α-硫辛酸对糖尿病周围神经病变氧化应激和内皮功能的影响

目的观察α-硫辛酸（ALA）对2型糖尿病患者周围神经病变（DPN）氧化应激和内皮功能的影响。方法30例DPN患者予ALA600mg／d静脉滴注14天。检测治疗前后氧化应激功能指标和血管细胞黏附分子（VCAM-1）、细胞间黏附分子（ICAM1）的水平。结果ALA可抑制氧化应激功能,降低ICAM-1的水平升高超氧化物歧化酶（SOD）活力,降低丙二醛含量,差异均有统计学意义,VCAM-1治疗前后差异无统计学意义。结论ALA可抑制DPN患者氧化应激功能及降低ICAM-1水平。     

The effect of alpha-lipoic acid on the neurovascular reflex arc in patients with diabetic neuropathy assessed by capillary microscopy.

Patients with diabetic polyneuropathy are known to have an impaired neurovascular reflex arc compared to healthy controls. This is seen in a delayed decrease in microcirculation of the ipsilateral hand after cooling of the contralateral hand. The aim of this pilot study was to investigate whether intravenous alpha-lipoic acid (ALA) (Thioctacid, Asta Medica) therapy might be able to improve this impaired neurovascular reflex arc in patients with diabetic neuropathy. In addition, clinical effects were evaluated with the aid of the neuropathy symptom score (NSS) and the neuropathy disability score (NDS). Ten patients with diabetes mellitus and polyneuropathy (5 females, 5 males, 2 smokers, 5 IDDM, 5 NIDDM, body mass index 26.1 +/- 1.0 kg/m2, age 58.3 +/- 9.5 years, diabetes duration 15.7 +/- 11.2 years, Hb A1c 6.8 +/- 0.3%) were investigated by nail-fold capillaroscopy after contralateral cooling before and after intravenous therapy with 600 mg alpha-lipoic acid per day over 3 weeks. Cardiac autonomic neuropathy was excluded by beat-to-beat variation analysis. Symptoms of diabetic neuropathy were evaluated before and after therapy with the aid of the NSS and NDS. Capillary blood cell velocity (CBV) of the hand was determined before, during, and for the following 30 min after cooling (3 min at 15 degrees C) of the contralateral hand. Blood pressure, heart rate, and local skin temperature were monitored at 2-min intervals. ALA therapy resulted in a significant improvement of the microcirculatory response to cooling, as seen by an immediate decrease in CBV of 12. 3% (P < 0.02 vs before treatment), which was absent before therapy. Blood pressure, heart rate, and local skin temperature were not different between investigations. There was a significant improvement of the NSS after therapy (5.4 +/- 1.1 vs 8.6 +/- 1.1 points, P < 0.01). These results demonstrate that intravenous therapy with ALA has a positive influence on the impaired neurovascular reflex arc in patients with diabetic neuropathy.     

The effect of alpha-lipoic acid on symptoms and skin blood flow in diabetic neuropathy.

AIMS: Multiple pathogenic pathways are involved in diabetic neuropathy and diverse treatments have been tried without success. The aim of this study was to assess the effect of alpha-lipoic acid on skin blood flow in patients with diabetic neuropathy. METHODS: We measured skin blood flow in 13 control subjects and 19 patients with diabetic neuropathy using the laser Doppler blood flow technique. Skin blood flow and the extent of skin blood flow changes were compared before and after diabetic patients received 600 mg/day alpha-lipoic acid intravenously for 14 days. RESULTS: Although no significant differences in absolute values of skin blood flow or in the extent of changes were noted, symptoms were reduced after alpha-lipoic acid treatment. CONCLUSIONS: This study suggests that alpha-lipoic acid, a potent antioxidant, improves symptoms of diabetic neuropathy. Larger studies are needed to determine whether improvements in skin blood flow also occur in patients with diabetic neuropathy.     

