Characterization of the Metabolic Proteome of Serum From Patients With Diabetic Distal Symmetric Polyneuropathy.

AIMS: The pathophysiological of diabetic distal symmetric polyneuropathy (DSPN) remains to be elucidated and there are no diagnostic or prognostic biomarkers for the condition. In this explorative proteomic study, metabolic proteome profiling of serum in patients with/without DSPN was analyzed. We aimed to discover proteins with different abundance ranges through proximity extension assay (PEA) technology. METHODS: Temperature quantitative sensory testing (QST) and electromyography (EMG) were used to access the small- and large-fiber function of all participants, respectively. The metabolic proteome profile of serum was analyzed using PEA technology (Olink Target 96 METABOLISM panel). RESULTS: We evaluated serum from patients without DSPN (n = 27), with small-fiber neuropathy (SFN, n = 25) and with mixed small- and large-fiber neuropathy (MSLFN, n = 24). Fifteen proteins, which were especially related to immune response, insulin resistance, and lipid metabolism, were significantly different between patients without DSPN and with MSLFN. Besides, seven proteins, especially related to extracellular structure organization, were significantly different between serum from patients with SFN and with MSLFN. What's more, serum from patients without DSPN showed that three proteins, related to immune response, altered significantly compared to serum from patients with SFN. CONCLUSIONS: This was the first study that characterized the metabolic proteomic profile of serum in DSPN patients by analyzing a panel of 92 metabolic proteins using PEA technology.

Ultra-high performance liquid chromatography coupled to tandem mass spectrometry-based metabolomics study of diabetic distal symmetric polyneuropathy.

AIMS/INTRODUCTION: Distal symmetric polyneuropathy (DSPN) is a common complication of type 2 diabetes mellitus, but the underlining mechanisms have not yet been elucidated. The current study was designed to screen the feature metabolites classified as potential biomarkers, and to provide deeper insights into the underlying distinctive metabolic changes during disease progression. MATERIALS AND METHODS: Plasma metabolite profiles were obtained by the ultra-high liquid chromatography coupled to tandem mass spectrometry method from healthy control participants, patients with type 2 diabetes mellitus and patients with DSPN. Potential biomarkers were selected through comprehensive analysis of statistically significant differences between groups. RESULTS: Overall, 938 metabolites were identified. Among them, 12 metabolites (dimethylarginine, N6-acetyllysine, N-acetylhistidine, N,N,N-trimethyl-alanylproline betaine, cysteine, 7-methylguanine, N6-carbamoylthreonyladenosine, pseudouridine, 5-methylthioadenosine, N2,N2-dimethylguanosine, aconitate and C-glycosyl tryptophan) were identified as the specific biomarkers. The content of 12 metabolites were significantly higher in the DSPN group compared with the other two groups. Additionally, they showed good performance to discriminate the DSPN state. Correlation analyses showed that the levels of 12 metabolites might be more closely related to the glucose metabolic changes, followed by the levels of lipid metabolism. CONCLUSIONS: The finding of the 12 signature metabolites might provide a novel perspective for the pathogenesis of DSPN. Future studies are required to test this observation further.

[Neurotrophic therapy in the treatment of a comorbid patient with cerebrovascular pathology and diabetes mellitus]. / Neirotroficheskaya terapiya komorbidnykh bol'nykh s tserebrovaskulyarnoi patologiei i sakharnym diabetom.

OBJECTIVE: To study the use of Cellex in a population of patients aged 45 to 75 years with ischemic stroke and TIA, with a history of type 2 diabetes mellitus (T2DM), with diabetic distal symmetric polyneuropathy. MATERIAL AND METHODS: The study involved 80 patients (men - 52.5%, women - 47.5%) in the rehabilitation period of stroke, including TIA, developed in T2DM. The patients were divided into 2 groups (40 people in each): in the 1st group, patients received Cellex 1.0 ml subcutaneously 1 time per day in addition to routine practice; the 2nd group received only routine practice. Cellex was prescribed in the form of two 10-day treatment courses with a break of 1 month. The range of patients examination during the whole study period (4 visits, 65 days) included an assessment of neurological symptoms (NIHSS, NISLL, DN-4, TSS scales), neurophysiological examination (EMNG), analysis of daily activity (SF-36 questionnaire, the Rivermead Mobility Index, the Modified Rankin Scale), the emotional state assessment on the scale and the effects of therapy on the Clinical Global Impression Scale. RESULTS AND CONCLUSION: The clinical efficacy of the drug was shown in the form of an improvement of clinical parameters and data on EMNG of the lower extremities on the 60th day of the study. Improvement was observed in 17.5% of patients in the 1st group, while in the 2nd group deterioration was observed in 15.0% of patients, as evidenced by the presence of statistically significant differences. The study drug was also shown to be well tolerated and safe. CONCLUSION: The use of the Cellex is effective and safe in patients with T2DM in the recovery period of stroke.

