(T2DM)早期肾病患者血清骨桥蛋白(OPN)及尿微量白蛋白/尿肌酐比值(UMA/Cr)的影响.方法:90例T2DM患者按照2009年ADA糖尿病指南以UMA/Cr分为单纯糖尿病组(DM,UMA/Cr＜ 30 μg/mg)30例、糖尿病肾病组(DN,UMA/Cr:30 ～ 299 μg/mg)60例,同时选择30名体检正常者为正常对照组.再将DN组随机分为吡格列酮组30例(吡格列酮30 mg/d+胰岛素,n=30)和安慰剂组30例(安慰剂+胰岛素,n=30),随访治疗3个月.所有对象均测定血糖、血脂、肾功能、C反应蛋白(CRP)、OPN和UMA/Cr等.结果:吡格列酮组治疗3个月后,UMA/Cr[(35.02±6.38) μg/mg vs(86.30±12.21) μg/mg、P＜0.01]、OPN[(394.24±19.43)ng/mL vs (457.00±15.21) ng/mL、P＜0.01]及HbA1c、TG、CRP与安慰剂组比较均显著降低,差异有统计学意义.相关性分析显示△UMA/Cr(△:治疗前-治疗后的差值)与血清△OPN(r=0.673,P=0.000)呈显著正相关.结论:T2DM肾病患者血清OPN水平升高.吡格列酮能减少UMA/Cr水平.其部分可能是通过降低血清OPN水平实现的.     

2型糖尿病患者合并代谢综合征空腹血浆游离脂肪酸的变化及其相关性分析

目的探讨2型糖尿病（T2DM）患者空腹游离脂肪酸（FFA）水平与代谢综合症（MS）的关系。方法按是否合并MS将T2DM患者分为MS组（A组150例）和非MS组（B组62例），与正常对照组（c组44例）分别比较空腹FFA水平，并进行相关性分析。结果A组较对照组FFA明显升高[（0.60±0.26）mmol／L vs（0.43±0.20）mmol／L，P〈0.01]，较B组FFA也明显升高[（0.60±0.26）mmol／L vs（0.50±0.i8）mmol／l，P〈0.01]，将腰围、总胆固醇（TCH）、低密度脂蛋白（LDL）、体重指数（BMI）、糖化血红蛋白（HbAlc）、年龄、性别进行多元回归分析显示：TG、BMI、LDL是影响血浆FFA水平的独立危险因素。结论T2DM合并MS人群空腹游离FFA水平明显升高，而FFA水平与TG、BMI等多种因素有关。     

Metformin-pioglitazone and metformin-rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndrome

BACKGROUND AND OBJECTIVE: Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin. The combination of metformin with thiazolidinediones is less well studied. The aim of the present study was to assess the differential effect, and tolerability, of metformin combined with pioglitazone or rosiglitazone on glucose, coagulation and fibrinolysis parameters in patients with type 2 diabetes mellitus and metabolic syndrome. METHODS: This 12-month, multicentre, double-blind, randomized, controlled, parallel-group trial was conducted at three study sites in Italy. We assessed patients with type 2 diabetes mellitus (duration >or=6 months) and with metabolic syndrome. All patients were required to have poor glycaemic control with diet, or experienced adverse effects with diet and metformin, administered up to the maximum tolerated dose. Patients were randomized to receive either pioglitazone or rosiglitazone self-administered for 12 months. We assessed body mass index (BMI), glycaemic control [glycosylated haemoglobin (HbA(1c)), fasting and postprandial plasma glucose and insulin levels (FPG, PPG, FPI, and PPI respectively), homeostasis model assessment (HOMA) index], lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG)], lipoprotein (a) [Lp(a)] and homocysteine (HCT) at baseline and at 3, 6, 9 and 12 months of treatment. RESULTS AND DISCUSSION: No BMI change was observed at 3, 6, 9 and 12 months in either group. Significant HbA(1c) decreases were observed at 9 and 12 months in both groups. After 9 and 12 months, mean FPG and PPG levels decreased in both groups. Decreases in FPI and PPI were observed at 9 and 12 months compared with the baseline in both groups. Furthermore, in both groups, the HOMA index improved but only at 12 months. Significant TC, LDL-C, HDL-C, TG improvement was present in the pioglitazone group at 12 months compared with the baseline values, and these variations were significantly different between groups. No TC, LDL-C, TG improvement was present in the rosiglitazone group after 12 months. Significant Lp(a) and HCT improvement was present in the pioglitazone group at 12 months compared with the baseline values, and Lp(a) change was significant compared with the rosiglitazone group. Significant HCT decrease was observed in the rosiglitazone group at the end of the study. In our type 2 diabetic patients, both drugs were safe and effective for glycaemic control and improving HCT plasma levels. However, long-term treatment with metformin plus pioglitazone significantly reduced Lp(a) plasma levels, whereas metformin + rosiglitazone did not. CONCLUSION: For patients with type 2 diabetes mellitus and metabolic syndrome, combined treatment with metformin and rosiglitazone or pioglitazone is safe and effective, However, the pioglitazone combination also reduced the plasma Lp(a) levels whereas the rosiglitazone combination did not.     