血尿酸与2型糖尿病患者周围神经病变的相关性研究

目的：探讨血清尿酸（SUA）水平与2型糖尿病（T2DM）患者糖尿病周围神经并发症（DPN）的关系。方法选取2011年3月至2013年3月在首都医科大学附属复兴医院内分泌科住院及门诊就诊的T2DM患者920例。采集血清进行生化指标[空腹血糖（FBG）,糖化血红蛋白（HbA1c）,总胆固醇（TC）,甘油三酯（TG）,低密度脂蛋白胆固醇（LDL-C）,高密度脂蛋白胆固醇（HDL-C）,SUA]检测,同时对入组患者是否患有DPN进行诊断并记录。SUA水平四分位法分为4个水平,logistic回归分析不同尿酸水平与DPN发病率的关系。结果 logistic回归分析结果显示SUA水平＞3.5mg/dl即第2个四分位后,SUA即为DPN的危险因素,且随着SUA水平的升高,其影响程度增加,OR值分别为2.95（2.02～8.76）,3.06（1.75～6.45）,4.15（0.84～6.74）,均P＜0.05。结论 SUA是DPN的一个危险因素,在DPN的临床治疗中除了降糖、降脂和降压之外,有效地降低SUA水平应该成为治疗中的一个重要环节。     

Relationship between peripheral diabetic neuropathy and microvascular reactivity in patients with type 1 and type 2 diabetes mellitus -- neuropathy and microcirculation in diabetes.

The aim of the study was to evaluate differences in the relationship between peripheral diabetic neuropathy and microvascular reactivity in type 1 and type 2 diabetic patients. Twenty-eight type 1 and 37 type 2 diabetic patients were included in the study. Control groups consisted of 18 and 25, age and body mass index matched healthy persons. The presence of peripheral neuropathy was estimated by vibration perception threshold higher than 20 V evaluated by biothesiometry. Microvascular reactivity was examined by laser doppler fluxmetry using postocclusive reactive hyperemia and thermal hyperemia. The following variables of vascular reactivity were examined: peak flow after occlusion as a difference between maximal and basal perfusion (PORH (max)), mean velocity increase during postocclusive hyperemia (PORH (max)/t (1)), peak flow during thermal hyperemia (TH (max)) and the mean velocity increase in the perfusion during thermal hyperemia (TH (max)/t (2)). These parameters are expressed in perfusion units (PU) or in perfusion units per second (PU . s (-1)). The microvascular reactivity in type 1 diabetic patients without evidence of peripheral neuropathy was comparable with that in healthy persons and it was significantly higher than in type 1 diabetic patients with peripheral neuropathy in all tested parameters (PORH (max): 64 [40; 81] PU vs. 24 [17; 40] PU, p < 0.001, PORH (max)/t (1): 5.41 [2.69; 8.18] PU/s vs. 1.21 [0.69; 2.5] PU/s, p < 0.001, TH (max): 105 [77; 156] PU vs. 56 [46; 85] PU, p < 0.001 and TH (max)/t (2): 2.48 [1.67; 3.33] PU/s vs. 0.87 [0.73; 1.06] PU/s, p < 0.001). On the contrary, no difference in the microvascular reactivity parameters was found between type 2 diabetic patients with and without neuropathy (PORH (max): 48 [30; 60] PU vs. 49 [36; 57] PU, NS, PORH (max)/t (1): 3.46 [2.15; 5.19] PU/s vs. 3.29 [2.45; 4.8] PU/s, NS, TH (max): 95 [78; 156] PU vs. 97 [73; 127] PU, NS and TH (max)/t (2): 1.45 [0.95; 2.84] PU/s vs. 1.37 [1.12; 1.95] PU/s, NS). In both these groups microvascular reactivity was comparable with that estimated in the age and BMI matched healthy persons. An inverse relationship was observed between microvascular reactivity and vibratory perception threshold in type 1 diabetic patients, but it was not true in type 2 diabetic patients. We suppose that the pathogenesis of neuropathy and impaired microvascular reactivity may be differently influenced by metabolic factors in type 1 and type 2 diabetic patients.     

