Preventing foot ulceration and amputation by decompressing peripheral nerves in patients with diabetic neuropathy

Diabetic neuropathy occurs in a stocking and glove distribution, consistent with a systemic metabolic disease. As a result, it is commonly believed that no surgical options are available for this debilitating condition. The classic medical approach to the treatment of diabetic neuropathy consists of attempts to achieve a euglycemic state, obtain regular podiatric care of the feet, inspect the feet for the presence of deformities or ulcers, and help achieve pain control through the use of medication. Unfortunately, all too often this approach is not successful in relieving the patient's pain, and the loss of sensation provides the basis for deformity, ulceration, infection, and amputation. However, scientific and clinical research data support the statement that "today it is possible to restore sensation and relieve pain in 80% of patients with symptoms of diabetic neuropathy by decompression of multiple peripheral nerves." Furthermore, long-term follow-up has shown that no one who has had sensation restored with this procedure has developed an ulcer. These findings change the natural sequelae of diabetic neuropathy.     

Psychological variables associated with foot function and foot pain in patients with plantar heel pain

It is widely accepted that psychological variables are associated with self-reported pain and self-reported physical function in patients with musculoskeletal pain. However, the relationship between psychological variables and foot pain and foot function has not been evaluated in people with plantar heel pain. Eighty-four participants with plantar heel pain completed the Depression, Anxiety and Stress Scale short version (DASS-21) and Foot Health Status Questionnaire. Using a hierarchical regression analysis, a baseline model with age, sex and BMI explained 10 % of the variability in foot function. The addition of depression and stress in separate models explained an additional 7.3 % and 8.1 % of foot function scores, respectively. In the respective models, depression was a significant predictor (β?=??0.28; p?=?0.009) as was stress (β?=??0.29; p?=?0.006). Females drove the effect between stress and foot function (β?=??0.50; p?=?0.001) and depression and foot function (β?=??0.53; p?<?0.001). In regression models for foot pain, depression, anxiety and stress did not contribute significantly to pain scores. When the data was stratified by sex, stress (β?=??0.36; p?=?0.024) and depression (β?=??0.41; p?=?0.013) were significantly associated with foot pain in females but not in males. For participants with plantar heel pain, stress and depression scores were significantly associated with foot function but not foot pain. When the data was stratified by sex, stress and depression were significant predictors of foot pain and function in females.     

Pathogenesis of pain in peripheral diabetic neuropathy

Recent advances in understanding the pain associated with diabetic neuropathy are likely to provide significant mechanistic insights and offer better therapies. In clinical research, new tools for measuring neuropathic pain and validation of histologic and other biomarkers will provide the foundation for research advances, and new clinical trial designs will allow better discrimination of beneficial treatments and may reveal underlying pathogenic mechanisms. Ongoing refinement of relevant animal models and assays to more accurately reflect the clinical condition will improve evaluation of novel pharmacologic approaches while dissecting peripheral versus central effects of diabetes on pain pathways will provide a more complete picture of the pathophysiologic mechanisms. Such multidisciplinary work may soon allow physicians to offer improved therapeutic options to patients suffering this distressing condition.     

糖尿病足部汗腺分泌功能与周围神经病变及周围血管病变的关系

目的 研究2型糖尿病(T2DM)患者足部汗腺与周围神经病变及周围血管病变的关系.方法 分别采用血管彩色B超和欧米诺汗印法(新型诊断膏贴,Neumpad)对98例T2DM患者进行泌汗神经功能检测及周围血管检测,计算欧米诺汗印法左右足开始及完全变色时间.结果 糖尿病周围血管病变组左足及右足欧米诺开始变色时间分别为(3.7±2.66)min,(3.61 ±2.56) min,左足及右足欧米诺完全变色时间分别为:(22.07±9.97)min,(20.94±10.71)min;显著高于糖尿病无周围血管病变组(P＜0.05).结论 糖尿病合并周围血管病变患者足部泌汗功能差.     

