An Investigation of Antibodies to Nerve Growth Factor in Diabetic Autonomic Neuropathy

Nerve growth factor (NGF) is required for development and maintenance of autonomic nervous function and is highly expressed in the iris. An association between sensory and autonomic diabetic neuropathy and NGF function has been postulated. In light of the evidence for an autoimmune component to the pathogenesis of autonomic neuropathy in Type 1 diabetes mellitus, an enzyme linked immunosorbent assay (ELISA) was established to investigate the presence of autoantibodies to mNGF in: 20 patients with long-standing Type 1 diabetes with abnormal autonomic function tests, of whom 14 had symptomatic autonomic neuropathy, 3 had an episode of iritis, and 6 had no autonomic symptoms; 9 age-matched patients with Type 1 diabetes and no complications; 10 healthy control subjects. Insulin antibodies by ELISA and autoantibodies to other endocrine targets were also measured. The specificity of anti-mNGF autoantibody ELISA was further confirmed by immunodepletion on mNGF-Sepharose 4B. No differences in antibody binding to mNGF were detected, between any of the patient groups and control subjects. There was no relationship between age, sex, and diabetes duration and mNGF binding. High levels of anti-mNGF autoantibodies were found in only one diabetic patient who had no evidence of neuropathy, raising the possibility that an autoimmune component to NGF might precede the development of autonomic dysfunction. It remains to be established whether autoantibodies to NGF play a role in diabetic autonomic neuropathy and prospective studies will be required to investigate whether the autoantibodies are a feature of evolving but not established neuropathy.     

Growth Factors and Diabetic Neuropathy

A variety of soluble growth factors influence the peripheral nervous system. Although of considerable importance during development and growth, they appear also to be implicated in tissue maintenance in adult life and, particularly, during nerve regeneration. In addition, cell-surface and extracellular connective tissue matrix molecules are intimately involved in regeneration. So far, the possible participation of such growth factors in the causation of diabetic neuropathy is only speculative, but there are indications that their use could be of value in treatment.     

Insulin-like Growth Factor-I and IGF-I Receptors in Diabetic Patients with Neuropathy

Since a number of animal studies have shown that Insulin-like growth I (IGF-I) stimulates nerve regeneration, the aim of our study was to evaluate the possible relationship between IGF-I and IGF-I receptors in diabetic patients with peripheral neuropathy. One hundred and four patients with Type 2 diabetes (57 with peripheral neuropathy and 47 non-neuropathic) were studied. Controls were 17 non-diabetic persons. After an overnight fast, blood was taken for IGF-I, IGF-I receptors, glucose, HbA₁, C-peptide, and insulin. The neuropathy study group had significantly lower levels of IGF-I:144.5 ng mI^-1 (57.5–363.0, 95% confidence limits) compared to controls: 186.2 ng mI^-1 (93.3–371.5), p<0.01, and to diabetic patients without neuropathy: 173.7 ng mI^-1 (83.1–363.0), p<0.01. The study group also had a lower number of IGF-I receptors per red cell: 22.9 times 10³ (13.08–38.01) vs control subjects: 28.1 times 10³ (18.62–42.65), p<0.01, and non-neuropathic diabetic patients: 26.3 times 10³ (16.59–41.68), p<0.01. In diabetic subjects there was a positive correlation (r = 0.20, p<0.05) between IGF-I and HbA₁, while in the neuropathy group there was a negative correlation between the score for nerve dysfunction with the IGF-I (r = -0.39, p<0.01) and with IGF-I receptors (r = -0.34, p<0.01). We conclude that in diabetic patients with peripheral neuropathy there are abnormalities of IGF-I and IGF-I receptors which may contribute to impaired neuronal regeneration.     

神经生长因子对糖尿病大鼠坐骨神经形态学的影响

目的 研究神经生长因子(NGF)对糖尿病大鼠周围神经病变的影响。方法 糖尿病大鼠造模后2周开始连续后肢肌注 NGF(800 U·kg~(-1)·d~(-1)),应用甲苯胺蓝染色及透射电镜观察大鼠坐骨神经的形态学变化。结果 糖尿病造模后2周电镜下坐骨神经即出现葱管样改变,且该病理改变随时间加重,6个月出现脱髓鞘。3个月及6个月NGF治疗组(NGF组)大鼠坐骨神经的神经纤维髓鞘及轴突面积较相应的糖尿病组(DM组)均增加,3个月NGF组及DM组坐骨神经纤维髓鞘面积分别为(47.48±11.84)μm~2和(44.86±12.28)μm~2(P<0.05);6个月分别为(57.76±10.33)μm~2和(46.34±11.57)μm~2(P<0.05)。3个月NGF组及DM组坐骨神经纤维的轴突面积分别为(22.86±9.59)μm~2和(19.86±7.78)μm~2(P<0.05);6个月分别为(23.90±7.18)μm~2和(20.29±6.67)μm(P<0.05)。6个月NGF组较3个月组髓鞘面积增加,并可减少坐骨神经纤维脱髓鞘。结论 早期、长期应用NGF可以有效改善糖尿病大鼠周围神经病变的形态。     