葛根素注射液治疗糖尿病周围神经病变的疗效观察

目的 观察葛根素注射液治疗糖尿病周围神经病变（ＤＰＮ）的疗效。方法 采用葛根素注射液治疗ＤＰＮ６６例,同时与甲钴胺治疗的２２例作对照,观察葛根素注射液对ＤＰＮ患者肌电图,空腹血糖,糖化血红蛋白、血液流变学及红细胞山梨醇的影响。结果 治疗组显效率为５１．５１％,对照组为２２．７２％（Ｐ〈０．０１）,治疗组总有效率为８９．３９％,对照组为５８．１０％（Ｐ〈０．０５）,治疗组在治疗后,空腹血糖略有下降（     

Efficacy and safety of alpha-lipoic acid supplementation in the treatment of symptomatic diabetic neuropathy

PURPOSE: The purpose of this article is to review current evidence available for alpha-lipoic acid (ALA) and its ability to improve symptoms of peripheral diabetic neuropathy (PDN). METHODS: This article searched MEDLINE from 1966 to November 2005 to identify clinical trials that supplemented ALA to individuals with type 1 or type 2 diabetes and positive sensory symptoms of PDN. Clinical trials to be included in this review met specific criteria of randomization, double masking, and placebo-controlled design. RESULTS: The search results produced 5 clinical trials that met the prerequisites for this review. ALA appears to improve neuropathic symptoms and deficits when administered via parenteral supplementation over a 3-week period. Oral treatment with ALA appears to have more conflicting data whether it improves sensory symptoms or just neuropathic deficits alone. An oral regimen of ALA and optimal length of treatment remains unclear. Both parenteral and up to a 2-year time period of oral supplementation of ALA appears to be safe without affecting glycemic control. CONCLUSIONS: Based on these results, ALA should be considered as a treatment option for patients with PDN. When discussing supplementation with patients, it is important to discuss potential side effects; vitamin, mineral, and drug interactions; and current evidence available regarding efficacy.     

赖诺普利对糖尿病大鼠周围神经微循环的影响

目的 观察赖诺普利对糖尿病大鼠周围神经微循环的改善及对神经组织功能和结构的影响.方法 将25只约6周龄健康雄性Wistar大鼠以链脲佐菌素（STZ）尾静脉注射制备糖尿病大鼠模型,成模后按随机数字表法分为糖尿病组（n=8）和赖诺普利治疗组（n=8,20 mg· kg-1 ·d-1,8周）,8只健康大鼠作为正常对照.8周后,观察各组大鼠坐骨神经传导速度及超微结构的改变.采用化学比色法测定血浆一氧化氮（NO）,神经组织氧化应激指标超氧化物歧化酶（SOD）、丙二醛（MDA）水平,放射免疫法测定血浆前列环素（6-keto-PGF1 α）含量,酶联免疫吸附法（ELISA）测定血浆纤溶酶原激活物抑制物（PAI-1）、组织型纤溶酶原激活物（t-PA）水平,CD34免疫组化法测定坐骨神经内膜毛细血管密度.采用单因素方差分析进行多组间均数比较.结果 与正常对照组相比,糖尿病大鼠出现坐骨神经运动和感觉神经传导速度减慢（t=8.952、9.642,均P＜0.05）和超微结构异常,伴有血浆NO、6-keto-PGFlα、t-PA、SOD水平降低,PAI-1及MDA水平升高（t=3.535～8.054,均P＜0.05）.赖诺普利治疗组坐骨神经运动和感觉神经传导速度均较糖尿病组显著提高（t=6.774、7.058,均P＜0.05）,电镜显示赖诺普利治疗组坐骨神经轴突和髓鞘萎缩、变性及毛细血管狭窄、闭塞等病理损伤明显减轻.与糖尿病组相比,赖诺普利治疗组血浆NO、6-keto-PGF1 α、t-PA、SOD显著升高而PAI-1、MDA明显降低（t=2.611 ～6.544,均P＜0.05）,促进神经内膜血管新生（t=6.868,P＜0.05）.结论 赖诺普利可能通过改善微循环异常,增加周围神经血流灌注量,对早期糖尿病周围神经病变起保护作用.     

