丹参注射液对维持性血液透析患者胰岛素抵抗作用的临床研究

目的观察丹参注射液对维持性血液透析患者胰岛素抵抗的作用并探讨其机制。方法将60例存在胰岛素抵抗的血液透析患者随机分为两组,治疗组在血液透析中使用0．9％氯化钠100ml加丹参注射液20ml静滴,而对照组则使用氯化钠120ml静滴,疗程为6个月。检测治疗前、后胰岛素抵抗指数以及血脂、肝功能及脂联素水平,并将胰岛素抵抗指数与脂联素行相关分析,监测不良反应。结果两组治疗前指标及胰岛素抵抗指数无明显差异,治疗组在治疗后脂联素水平升高,血脂和胰岛素抵抗指数显著降低,而对照组无显著改变。两组患者治疗前、后肝功能无明显变化,未监测到明显不良反应,胰岛素抵抗指数与脂联素呈负相关。结论丹参注射液可提高脂联素表达水平,改善胰岛素抵抗。     

Relation between pulmonary function and inflammatory biomarkers in hemodialysis patients

The purpose of our study was to investigate the relationship between pulmonary function and serum levels of C-reactive protein (CRP), ferritin, albumin, and erythrocyte sedimentation rate, as inflammatory biomarkers, in hemodialysis patients. Ninety-eight patients, who were dialyzed at least for 3 months, were included in this study. Patients' blood samples were collected and pulmonary function tests, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF) were measured and expressed as the %predicted using appropriate normal values for the patients' sex, age, and height (%FVC, %FEV1, and %PEF), at the same time. The patients with CRP ≥ 10 μg/mL were significantly older and had lower values of %FEV1, %FVC and %PEF (p = 0.006, p = 0.001, and p = 0.016, respectively); whereas just %FEV1 (p = 0.025) and %FVC (p = 0.009) had significant differences between the patients with ferritin ≥ 100 μg/L and other patients. However, no other significant differences were found between inflammatory biomarkers and the pulmonary function tests. We concluded that inflammation has a close relation with pulmonary dysfunction in hemodialysis patients.     

Effects of N-3 PUFAs Supplementation on Insulin Resistance and Inflammatory Biomarkers in Hemodialysis Patients

Aims/Hypothesis. It was suggested that polyunsaturated n-3 fatty acids (n-3 PUFAs) could improve insulin sensitivity and have an anti-inflammatory effects in overall population. This study investigates a possible effect of n-3 PUFAs supplementation on the insulin sensitivity and some inflammatory markers; hence, patients with chronic renal failure (CRF) on maintenance hemodialysis (MHD) are presented with insulin resistance. Methods. This study explored the ratio between red blood cells (RBC) phospholipid long chain fatty acids (LC FAs) and components of metabolic syndrome (MeS) in 35 patients (mean age 54.50 ± 11.99 years) with CRF on MHD. Furthermore, the effects of omega-3 FA eight-week's supplementation (EPA+DHA, 2.4g/d) on the MeS features and inflammatory markers TNF-alpha, IL 6, and hsCRP were examined. Results. Supplementation increased EPA and DHA levels in RBCs (p = 0.009 for EPA and p = 0.002 for DHA). Total n-6 PUFAs: n-3 PUFAs ratio tended to be lower after supplementation (p = 0.31), but not significantly. Data revealed a significant decrease of saturated FAs (SFA) (p = 0.01) as well as total SFA: n-3 PUFAs ratio during the treatment (p = 0.04). The values of serum insulin and calculated IR index-IR HOMA were reduced after supplementation (p = 0.001 for both). There was a significant decrease in the levels of all inflammatory markers (p = 0.01 for TNF alpha, p = 0.001 for IL 6, p = 0.001 for hsCRP, and p = 0.01 for ferritin). In multivariate regression analysis, only the changes in n-6 PUFAs: n-3 PUFAs ratio independently contributed to 40% of the variance in IR HOMA. The impact of changes in PUFAs level in RBCs membrane phospholipid fatty acids on inflammation markers was also registered. The changes in n-6: n-3 PUFAs ratio independently contributed to 18% of the variance in TNF alpha. Conclusion. It was concluded that the EPA and DHA moderate dose administration in the patients with CRF on MHD had a beneficial effect on insulin resistance decrease. The anti-inflammatory effects of the supplemented PUFAs were also presented.     