Effect of apolipoprotein E4 allele on plasma LDL cholesterol response to diet therapy in type 2 diabetic patients

OBJECTIVE: The aim of this study was to investigate the effect of apolipoprotein (apo)E4 allele on plasma LDL cholesterol response to calorie-restricted diet therapy in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Twenty-four diabetic patients with the apoE3/3 genotype and 11 diabetic patients with the apoE4/3 genotype were recruited. Participants were hospitalized for calorie-restricted diet therapy (25.0 kcal. kg body wt(-1). day(-1)) for 14 days. Body weight, fasting plasma glucose (FPG) levels, and plasma lipid levels on hospital days 1 and 14 were compared between the two apoE genotype groups. RESULTS: There were no significant differences in baseline FPG levels, HbA(1c) levels, BMI, and plasma levels of total cholesterol, triglyceride, and HDL cholesterol between the two apoE genotype groups, but baseline plasma levels of LDL cholesterol were significantly higher in the apoE4/3 group than in the apoE3/3 group. Body weight decreased slightly and FPG levels decreased significantly after diet therapy in both apoE genotype groups. In the apoE3/3 group, only plasma levels of triglyceride decreased significantly after diet therapy, whereas in the apoE4/3 group, plasma levels of triglyceride, total cholesterol, and LDL cholesterol decreased significantly after diet therapy. The decrease (percentage of change) in total cholesterol (-16.3 vs. -6.6%) and LDL cholesterol (-15.6 vs. -0.7%) after diet therapy was significantly greater in the apoE4/3 group than in the apoE3/3 group. CONCLUSIONS: Calorie-restricted diet therapy is more effective in reducing plasma LDL cholesterol in type 2 diabetic patients with the apoE4 allele.     

Significance of urinary type IV collagen in patients with diabetic nephropathy using a highly sensitive one-step sandwich enzyme immunoassay

Urinary concentrations of type IV collagen in patients with diabetic nephropathy were measured by a highly sensitive, one-step sandwich enzyme immunoassay. Samples from 298 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 80 healthy controls were examined. In diabetic patients with macroalbuminuria or renal insufficiency, the concentrations of urinary type IV collagen were significantly higher than those of diabetic patients with normoalbuminuria or healthy controls (P < 0.001). Urinary type IV collagen concentration in diabetic patients with microalbuminuria was significantly higher than that in diabetic patients with normoalbuminuria or that in healthy controls (P < 0.001). In contrast, there were no significant changes in the concentration of serum type IV collagen between microalbuminuric patients and normoalbuminuric patients. The area under the receiver operating characteristic (ROD) curve for the urinary type IV collagen concentration was equivalent to that of urinary albumin. It was concluded that urinary type IV collagen concentration determined using this method might be a useful marker for the early detection of diabetic nephropathy. J. Clin. Lab. Anal. 11:110–116. © 1997 Wiley-Liss, Inc.     