糖尿病周围神经病变患者足底压力变化

目的 了解2型糖尿病合并周围神经病变患者足底压力变化特点.方法 根据患者有无合并周围神经病变将2004年1月至2009年12月诊治的1103例2型糖尿病患者分为合并周围神经病变组（DPN组,n=301）和无周围神经病变组（DC组,n=802）.记录患者一般资料;测定血脂谱、空腹血糖和糖化血红蛋白水平及尿蛋白排泄率;用足底压力测量仪一步法测量两脚各5次动态足底压力,计算足底压力参数值.对研究数据采用独立样本t检验或Mann-Whitney U检验进行统计分析.结果 相比DC组,DPN组患者年龄大、腰臀围比值大、收缩压高、空腹血糖和糖化血红蛋白水平高、尿白蛋白排泄率高（均P＜0.05）.两组足底峰值压力差异无统计学意义（P＞0.05）;但DPN组接触时间延长[分别为（1484±412）和（1241±281）ms,t=-9.414,P＜0.05],压力-时间积分[分别为（333±115）和（278±89）kPa·s,t=-7.446,P＜0.05]和应力-时间积分[分别为（628±187）和（536±149）N·s,t=-7.707,P＜0.05]增加.与DC组相比,DPN组足跟[分别为（396±101）和（411±105）kPa,t=2.163,P＜0.05]和第2跖骨头[分别为（240±87）和（269±95）kPa,t=4.563,P＜0.05]、第3跖骨头[分别为（241±75）和（262±77）kPa,t=4.046,P＜0.05]峰值压力降低,但足弓[分别为（122±48）和（115±31）kPa,t=-2.487,P＜0.05]和第5跖骨头[分别为（218±116）和（195±99）kPa,t=-3.131,P＜0.05]及第3～5趾区域[分别为（108±50）和（98±46）kPa,t=-3.315,P＜0.01]峰值压力增高.而与DC组相比,DPN组足跟[分别为（228±100）和（189±67）kPa·s,t=-6.201,P＜0.05]、足弓[分别为（82±45）和（66±26）kPa·s,t=-6.151,P＜0.05]及前足底各个区域的压力-时间积分均明显增高.结论糖尿病周围神经病变患者足底压力分布异常、承受压力时间延长;两种因素共同作用致足底压力-时间积分增高,后者可致糖尿病足压力性溃疡.     

Ethnic differences in plantar pressures in diabetic patients with peripheral neuropathy

Aims To compare plantar foot pressures between Caucasian and Hispanic diabetic patients with peripheral neuropathy (PN) without a history of foot ulceration and between Caucasian and Hispanic non-diabetic individuals. Methods Forty-four Hispanic diabetic patients with PN (HDPN), 35 Caucasian diabetic patients with PN (CDPN), 41 non-diabetic Hispanic subjects and 33 non-diabetic Caucasian subjects participated. Total and regional peak plantar pressures (PPs) and pressure time integrals (PTIs) were assessed using the EMED-SF-4 plantar pressure system. Results Hispanic diabetic patients with PN had significantly lower peak PP than Caucasian diabetic patients with PN in the entire foot (552.4 ± 227.9 vs. 810.1 ± 274.6 kPa; P < 0.001), forefoot (464.1 ± 222.6 vs. 699.6 ± 323.1 kPa; P < 0.001), hindfoot (296.3.4 + 101.8 vs. 398.1 + 178.3 kPa; P < 0.01) and at the fifth metatarsal head (MTH5; 204.3 ± 143.2 vs. 388.2 ± 273.9 kPa; P < 0.001). The PTI in the entire foot, forefoot and MTH5 were also lower in HDPN than in CDPN. The ethnic differences between the diabetic groups with PN for the entire foot, forefoot and MTH5 remained significant after adjusting for the effect of age, gender, weight and duration of diabetes. There were no significant differences in peak PP and PTI among non-diabetic individuals, except for a lower peak PP at the MTH5 in Hispanic compared with Caucasian subjects. Conclusions Despite a well-known higher incidence of foot complications in diabetic Hispanic subjects, dynamic plantar pressures are lower in Hispanic diabetic patients with PN when compared with their Caucasian counterparts, suggesting that differences in other risk factors exist between these two ethnic groups.     