Association of inflammatory biomarkers with metabolic syndrome in hemodialysis patients

The relative importance of inflammatory markers in relation with metabolic syndrome (MeS) in hemodialysis (HD) patients is uncertain. This study investigated the association between MeS and high-sensitive C-reactive protein (hsCRP), hallmark of inflammation, and other inflammatory-related biomarkers. The study included 153 patients who were dialyzed at least for the last 3?months. The serum level of hsCRP was assessed by high-sensitive Enzyme-linked immunosorbent assay (ELISA). MeS was defined using the modified National Cholesterol Education Program Adult Treatment Panel III (ATP-III). Ninety-one HD patients (59.5%) were diagnosed as having MeS. Lower level of high-density lipoprotein-cholesterol (HDL-C) was the most prevalent MeS component (85.6%). The serum level of hsCRP in these patients was significantly higher than that in HD patients without MeS (2.3?±?1.7 vs. 1.7?±?1.6?mg/dL, p?=?0.03). A significant linear increase in the hsCRP levels was found according to the number of MeS components (β?=?0.09, p?=?0.022). The study concluded that increasing inflammatory biomarkers, especially hsCRP, is associated with MeS in HD patients.     

丹参注射液对维持性血透患者胰岛素抵抗的作用

本研究观察丹参沣射液对维持性血液透析(MHD)患者胰岛素抵抗的作用及安全性.     

血液透析对尿毒症胰岛素拮抗和糖代谢的影响

目的研究血液透析对尿毒症胰岛素拮抗和糖代谢的影响。方法采用口服葡萄糖耐量试验（ＯＧＴＴ）和胰岛素释放试验（ＩＲＴ）方法，检测２２例血透（ＨＤ），２２例非透析（ＮＤ）尿毒症者和１２例正常者胰岛素敏感指数（ＩＳＩ）、机体糖利用率（Ｍ）、糖和胰岛素反应曲线下面积（ＡＵＣＧ和ＡＵＣＩＮＳ）。结果（１）ＨＤ组糖负荷后血糖、胰岛素水平及其ＡＵＣＧ、ＡＵＣＩＮＳ均显著低于ＮＤ组，但仍明显高于正常对照组；（２）ＨＤ组ＩＳＩ、Ｍ值显著高于ＮＤ组，但明显低于正常对照组，其胰岛素拮抗（ＩＲ）和糖耐量异常（ＩＧＴ）发生率均显著低于ＮＤ组：（３）胰岛素拮抗组血透时间显著短于非胰岛素拮抗组，透析时间与ＩＳＩ有正相关趋势；（４）ＨＤ组较ＮＤ组血ｐＨ值、血ＨＣＯ－３水平显著增高，但Ｎ－ＰＴＨ水平显著低下。结论ＨＤ可部分改善尿毒症胰岛素拮抗，高胰岛素血症和糖耐量异常。     

Effects of large dose vitamin E supplementation on anemia in hemodialysis patients

In order to clarify the effect of vitamin E (alpha-tocopherol) on anemia and the osmotic fragility of red blood cells (RBC) plasma and RBC levels of vitamin E were measured in 30 regular dialysis patients before and after oral supplementation of vitamin E, 600 mg daily for 30 days. Plasma levels of vitamin E were in the normal range (10.67 +/- 0.85, 9.73 +/- 0.77 microgram/ml) but RBC levels in packed red cells were significantly lower than healthy controls (0.57 +/- 0.05, 0.45 +/- 0.07 microgram/ml). Oral supplementation of vitamin E increased both plasma (20.37 +/- 1.61 micrograms/ml) and RBC vitamin E (1.56 +/- 0.11 micrograms/ml) in packed red cells, while in unsupplemented patients, vitamin E levels remained unchanged. In patients receiving vitamin E, mean osmolarities at the beginning and end of hemolysis decreased from 102.8 +/- 0.9 to 98.9 +/- 0.7 and 72.1 +/- 1.1 to 67.4 +/- 0.8 mosm/l, respectively. In addition, the hematocrit increased from 26.1 +/- 1.0 to 28.1 +/- 1.2%. These changes are statistically significant (less than 0.05). In conclusion, the oral supplementation of vitamin E could be of clinical benefit in correcting anemia in regular dialysis patients by reducing the fragility of RBCs.     