Microalbuminuria and the metabolic syndrome and its components in the Chinese population

BACKGROUND: Microalbuminuria and the metabolic syndrome (MetS) have both been linked to chronic kidney disease and cardiovascular disease. This study investigated the association between urinary albumin-to-creatinine ratio (ACR) and MetS and its components. MATERIALS AND METHODS: A total of 2311 subjects aged 40 years and over were recruited in 2004 in a metropolitan city in Taiwan. The biochemical indices, such as fasting glucose levels, urinary albumin, urinary creatinine and anthropometric indices, were measured. We defined microalbuminuria as a urinary ACR ranging from 30 to 300 mg g(-1) creatinine. MetS was defined using the American Heart Association and the National Heart, Lung and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF) definitions. The relationship between MetS and microalbuminuria was examined using multiple logistical regression analysis. RESULTS: Subjects with microalbuminuria had higher age, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose, triglycerides, total cholesterol (TCHOL)/high-density lipoprotein cholesterol (HDL-C) ratio, prevalence of diabetes mellitus and hypertension and lower HDL-C than subjects with normoalbuminuria. After adjusting for age and BMI, microalbuminuria was associated with the individual components of MetS, except in central obesity in women and elevated fasting glucose in men. After adjusting for age, BMI, smoking and alcohol consumption status, multiple logistical regressions revealed that microalbuminuria is strongly associated with MetS in both genders and according to both definitions. The odds ratio of having MetS using the AHA/NHLBI and IDF definition was 1.76 (1.16-2.67) and 1.73 (1.06-2.83) in men and 2.19 (1.38-3.50) and 2.09 (1.24-3.51) in women, respectively. CONCLUSIONS: Microalbuminuria was strongly associated with MetS and its components. There is an increased likelihood of having MetS if subjects have microalbuminuria.     

938例糖尿病足病变严重程度与糖尿病肾病分期研究

目的探讨糖尿病足Wagner分级（1～5级）与糖尿病肾病分期（Ⅰ～Ⅴ）之间的相关性。方法 2001年1月至2008年6月期间在天津医科大学代谢病医院足病科住院的938例2型糖尿病合并糖尿病足病的患者为研究对象,根据Wagner分级分为足病较轻组（Wagner 1～2级组）和足病较重组（Wagner 3～5级组）,入院时留取24小时尿测量微量白蛋白（MAU）。结果糖尿病足病较重组与足病较轻组相比,糖化血红蛋白（HbA1c）和MAU水平明显增高,分别为HbA1c（9.63±2.37）%vs（9.12±2.05）%（P〈0.01）;MAU[43.85（90.40）]mg/d vs[27.50（59.35）]mg/d（P〈0.01）;足病较重组患有严重肾病（Ⅳ～Ⅴ期）的发生率明显高于糖尿病足病较轻组（30.8%vs 23.5%,P〈0.05）。结论糖尿病足病变严重程度较高者严重肾病发生率较高,MAU水平也较高。     

尿微量白蛋白与2型糖尿病患者伴下肢血管病变的相关性分析

目的探讨2型糖尿病患者尿微量白蛋白水平与下肢血管病变的关系。方法收集96例2012年1月-6月在本院内分泌科住院的2型糖尿病患者,采用彩色多普勒超声诊断仪检测患者双侧股动脉、胭动脉、胫前动脉、胫后动脉。同时测尿微量白蛋白（mAlb）、空腹血糖（FBG）、糖化血红蛋白（HbA1c）、血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL—C）、高密度脂蛋白（HDL-C）、血肌酐（SCr）等,比较3组患者之间的差异。结果按超声检查结果分为3组：下肢动脉正常组30例（动脉内中膜厚度〈1．0mm）,有粥样斑块形成组38例,动脉狭窄或闭塞组28例。各组患者年龄、性别、体重指数、血压、血肌酐等差异无统计学意义,mA1b值各组间差异有统计学意义,尤其是动脉狭窄闭塞组与正常组间差异最显著。结论2型糖尿病患者尿微量白蛋白水平与下肢血管动脉硬化程度呈正相关,mA1b可预测2型糖尿病患者大血管病变的风险。     

Effect of atorvastatin on LDL oxidation and antioxidants in normocholesterolemic type 2 diabetic patients