Autonomic and Peripheral Nerve Function in Early Diabetic Neuropathy

ABSTRACT. Sundkvist G, Lilja B, Rosén I, Agardh C-D (Departments of Internal Medicine and Clinical Physiology, Malmö General Hospital, and Departments of Clinical Neurophysiology and Internal Medicine, University Hospital, University of Lund, Lund, Sweden). Autonomic and peripheral nerve function in early diabetic neuropathy. Possible influence of a novel aldose reductase inhibitor on autonomic function. Acta Med Scand 1987; 221:445–53. Autonomic and peripheral nerve functions as well as the possible short-term effect of a novel aldose reductase inhibitor (ARI) on neuropathy were evaluated in 30 male type I diabetics (age 25–44 years, mean 34; duration of diabetes 10–20 years, mean 34) with neurographic signs of peripheral neuropathy (PN). Autonomic neuropathy (AN) was established by the heart rate reactions to deep breathing (E/I ratio = vagal function) and to tilt (acceleration index = sympathetic and vagal functions; the brake index = vagal function). Twenty-nine patients, 13 with AN, completed the study. Among neurographic variables, only sural nerve function tests correlated with autonomic functions. Patients with AN showed significantly lower mean sensory action potential amplitudes (SAPA) sural, indicating axonal losses, than patients without AN (3.58±0.79 μV vs. 7.34±1.12 μV; p<0.01). PN as measured by neurography did not improve during ARI treatment. On the other hand, vagal function (brake indices) improved (p<0.05) during ARI in AN patients.     

温针疗法治疗糖尿病周围神经病变临床疗效观察

目的探究应用温针疗法治疗糖尿病周围神经病变临床疗效。方法于2018年2月—2019年1月期间择取该院收治的68例糖尿病周围神经患者开展课题研究,将其随机划分为两组进行治疗并比较其临床疗效。调研组患者应用温针疗法,常规组患者注射弥可保治疗。结果调研组患者中共计有19例得到显效治疗,11例得到有效治疗,临床疗效优于常规组患者,组间差异有统计学意义(χ^2=9.827,P<0.05);调研组患者接受治疗后神经传导速度高于常规组患者,差异有统计学意义(t=9.852、9.958,P<0.05)。结论利用温针疗法治疗糖尿病周围神经病变疾病疗效好,可有效改善患者肢体神经传导,建议在临床中应用。     

神经生长因子改善实验性糖尿病大鼠的感觉神经功能

观察了链脲佐菌素糖尿病大鼠成模两个月后，投用神经生长因子（ＮＧＦ）对糖尿病神经病变的影响。结果显示，外源性注射ＮＧＦ１个月后，摇尾试验（一种鼠对热毒刺激的反应）热痛阈值明显恢复，坐骨神经的感觉神经传导速度有所改善。初步显示了ＮＧＦ对糖尿病感觉神经病变的治疗作用。     

依帕司他联合甲钴胺治疗糖尿病周围神经病变的疗效分析

目的 探讨依帕司他联合甲钴胺治疗糖尿病周围神经病变的临床疗效.方法 选择该科2018年9月—2020年9月收治的87例2型糖尿病周围神经病变患者,随机分为对照组(43例)和依帕司他组(44例).对照组采用甲钴胺治疗,依帕司他组增加依帕司他治疗,对比两组治疗前后神经病变改善情况,并监测氧化应激指标变化及用药安全性.结果 ...     

抗阻运动结合模块化营养指导对糖尿病周围神经病变患者神经传导功能的影响

目的 探讨抗阻运动结合模块化营养指导对糖尿病周围神经病变患者神经传导功能的影响.方法 选择2018年9月—2020年7月收治的86例糖尿病周围神经病变患者为研究对象,随机数字表法分为对照组与观察组,各43例,对照组接受常规护理,观察组在对照组基础上实施抗阻运动结合模块化营养指导,对两组血糖控制情况及神经传导功能、生活质...