N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity

Reactive oxygen species formation and release of pro-inflammatory/pro-atherogenic cytokines, that is, interleukin 1-beta and tumor necrosis factor-alpha, need the activation of the arachidonic acid cascade via the enzyme 5-lipoxygenase (5-Lox). 5-Lox activity and expression are significantly increased in peripheral blood mononuclear cells (PBMCs) of end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). Diets enriched with n-3 polyunsaturated fatty acids (PUFAs) (omega-3) have been associated to a lower incidence of coronary heart disease (CHD) and a reduction in atherosclerotic lesions. Omega-3 may interfere with the arachidonic acid cascade by inhibiting 5-Lox. Lipid peroxidation, leukotriene B(4) (LTB(4)) production, 5-Lox activity and expression were investigated in PBMC isolated from ESRD patients under maintenance HD before and after a 3-month oral supplementation with omega-3 at a daily dose of 2700 mg of n-3 PUFAs at the average eicosapentaenoic acid/docosaesaenoic acid ratio of 1.2 and finally after a further 3-month washout with no omega-3 supplementation. PBMCs from non-uremic volunteers were also investigated for comparison to normal parameters. Administration of omega-3 reduced significantly lipid peroxidation (P < 0.0001), LTB(4) synthesis (P < 0.0001) and 5-Lox activity (P < 0.0001), with no effect on 5-Lox protein expression. After the 3-month washout, all parameters were comparable to those observed before treatment. Our results resemble those obtained after oral administration of vitamin E and are consistent with a reversible, dose-dependent inhibition of 5-Lox by omega-3. Upregulation of 5-Lox may also be related to the increased mitochondrial damage and apoptosis of PBMCs observed in ESRD patients compared to non-uremic controls. Omega-3 may thus protect PBMCs of ESRD patients against oxidative stress.     

Amelioration of hypertension and insulin resistance by 1,25-dihydroxycholecalciferol in hemodialysis patients

The effects of i.v. 1,25-dihydroxycholecalciferol (DHCC) on blood pressure and insulin sensitivity were studied in 7 patients on maintenance hemodialysis and compared with 7 healthy controls. Three days after discontinuing oral 1,25-DHCC, the dialysis patients were evaluated by glucose clamp studies to quantitate insulin sensitivity, with (+D) and without (–D) a prior single dose of i.v. 1,25-DHCC at 2g/m². Blood pressure was measured just before the glucose studies. During –D studies, the patients were hypertensive (mean arterial blood pressure 108±2 mmHg, controls 84±4 mmHg,P<0.02) and insulin resistant (insulin sensitivity index 7.5±0.4 mg/kg·min per U per ml, controls 14.2±0.7,P<0.01) i.v. 1,25-DHCC significantly reduced the mean arterial blood pressure (96±3 mmHg,P<0.05) and increased insulin sensivity (10.9±0.5 mg/kg·min per U per ml,P<0.02) in the dialysis patients. I. V. 1,25-DHCC did not change blood pressure and insulin sensitivity in the control subjects. During –D studies, serum concentrations of 1,25-DHCC were significantly lower in patients than controls (P<0.02). Serum 1,25-DHCC during the +D studies increased to supraphysiological levels in both patients and controls. Serum concentrations of intact parathyroid hormone, total and ionized calcium, magnesium, potassium, urea nitrogen and creatinine were not different between the +D and –D studies in either the dialysis patients or the controls. These results suggest that pharmacological doses of 1,25-DHCC may have therapeutic value in the treatment of hypertension and insulin resistance in dialysis patients.     