BACKGROUND: Oxidative stress in diabetes increases lipid peroxidation, which stimulates the development of atherosclerosis. METHODS: We investigated in a 3-month placebo-controlled study with 19 normocholesterolemic type 2 diabetic patients whether treatment with 10-mg atorvastatin influenced antioxidants and reduced LDL oxidizability, assessed by in vitro production of conjugated dienes after copper-induced LDL oxidation. RESULTS: The lag phase, as a measure of the resistance of LDL to oxidation, did not change (62.8+/-8.2 respectively 59.6+/-9.7 min, p=n.s.), while conjugated dienes decreased (512+/-74 respectively 487+/-50 nmol, p=0.012). Plasma alpha-tocopherol and ubiquinol levels decreased, while their ratios to LDL cholesterol remained stable. CONCLUSIONS: Atorvastatin favourably influences some parameters of LDL oxidation. Whether this effect is clinically relevant remains to be determined.     

Predictors of diabetic renal lesions in type 2 diabetes associated with microalbuminuria

Not all type 2 diabetic patients with microalbuminuria show the same pattern of renal tissue injury, and heterogeneity in renal lesions has been reported. We determine clinical and laboratory findings that predict the presence of typical diabetic glomerulosclerosis in type 2 diabetic patients with microalbuminuria. Twenty-three type 2 diabetic patients with microalbuminuria who underwent renal biopsy were investigated. Two patterns of renal biopsy findings were defined as type D (typical diabetic glomerulosclerosis) and type A (atherosclerotic nephropathy without evidence of diabetic glomerulopathy). Thirteen patients (57%) were classified as type D, and 10 (43%) as type A. In stepwise multiple regression analysis, severity of diabetic retinopathy (P = 0.0006), relatively high urinary N-acetyl-beta-D-glucosaminidase activity (P = 0.0013), and relatively low serum creatinine concentration (P = 0.0303) significantly predicted type D findings as opposed to type A (R2 = 0.734, P < 0.001). Certain patient characteristics can predict the presence of typical diabetic glomerulosclerosis in type 2 diabetic patients with microalbuminuria.     

血浆致动脉粥样硬化指数与早期2型糖尿病肾病的相关性研究

目的探讨血浆致动脉粥样硬化指数与早期2型糖尿病肾病的相关性。方法 2型糖尿病患者1 139例以血浆致动脉粥样硬化指数0.06为切点分为非致动脉硬化表型组(N组)和致动脉硬化表型组,进而按照血浆致动脉粥样硬化指数四分位数将后一组再分为四组,比较5组患者一般情况和生化指标。结果合并早期肾病者的血浆致动脉粥样硬化指数值明显高于不合并肾病者(P<0.01),随血浆致动脉粥样硬化指数的逐渐升高,男性患者的比例、患者的BMI、腰臀比、舒张压、总胆固醇、甘油三酯、LDL-C、尿酸、空腹血糖、纤维蛋白原以及早期肾病的患病率逐渐升高,患者的年龄、病程、HDL-C逐渐下降,5组间有统计学意义(P<0.05);多因素Logistic回归分析表明,血浆致动脉粥样硬化指数是早期2型糖尿病肾病的独立危险因素(OR=2.854,95%CI 1.094⁷.442)。结论血浆致动脉粥样硬化指数升高是2型糖尿病患者合并早期2型糖尿病肾病独立的预测指标。     