糖尿病周围神经病变和血管病变对糖尿病足溃疡的相互作用及相关性探讨

目的 探讨糖尿病足溃疡（DFU）发生的危险因素,分析糖尿病周围神经病变（DPN）和糖尿病血管病变（PAD）与DFU的相互作用.方法 选取T2DM患者278例,按其是否合并DFU分成糖尿病足溃疡组（DFU,102例）和糖尿病非足溃疡组（NDFU,176例）,回顾性分析两组生化特征和并发症情况.采用Logistic回归分析DFU发生的危险因素,并通过相对超额危险度比（RERI）,归因比（AP）和相互作用指数（S）评价DPN与PAD的相加相互作用.结果 与NDFU组比较,DFU组HbA1c和纤维蛋白原（FIB）水平,DR、DPN和PAD发生率均升高,血红蛋白（Hb）、血白蛋白（Alb）、TC和LDL-C降低（P＜0.05）.Logistic回归分析显示,DFU相关影响因素有：HbA1 c、DPN、PAD、Hb、Alb和FIB（OR分别为1.41、3.66、3.00、0.98、0.79和2.51）.DPN和PAD对DFU的相加相互作用指标RERI、AP和S分别为3.45（95％CI：1.22～8.56）、0.29（95％CI：0.02～0.58）和1.45（95％CI：1.03～4.96）.结论 血糖控制欠佳、合并DPN和PAD、营养不良及FIB代谢失衡是DFU发生的主要危险因素.DPN和PAD对DFU存在相加相互作用,同时患有DPN和PAD可增加DFU的患病风险.     

Prevalence and risk factors for diabetic peripheral neuropathy,neuropathic pain and foot ulceration in the Arabian Gulf region

Aims/IntroductionThis study determined the prevalence and risk factors for diabetic peripheral neuropathy (DPN), painful DPN and diabetic foot ulceration (DFU) in patients with type 2 diabetes in secondary healthcare in Qatar, Kuwait and the Kingdom of Saudi Arabia.Materials and MethodsAdults aged 18–85 years with type 2 diabetes were randomly enrolled from secondary healthcare, and underwent clinical and metabolic assessment. DPN was evaluated using vibration perception threshold and neuropathic symptoms and painful Diabetic Peripheral Neuropathy was evaluated using the Douleur Neuropathique 4 questionnaire.ResultsA total of 3,021 individuals were recruited between June 2017 and May 2019. The prevalence of DPN was 33.3%, of whom 52.2% were at risk of DFU and 53.6% were undiagnosed. The prevalence of painful DPN was 43.3%, of whom 54.3% were undiagnosed. DFU was present in 2.9%. The adjusted odds ratios for DPN and painful DPN were higher with increasing diabetes duration, obesity, poor glycemic control and hyperlipidemia, and lower with greater physical activity. The adjusted odds ratio for DFU was higher with the presence of DPN, severe loss of vibration perception, hypertension and vitamin D deficiency.ConclusionsThis is the largest study to date from the Middle East showing a high prevalence of undiagnosed DPN, painful DPN and those at risk of DFU in patients with type 2 diabetes, and identifies their respective risk factors.     

The potential of transdermal nitric oxide treatment for diabetic peripheral neuropathy and diabetic foot ulcers

The Center for Disease Control (CDC) estimates that 29 million Americans have diabetes, and 70% of diabetic patients develop diabetic peripheral neuropathy [1,2]. Up to 27% of the direct medical cost of diabetes may be attributed to DPN [3]. A 2013 article from the American Diabetes Association reported a $176 billion direct medical cost of diabetes in 2012 [4]. DPN patients often suffer from shooting and burning pain in their distal limbs and a severe loss of sensation. Diabetic foot ulcers, infections, and amputations may follow. Currently available treatments: tricyclic antidepressants, anticonvulsants such as gabapentin and pregabalin, serotonin and norepinephrine reuptake inhibitor, duloxetine, topical 5% lidocaine (applied to the most painful area) can manage painful symptoms but do not address the underlying pathologies of DPN and diabetic wound ulcers. A combination of pain-reducing medications can provide relief when individual medications fail, and opioids such as tramadol and oxycodone may be administered with these medications to reduce pain [5]. Due to the prevalence of diabetes, DPN, and diabetic foot ulcers, and because of the lack of available effective treatments to directly address the pathology contributing to these conditions, novel treatments are being sought. Our hypothesis is that a deficiency of nitric oxide synthase in diabetic patients leads to a lack of vascularization of the peripheral nerves, which causes DPN; and this could be treated with vasodilators such as nitric oxide. In this paper, the mechanisms of DPN are reviewed and analyzed to elucidate the potential of a transdermal nitric oxide application for the treatment of DPN and diabetic wound ulcers by increasing vasodilation.     