血管紧张素转换酶抑制剂对糖尿病大鼠周围神经病变的防治作用

目的研究血管紧张素转换酶抑制剂(ACEI)对精尿病大鼠周围神经病变的防治作用,并探讨其作用机制.方法链脲佐菌素(STZ)诱导糖尿病大鼠,预防及治疗性给药8周,观察赖诺普利(lisinopril)对坐骨神经传导速度及超微结构的影响;并测定神经组织超氧化物歧化酶(SOD)、丙二醛(MDA)、Na+-K+-ATPase活性及神经丝蛋白、髓鞘碱性蛋白(MBP)的表达、神经内膜毛细血管密度.结果赖诺普利预防或治疗可不同程度地改善坐骨神经的功能和结构;改善神经组织的氧化应激状态、提高Na+ -K+ -ATPase活性、增加神经结构蛋白的表达、促进血管新生.结论 ACEI足防治糖尿病周围神经病变的有效措施,其机制可能与改善神经组织缺血及相关代谢紊乱有关.     

针刺激痛点治疗糖尿病周围神经病变的临床疗效

目的 探讨针刺激痛点治疗糖尿病周围神经病变的临床疗效与安全性.方法 选取2018年9月至2020年1月在徐州医科大学附属医院疼痛科住院治疗的52例糖尿病周围神经病变(DPN)患者,采用随机数表法分为试验组和对照组.对照组给予口服降糖药物等基础治疗,试验组在此基础上行针刺激痛点治疗,观察并记录患者治疗前,治疗后1周、1个...     

α-硫辛酸对糖尿病周围神经病变的疗效

选择40例2型糖尿病并发糖尿病周围神经病变（DPN）患者分别静脉注射α-硫辛酸和甲钴胺连续2周，发现α-硫辛酸可以提高DPN患者神经传导速度，同时降低尿微量白蛋白、血浆内皮素和C反应蛋白，具有显著疗效，并且其疗效与甲钴胺相仿。     

Effects of oxygen inhalation on skin microcirculation in patients with peripheral arterial occlusive disease.

BACKGROUND. Oxygen administration is currently used in clinical medicine to improve peripheral oxygen delivery to tissues threatened by ischemia. However, conflicting results have been reported on the effects of oxygen in ischemic areas. This study was aimed at investigating the effects of 40% oxygen inhalation on the skin microcirculation in the feet of patients with peripheral arterial occlusive disease (PAOD). METHODS AND RESULTS. Transcutaneous oxygen tension (tc PO2) was measured on the dorsal skin of the foot, and the nailfold microcirculation was investigated by a combination of laser Doppler flowmetry (LDF) and dynamic capillaroscopy (CBV) in the great toes of 17 legs of 11 patients, with 13 legs of eight normal subjects as a control group. Inhalation of oxygen induced a significant decrease of both the total (delta LDF, -307%, p less than 0.02) and nutritional (delta CBV, -17%, p less 0.002) skin microcirculation in normal legs compared with baseline values. A similar response was observed in 10 legs of patients who showed a significant increase of the tc PO2 (greater than or equal to 10 mm Hg) (delta LDF, -14%, NS; delta CBV, -13%, p less than 0.005). By contrast, both the total (+21%, p less than 0.03) and nutritional (+52%, p less than 0.05) circulation significantly increased in the seven legs without significant tc PO2 increase. In addition, the flow motion, which was impaired in the patients, was significantly (p less than 0.05) improved by oxygen inhalation. CONCLUSIONS. Inhalation of 40% oxygen induces a vasoconstriction in the skin microcirculation of toes of the normal subjects and patients with moderate PAOD but induces an increase of the skin microcirculation in patients with severe PAOD.