Chinese herbal medicine TangBi Formula treatment of patients with type 2 diabetic distal symmetric polyneuropathy disease: study protocol for a randomized controlled trial.

BACKGROUND: Diabetic distal symmetric polyneuropathy (DSPN) is one of the most common microvascular complications of diabetes mellitus, and it has become a major public health problem worldwide because of its high and increasing prevalence, morbidity, and disability rate. The current medications for DSPN are not entirely satisfactory. Preliminary studies indicated that the Chinese herbal TangBi Formula may alleviate signs and symptoms and improve the velocity of nerve conduction in patients with DSPN. This study was designed to determine if Chinese herbal medicine used in combination with conventional treatment is more effective than conventional treatment alone. METHODS/DESIGN: We are conducting a multicenter, placebo-controlled, double-blind, randomized, controlled clinical trial as a means of assessing the therapeutic effects of traditional Chinese medicine (TCM) treatment. A total of 188 patients will be randomized in a 1:1 ratio to a treatment group (TangBi Formula plus mecobalamin) and a control group (placebo plus mecobalamin). The test period lasts 6 months, during which all of the patients will be given standard medical care as recommended by established guidelines. The primary outcome will be development of differences in changes in clinical symptoms and signs in patients and changes in Michigan Diabetic Neuropathy Score (MDNS) between the two groups before and after treatment. The secondary outcome will be changes in nerve conduction velocity and in single clinical signs and symptoms. Safety assessments and adverse events will also be evaluated. DISCUSSION: We postulate that patients with DSPN will benefit from therapy that includes TCM. If successful, this work will provide an evidence-based complementary therapeutic approach for treatment of DSPN. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03010241 . Registered on 2 January 2017.

Pro198Leu missense polymorphism of the glutathione peroxidase 1 gene might be a common genetic predisposition of distal symmetric polyneuropathy and macrovascular disease in Japanese type 2 diabetic patients.

UNLABELLED: Aims/Introduction: We have previously reported that the Pro198Leu missense polymorphism in the glutathione peroxidase 1 (GPx-1) gene was associated with frequent macrovascular disease (MVD). Our goal was to examine whether the GPx-1 genotype is associated with diabetic neuropathy. MATERIALS AND METHODS: We determined the GPx-1 genotype in 173 Japanese type 2 diabetic patients who received medical interviews, physical examinations, nerve conduction studies, quantitative vibratory perception (QVP), head-up tilt and heart rate variability tests by polymerase chain reaction-restriction fragment-length polymorphism. Diabetic sensorimotor distal symmetric polyneuropathy (DSPN) and diabetic autonomic neuropathy (DAN) were evaluated separately. DSPN and DAN were defined by two or more abnormalities of neuropathic leg symptoms, diminished Achilles tendon reflexes or impaired QVP in toes, and two autonomic dysfunctions, respectively. The association of the GPx-1 genotype with DSPN, DAN, MVD and other clinical manifestations was analyzed. RESULTS: The prevalence of DSPN, impaired QVP and painful leg cramps in patients having a genotype with Pro/Leu at the codon 198 (Pro/Leu type) was significantly higher than those with Pro/Pro type. As a result of multivariate analyses that contained the GPx-1 genotype as an independent variable, the Pro/Leu type was extracted as a significant risk factor of DSPN, QVP impairment and MVD. The statistical significance did not disappear, even after proteinuria, retinopathy and a history of MVD were introduced as independent variables. In contrast, the GPx-1 genotype was not associated with DAN. CONCLUSIONS: The Pro198Leu missense polymorphism of the GPx-1 gene might have a common genetic predisposition to DSPN and MVD. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00127.x, 2011).