维持性血液透析患者微炎症和胰岛素抵抗与动脉粥样硬化的关系

目的 为了解维持性血液透析(MHD)患者微炎症状态、胰岛素抵抗及其与动脉粥样硬化(AS)的关系.方法 对101例MHD患者的临床资料进行分析,包括微炎症指标超敏C-反应蛋白、胰岛素抵抗HOMA-IR指数与动脉粥样硬化的关系.结果 动脉硬化组与无动脉硬化组比较,血浆白蛋白、前白蛋白和总胆固醇较低,P ＜0.01;而血糖、胰岛素、HOMA指数和C肽等则高于无动脉硬化组,P＜0.01.动脉硬化组有32.4％的患者有胰岛素抵抗,而无动脉硬化组胰岛素抵抗仅占1.7％,P＜0.01.Logistic回归分析发现,患者年龄、hsCRP和HOMA-IR增高是动脉粥样硬化的独立风险因素,而总胆固醇对动脉粥样硬化有保护作用.结论 MHD患者的年龄、微炎症状态及IR与AS密切相关,应作为降低MHD患者心脑血管并发症的治疗靶点.     

Impact of an exercise program on arterial stiffness and insulin resistance in hemodialysis patients

Cardiovascular disease remains the primary cause of mortality in patients who are maintained on hemodialysis. Arterial stiffness and insulin resistance are independent risk factors for cardiovascular mortality in this population. In healthy individuals, higher physical conditioning is associated with reduced arterial stiffness. Exercise reduces insulin resistance and glucose intolerance in sedentary, overweight individuals and diabetic patients. The purpose of this study was to determine the impact of an exercise program on arterial stiffness and insulin resistance in a group of patients on hemodialysis. The effect of exercise training on arterial stiffness and insulin resistance in 11 patients who were on chronic hemodialysis was evaluated. Exercise classes of 1-h duration were conducted twice weekly for 3 mo. Arterial stiffness was assessed using the radial artery pressure waveform analysis. Aerobic exercise improved arterial stiffness from 17 +/- 3 u at baseline to 12.2 +/- 3 u at the end of the intervention (P = 0.01). After 1 mo of detraining, arterial stiffness reverted to pre-exercise levels (17.3 +/- 3 u). Pulse pressure paralleled arterial stiffness changes, and the correlation between them was statistically significant (r = 0.725, P = 0.012). Insulin resistance was calculated using the homeostatic model assessment formula. Exercise at the intensity and duration used in our study had no impact on insulin resistance (P = 0.38). These findings suggest that 3 mo of aerobic exercise training improves arterial stiffness, an independent risk factor for cardiovascular mortality in patients who are on hemodialysis, and has no impact on insulin resistance. The beneficial effect on arterial stiffness dissipates within 1 mo of detraining. To obtain therapeutic benefits, an exercise program for patients who are maintained on hemodialysis should be designed to promote regular long term exercise, >3 h/wk.     

The effect of L-carnitine supplementation on lipid parameters, inflammatory and nutritional markers in maintenance hemodialysis patients

Protein energy malnutrition and inflammation are common and usually concurrent in maintenance hemodialysis (MHD) patients. Carnitine, a small molecule involved in fatty acid metabolism, is significantly decreased in long-term HD patients. L-Carnitine supplementation may have potential benefits in improving dialysis-related disorders. However, there are conflicting reports with regard to the beneficial effects of L-Carnitine supplementation. Hence, the present study was carried out to evaluate the effect of L-Carnitine supplementation on lipid parameters, apoproteins and inflammatory and nutritional markers in HD patients. A total of 35 patients with end-stage renal disease, on MHD for a period of 2 to 5 years were recruited into the study. The study group consisted of 20 patients who received Carnitine supplementation intravenously three times a week after each HD session, at 1 g/dose, while the control group consisted of 15 patients without supplementation with L-Carnitine. Highly sensitive C-reactive protein (hsCRP), total protein, albumin, lipid profile and apoprotein AI and B were determined at baseline and at the end of the study. A significant decrease in the hsCRP levels was observed in the Carnitine-supplemented group (P < 0.05). However, no significant change was observed in the lipid parameters and nutritional markers in the Carnitine-supplemented group. In conclusion, the present study demonstrates the significant benefit of L-Carnitine supplementation on inflammatory status in MHD patients as noted by marked decrease in hsCRP levels in comparison with the control group.     