Carfilzomib is an effective upfront treatment in AL amyloidosis patients with peripheral and autonomic neuropathy

Bortezomib is standard treatment in AL amyloidosis (AL), but is contraindicated in patients with significant neuropathy. Carfilzomib, a second-generation proteosomal inhibitor, results in a lower incidence of neuropathy than bortezomib, but data in AL is scant. We report a cohort of five AL patients treated with upfront carfilzomib. All had cardiac, peripheral and autonomic neuropathy at presentation. All achieved at least a very good partial haematological response. There was no worsening in cardiac function, peripheral or autonomic neuropathy. Carfilzomib is an effective upfront treatment option in AL patients with peripheral and/or autonomic neuropathy (without severe cardiac or renal involvement).     

Ambulatory blood pressure reduction after rosiglitazone treatment in patients with type 2 diabetes and hypertension correlates with insulin sensitivity increase

BACKGROUND: Within the metabolic syndrome, insulin resistance and compensatory hyperinsulinemia are associated with blood pressure (BP) elevation through various potential mechanisms. Thiazolidinediones are antihyperglycemic agents that decrease insulin resistance. OBJECTIVE: To determine the effect of the thiazolidinedione rosiglitazone on BP and insulin resistance in patients with type 2 diabetes and hypertension. METHODS: In 20 subjects (nine men and 11 women) with type 2 diabetes but with a poor glycemic control, and with poorly controlled or newly diagnosed hypertension, rosiglitazone 4 mg daily was added-on therapy for 26 weeks. At baseline and at the end of the treatment period patients underwent ambulatory blood pressure monitoring, a hyperinsulinemic euglycemic clamp, and blood tests for glucose, insulin, HbA1c, lipids, and routine laboratory parameters. RESULTS: Insulin sensitivity estimated with the clamp significantly increased (Mbw/I index changed from 33.9 +/- 2.6 to 41.9 +/- 3.2 micromol/min per kg per nmol/l, P < 0.001) and the HOMA-IR index significantly decreased (6.34 +/- 0.39 versus 4.40 +/- 0.33, P < 0.001) during rosiglitazone treatment. Ambulatory BP presented small but significant reductions for the total 24-h period (135.3 +/- 1.8 versus 129.9 +/- 1.7 mmHg, P < 0.001 for systolic BP and 76.0 +/- 1.6 versus 71.9 +/- 1.6 mmHg, P < 0.001 for diastolic BP), daytime and night-time. The changes in systolic and diastolic BP correlated with the change in insulin sensitivity (r = -0.78, P < 0.01 and r = -0.68, P < 0.01, respectively). There were also significant reductions in fasting plasma glucose (9.39 +/- 0.41 versus 7.55 +/- 0.31 mmol/l, P < 0.001), insulin (94.0 +/- 0.41 versus 79.5 +/- 5.6 pmol/l, P < 0.01) and HbA1c (8.15 +/- 0.24 versus 7.24 +/- 0.19%, P < 0.001). CONCLUSIONS: Treatment of type 2 diabetic hypertensive patients with rosiglitazone significantly increased insulin sensitivity and lowered ambulatory BP. These changes were strongly correlated. Thiazolidinediones may thus possess a BP-lowering effect beyond their antihyperglycemic properties.     

糖尿病足感觉性神经病变的评估与治疗

糖尿病足是糖尿病的严重并发症之一,糖尿病患者中有25%可能会患有糖尿病足。研究表明,糖尿病神经病变是糖尿病足发病的重要因素之一,约85%糖尿病足的发病与神经病变相关,而糖尿病神经病变通常累及感觉性神经纤维。因而更好地评估和治疗糖尿病足感觉性神经病变至关重要。本综述对糖尿病足感觉性神经病变的评估和治疗方法进行总结,希望能够对临床工作提供参考。     

Autoimmune reactions in patients with M-component and peripheral neuropathy.

A study of 17 patients with autoimmune axonal or demyelinating peripheral neuropathy in combination with M-component is described. The M-component was associated with MGUS (monoclonal gammopathy of undetermined significance) in 12 patients, CLL in one patient, WaldenstrÖm's disease in one patient, and myeloma in three patients. Immunohistological examination with direct and indirect fluorescence showed binding of antibodies to nerve structures of the same class and light chain as seen in the M-component. In five cases of IgM M-component, the demyelinating neuropathy was caused by binding of the IgM M-protein and complement C3b to myelin-associated glycoproteins (MAG). In 12 cases with axonal neuropathy, binding of IgG to the connective tissue of the peri- and endoneurium was found in 50% of cases, IgM in five cases, and IgD in one case. None of the patients had central nervous system (CNS) symptoms. The clinical and therapeutic difficulties are discussed; only two patients with an acute course responded to immunosuppression. A marked co-expression of other autoimmune phenomena is interpreted in the light of cross-reactions between the autoantibody and similar tissue autoantigens.     