Inflammation and coronary angiography in asymptomatic type 2 diabetic subjects

Objective. Coronary artery disease (CAD) is prevalent in patients with type 2 diabetes mellitus (T2DM) and because it is often asymptomatic and extensive in comparison with CAD in subjects without diabetes, it represents a diagnostic challenge. The objective of the study was to investigate the prevalence of CAD in asymptomatic T2DM patients utilizing angiography and to investigate its association with cardiovascular (CV) risk factors, the metabolic syndrome and markers of inflammation. Material and methods. Eighty‐two patients with T2DM without symptoms of CAD, and with ?1 CV risk factor (hypertension, dyslipidaemia, premature familial CAD, smoking or microalbuminuria) underwent a diagnostic stress test and coronary angiography irrespective of stress test results. Stenosis detected in the main coronary arteries ?50% of lumen diameter was categorized as one‐, two‐ or three‐vessel disease. Inflammatory markers were analysed in fasting samples. Results. Fifteen men and two women had significant CAD (21%) (1‐vessel disease, n = 10; 2‐ or 3‐vessel disease, n = 7). Patients with 2‐ or 3‐vessel disease were significantly older and had a longer duration of diabetes, but the prevalence of other traditional CV risk factors or the metabolic syndrome was similar among those with 1‐vessel and those with 2‐ or 3‐vessel disease. Sensitivity for CAD of the stress test was low (0.35). The mean level of the pro‐inflammatory marker interleukin‐6 was elevated in patients with 2‐ to 3‐vessel CAD as compared to patients with no or 1‐vessel CAD (p<0.05). Conclusions. Significant CAD was found in 21% of asymptomatic patients with T2DM with ?1 CV risk factor. Inflammatory markers may be helpful in identifying patients that are likely to have significant CAD, but larger studies are warranted.     

2型糖尿病合并高血压患者睡眠质量调查分析

目的了解2型糖尿病合并高血压患者睡眠质量相关因素。方法随机抽取本辖区内372例2型糖尿病患者运用阿森斯失眠量表(AIS)进行睡眠情况调查,运用匹兹堡睡眠质量指数(PSQI)和睡眠日志对56例存在睡眠障碍的患者进一步分析;对其中237例糖尿病合并高血压患者进行睡眠障碍危险因素分析。结果 2型糖尿病合并高血压患者发生睡眠障碍比例达62.6%,合并高血压组患者的匹兹堡睡眠质量指数(PSQI)总分高于无高血压组(P<0.05);合并高血压组患者每晚总睡眠时间小于6 h的比例明显高于无高血压组(P<0.05)。抑郁情绪和糖尿病自我效能差是糖尿病合并高血压患者睡眠障碍的危险因素。结论 2型糖尿病合并高血压患者睡眠障碍发生率高,睡眠障碍程度重,应加强患者抑郁情绪的有效干预和提高自我效能。     

Hemodynamic effects of acute hyperglycemia in type 2 diabetic patients

OBJECTIVE: The aim of the present study was to evaluate the hemodynamic effects of acute hyperglycemia in type 2 diabetic patients and to see whether these effects are related to changes in nitric oxide (NO) availability. RESEARCH DESIGN AND METHODS: Twenty newly diagnosed complication-free diet-treated type 2 diabetic patients participated in the study. All patients underwent 3 hyperglycemic glucose clamps in random order: 1) the control study was performed with plasma glucose clamped at 18 mmol/l for 2 h; 2) the octreotide study with plasma insulin blocked at basal levels during the clamp; and 3) the L-arginine study with L-arginine (1 g/min) infused during the last 30 min of the clamp. A group of 8 patients also underwent a glutathione infusion (600 mg as an intravenous bolus followed by 5 mg/min infusion) during the clamp. RESULTS: During hyperglycemia, there were significant increments of systolic (sBP) (from 115.5 +/- 9.1 to 120.3 +/- 8.2 mmHg, P < 0.01) and diastolic (dBP) (from 70.3 +/- 7.8 to 79.7 +/- 5.3 mmHg, P < 0.01) blood pressure, as well as heart rate (from 75.2 +/- 7.8 to 80.8 +/- 5.4 beats/min, P < 0.01) and plasma catecholamines (P < 0.05). Squatting ratios, a measure of the baroreflex activity, significantly deteriorated after hyperglycemia (P < 0.01). The infusion of octreotide, used to avoid the possible confounding influence of insulin, did not change the hemodynamic effects of hyperglycemia. Glutathione, a free radical scavenger, completely prevented the vascular effects of hyperglycemia. L-Arginine produced a fall in sBP and dBP to baseline values and normalized squatting ratios. CONCLUSIONS: Acute hyperglycemia in newly diagnosed type 2 diabetic patients causes significant hemodynamic changes that are independent of endogenous insulin and are prevented by glutatione and reversed by L-arginine, suggesting an interference with endogenous NO availability. These observations could help explain the adverse cardiovascular effects of hyperglycemic spikes.