Iron supplementation in adolescent hemodialysis patients

AIMS: Iron supplementation is necessary in children on hemodialysis, but the optimal protocol remains unknown. We studied the effects of changing our unit's protocol from oral iron with periodic doses of parenteral iron dextran to routine administration of parenteral sodium ferric gluconate on anemia and iron parameters. METHODS: We followed seven hemodialysis patients aged 15 20 years (mean 17 years). Hemoglobin, hematocrit, serum iron, transferrin saturation, ferritin, erythropoietin dose, total elemental iron dose and total iron cost for the six months prior to the protocol change were compared to the same variables during the six months following the change. RESULTS: There was no statistically significant difference between the doses of parenteral iron between the two protocols; however, the total dose of elemental iron administered in the oral iron plus iron dextran protocol was greater than in the sodium ferric gluconate protocol (19.6+/-13.1 (mean+/-SD) mg/kg/week versus 1.1+/-0.3 mg/kg/week; p = 0.03). Both protocols had equivalent efficacy with respect to hemoglobin, ferritin and other measures of iron stores. On the other hand, the costs of sodium ferric gluconate were significantly higher than those of oral iron plus intermittent iron dextran (157.75+/-45.94 $/patient/month versus 52.08+/-49.88 $/patient/month; p = 0.01). CONCLUSIONS: Routine administration of sodium ferric gluconate is equivalent if not superior to use of oral iron plus iron dextran for maintenance of iron stores in adolescents on hemodialysis, but more expensive.     

Nutritional supplementation in adult patients on hemodialysis.

At the beginning of the 1980s, nutritional status appeared as a key element of quality of life, health care requirements, and survival during chronic renal failure. In patients on dialysis, malnutrition is a major determinant of survival, and its management appears to be a key element in terms of outcome. Recommendations for the nutritional management of patients on hemodialysis have been elaborated by the National Kidney Foundation (NKF) and the European Society of Parenteral and Enteral Nutrition (ESPEN).     

血液透析患者颈总动脉僵硬度与胰岛素抵抗的关系

目的 探讨维持性血液透析患者颈总动脉僵硬度与胰岛素抵抗的关系。 方法 选取80例非糖尿病、病情稳定的血液透析患者为研究对象。采用超声血管壁跟踪系统（Echo-tracking）在血液透析结束后1 h测定颈总动脉硬化参数β作为评价大动脉僵硬度的指标。胰岛素抵抗用内环境稳定模型评估胰岛素抵抗法（HOMA-IR）进行评价。常规检测血红蛋白、白蛋白、总胆固醇、高密度脂蛋白、低密度脂蛋白、三酰甘油、脂蛋白(a)、载脂蛋白A1、载脂蛋白B、C反应蛋白、钙、磷、肌酐。用独立样本t检验、Pearson及多元逐步回归法分析各参数关系。 结果 既往有心血管病史者颈总动脉硬化参数β大于无心血管病史者（11.41±4.13比9.75±3.63，P < 0.05）。Pearson相关分析显示，颈总动脉硬化参数β与HOMA-IR（r = 0.321，P < 0.01、年龄（r = 0.376，P < 0.01）、脉压（r = 0.267，P < 0.05）、透析龄（r = 0.219，P < 0.05）呈正相关。多元逐步回归结果显示，HOMA-IR（β = 0.228，P < 0.05）、年龄（β = 0.308，P < 0.01）是颈总动脉硬化参数β增加的独立危险因素。 结论 在血液透析患者，胰岛素抵抗可能通过参与大动脉僵硬的发生，导致心血管疾病发病率和病死率增加。     

Effects of interval training on inflammatory biomarkers in patients with ischemic heart failure