糖尿病周围神经病变与足型及足底压力的关系

目的分析糖尿病周围神经病变与糖尿病患者足型及静态足底压力的关系。方法2007年8月20日至2008年10月14日从华西医院内分泌科门诊及住院患者中整群抽取540例糖尿病患者（糖尿病组）,其中男227例,女313例,平均年龄（59±12）岁,体质指数（24±4）kg／m^2;另从成都市武侯区纳入年龄、性别、体质指数匹配的健康者231名（健康对照组）,其中男84名,女147名,平均年龄（64±11）岁,体质指数（23±4）kg／m^2。由专人使用密西根神经病变筛查量表（MNSI量表）对糖尿病组患者进行周围神经病变评估。使用足底图像扫描仪及足底压力测量仪测定研究对象足型、足底各部位静态相对压力峰值。采用t检验或卡方检验进行数据统计。结果2组参试者足底静态平均压力峰值（36±21VS36±22,t=-0．544,P=0．587）及足底各部位静态压力峰值无明显差异。糖尿病患者据MNSI评分分成A组（MNSI评分0～4分）、B组（MNSI评分4．5—6．5分）、C组（MNSI评分7分以上）,3组人群体质量及体质指数与健康对照组无差异。3组人群静态足底平均压力峰值与健康对照组比较无明显差异（A组为36±20,B组为35±20,C组为35±20,健康对照组为36±22）。各组足底各部位静态相对压力峰值与健康对照组比较差异亦无统计学意义（均P〉0．05）。糖尿病组锤状趾的发生率明显高于健康对照组[8．7％（47／540）VS4．3％（10／231）,X^2=3．966,P=0．029]。糖尿病组锤状趾和扁平足患者MNSI评分[（6．2±2．0）分VS（5．4±1．2）分,t=2．145,P=0．032;（6．6±2．1）分VS（5．4±1．2）分,t=2．339,P=0．02]高于糖尿病患者。结论MNSI评分不能预测糖尿病患者足底静态压力的变化;糖尿病周围神经病变是足部畸形发生的危险因素;伴足底压力升高或足部畸形的糖尿病周围神经病变患者是糖尿病足的高危人群。     

Spinal accessory neuropathy in patients with chronic neck pain

AIM: To assess the presence of spinal accessory neuropathy in patients with chronic neck pain. METHODS: Patients with pain either regional or focal in the neck or shoulders for at least 6 mo (chronic neck pain) were recruited randomly from the Rheumatology and Rehabilitation Outpatient Clinic at the Faculty of Medicine-Suez Canal University. Two groups were compared: 30 patients with chronic neck pain with mean age (36.97 ± 12.45 years) and 10 apparently healthy controls. Trapezius muscle examination including inspection and range of motion both active and passive was performed. A full clinical neurological examination was carried out to exclude peripheral neuropathy and motor neuron disease. According to the subject’s type of work, cases were categorized into labor-intensive and non-labor intensive tasks. A nerve conduction study (NCS) was performed on spinal accessory nerves at both sides for all patients and controls. Parameters including latencies and amplitudes of compound motor action potential (CMAP) were compared with the chronicity of neck pain using the neck disability score. This cross sectional study was carried in the Rheumatology and Rehabilitation Department, at Suez Canal University Hospital, Ismailia, Egypt. RESULTS: Physical examination revealed that 80% of cases had spinal trapezius muscle spasm. Restricted neck motion was present in 16.6% of cases. No one suffered from muscle wasting or weakness. Pain was bilateral in 18 patients (60%), localized to the right side in six patients (20%) and localized to the left side in six patients (20%). The causes of neck pain in the patients studied were nonspecific, due to physical stresses, cervical spondylosis and mild cervical disc herniation. Mean disease duration in patients with labor-intensive tasks was (3.9 ± 2.1 years), which was longer than that in patients with non-labor intensive tasks (3.1 ± 1.9 years); however, this difference was statistically insignificant. Spinal accessory NCSs were performed while subjects were in sitting positions and relaxed with naturally suspended arms to minimize muscular movement. The results of electrophysiological studies revealed that mean right and left latencies of the spinal accessory nerve were 2.96 ± 0.69 ms, 2.98 ± 0.61 ms in the patient group and 2.44 ± 0.38 ms, 2.33 ± 0.36 ms in control group respectively. These differences were statistically significant with P = 0.028 and 0.006 respectively. Spinal accessory NCS showed normal CMAP amplitude in both patients and controls. Comparing the results of the neck disability index (NDI) to different characteristics in patients with chronic neck pain, showed that patients with labor-intensive work had a higher NDI score mean (34.7 ± 9.5) compared to those with non-labor-intensive work, with significant statistical difference (P = 0.011). In addition, mean NDI scores were higher in males, and patients aged over 40 years and this difference was statistically significant (P = 0.007 and P = 0.009 respectively). Correlation studies between right and left spinal accessory nerve latencies and disability percent calculated using the NDI revealed a positive correlation. Moreover, there was a positive correlation between age and disability percent. CONCLUSION: This study demonstrates electrophysiological evidence of demyelination in a significant proportion of patients with chronic cervical pain.     