Objectives. Exercise training has been proposed to have anti-inflammatory effects. We examined whether aerobic interval training (AIT) can attenuate the inflammatory response in ischemic heart failure (HF) as measured by serum biomarkers representing a broad spectrum of activated inflammatory pathways. Design. We conducted a controlled prospective trial recruiting 30 patients (19 in the AIT group and 11 in the control group) with ischemic HF and an implantable cardioverter defibrillator (ICD). This study is a sub study of the previously reported “Aerobic interval training in patients with heart failure and an ICD” (Eur J Prev Cardiol. 22 March 2015; 22:296–303). Patients in the AIT group exercised for 12-weeks completing a total of 36 AIT sessions. We analyzed serum levels of C-reactive protein, pentraxin-3, osteoprotegerin, brain natriuretic peptide, neopterin, and soluble tumor necrois factor type 1 and 2, all known to predict an adverse outcome in HF, at baseline and following the 12-week AIT intervention. Results. The AIT group significantly increased peak oxygen uptake and improved endothelial function compared to the sedentary control group. No statistically significant changes in serum levels of the biomarkers were detected from baseline following the AIT intervention and, there were no significant differences in changes of these mediators between the AIT and the control group. Conclusions. A 12-week AIT intervention, although improving exercise capacity and endothelial function, did not attenuate serum inflammatory biomarkers in stable ischemic HF patients with an ICD on optimal medical therapy.     

Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic review

There are many causes for carnitine depletion during maintenance hemodialysis. Supplementation with L-carnitine in animals has been associated with improvement in some abnormalities also present in chronic renal failure. However, it is still controversial whether restoring plasma or tissue carnitine will correct clinical or biologic symptoms observed in maintenance hemodialysis. A systematic review is here performed to determine the effects of L-carnitine in maintenance hemodialysis patients. Eighty-three prospective trials were identified from 1978 to 1999 in which L-carnitine was randomly allocated in 21 trials. Change in serum triglycerides, cholesterol fractions, hemoglobin levels, erythropoietin dose, and other symptoms (muscle function, exercise capacity, and quality of life) were examined. A total of 482 patients in 18 trials were considered for analysis. There was no effect of L-carnitine on triglycerides, total cholesterol, or any of its fractions. Before the erythropoietin (EPO) era, L-carnitine treatment was associated with improved hemoglobin (P < 0.01) and with a decreased EPO dose (P < 0.01) and improved resistance to EPO when patients routinely received EPO. Muscle function, exercise capacity, and quality of life could not be reliably assessed because of the noncombinable nature of end points and the limited number of trials. In conclusion, L-carnitine cannot be recommended for treating the dyslipidemia of maintenance hemodialysis patients. By contrast, this review suggests a promising effect of L-carnitine on anemia management. The route of L-carnitine administration should be evaluated because there is no evidence as to the most efficient method of administration in maintenance hemodialysis.     

Effects of vitamin supplementation on microcirculatory disturbance in hemodialysis patients without peripheral arterial disease

AIMS: Dysfunctional endothelium caused by oxidative stress is thought to play a role in pathogenesis of a variety of conditions including atherosclerosis. We investigated whether a microcirculatory disturbance in hemodialysis (HD) patients was associated with increased oxidative stress and endothelial injury. PATIENTS AND METHODS: Transcutaneous oxygen tension (TcPO2) on the dorsum of the foot at rest was measured as a marker of microcirculation in 33 patients undergoing HD without clinical manifestations of peripheral arterial disease and 20 healthy controls. Furthermore, in order to examine whether TcPO2 was affected by antioxidants, oral supplementation with a combination of vitamin C (200 mg daily) and vitamin E (600 mg daily) was administered for 6 months to 8 patients with microcirculatory disturbance (TcPO2 values of 50 mmHg or less). Serum biochemical parameters including vitamins were also measured. RESULTS: Mean TcPO2 value was significantly lower in HD patients than in control subjects (47.9 +/- 13.5 mmHg versus 62.4 +/- 11.9 mmHg, p < 0.001). After vitamin supplementation, TcPO2 values remarkably increased (40.6 +/- 10.0 mmHg versus 57.4 +/- 6.5 mmHg, p < 0.005). Serum vitamin C and vitamin E levels increased significantly as well, while serum levels of thrombomodulin, a marker of endothelial injury, and thiobarbituric acid reactants, a marker of lipid peroxidation, were significantly decreased in comparison with those before supplementation. CONCLUSIONS: Our results suggest that the microcirculatory disturbance in HD patients seems to be associated with endothelial damage caused by oxidative stress. Combined supplementation with vitamin C and vitamin E may be of clinical benefit in improving the cutaneous microcirculation by reducing oxidative stress.