Plantar sensitivity, foot loading and walking pain in rheumatoid arthritis

OBJECTIVE: The aim of the present study was to investigate the tactile sensitivity of the plantar surface in rheumatoid feet and its relationship to walking pain and plantar foot loading characteristics. METHODS: In 25 patients with rheumatoid arthritis (RA) and 21 healthy controls, Semmes-Weinstein monofilaments were used to assess tactile sensitivity in six foot regions. Walking pain was examined clinically. Pedography was used to analyse foot loading parameters during barefoot walking. RESULTS: In RA patients, plantar sensitivity was significantly decreased under all foot regions examined compared with the control group (P<0.05). A loss of protective sensation was found in a total of 10 regions in seven patients but not in the control group. In the RA patients, foot loading was reduced in the hindfoot (P<0.05) but was slightly increased in the forefoot (not significant). Average walking pain was 3.8 +/- 2.1 on a scale from 0 to 10 but did not correlate with the sensitivity levels. CONCLUSION: In patients with RA, no direct relationship between pain intensity and plantar foot loading was found. The decreased tactile sensitivity may be indicative of a disturbed sensation for high plantar pressures. Therefore, pedography can be useful as an additional tool in the detection of excessive forefoot loading before complications are manifested.     

Severe peripheral neuropathy and elevated plantar pressures causing foot ulceration in pituitary gigantism

We report two patients with treated pituitary gigantism and peripheral neuropathy, one of whom has chronic foot ulceration. Detailed neurophysiologfcal assessment was performed on both patients. The patient with foot ulceration had clinical and neurophysiological evidence of severe neuropathy, whereas the patient without ulceration had only neurophysiological abnormalities. The sweating response to acetylcholine was markedly impaired in the feet of both patients, suggesting pedal autonomic denervation. Neither patient had evidence of diabetes mellitus and detailed investigation failed to reveal an alternative cause of peripheral neuropathy. Optical pedobarography revealed abnormally high pressure (>10 kg/cm²) under the metatarsal heads of both patients, one such area coinciding with the area of ulceration. Thus in pituitary gigantism elevated plantar pressures may contribute to the development of foot ulceration when severe peripheral neuropathy Is present. Furthermore, as in diabetes mellitus, impaired sweating may also increase the risk of ulceration as the resultant dry skin may develop fissures.     

Morphofunctional characteristics of the foot in patients with diabetes mellitus and diabetic neuropathy

AimsTo determine the structural and biomechanical characteristics associated with the conditions diabetes mellitus and diabetic neuropathy.MethodsObservational study of 788 patients conducted between February 2007 and February 2009, which included subjects with and without diabetes mellitus who had no active ulcer at enrollment. Demographic variables and the general and specific history of diabetes mellitus were recorded. The patient's foot type according to the Foot Posture Index, joint mobility and deformity were recorded.ResultsNo associations were found between the different foot types (neutral, pronated and supinated) and the structural and demographic variables at a general level, except for the pronated foot that was associated with a higher body mass index, longer suffering from diabetes and the presence of neuropathy [p < 0.001, OR (95% CI): 6.017 (4.198–8.624); p < 0.001, OR (95% CI): 1.710 (1.266–2.309); p = 0.010, OR (95% CI): 0.759 (0.615–0.937), respectively].ConclusionsThe confluence of risk factors such as neuropathy, body mass index, duration of diabetes and limited joint mobility in patients with diabetes mellitus and pronated foot may be a high-risk anthropometric pattern for developing associated complications such as Charcot foot. A prospective analysis of these patients is required to define the risk for developing Charcot neuroarthropathy.