Diabetic Peripheral Polyneuropathy Research Articles

Современные методы диагностики диабетической периферической полинейропатии, вопросы лечения и профилактики

ABSTRACT INTRODUCTION. Diabetic peripheral neuropathy occurs in more than half of patients with type 1 or type 2 diabetes mellitus. Diabetic peripheral neuropathy develops as a result of demyelination, which leads to pain, early disability, followed by a decrease in the quality of life. MATERIAL AND METHODS. A systematic search was conducted for studies based on the RSCI and PubMed databases for the period from 2019 to 2023 on the topic of modern methods of diagnosing diabetic peripheral polyneuropathy, prevention and treatment in adult patients, which gave 929 matches. We have analyzed 40 scientific publications. DISCUSSION. Timely early diagnosis improves the clinical outcomes of diabetic polyneuropathy. In type 1 diabetes, hyperglycemia is the main risk factor for complications, and glycemic control, in turn, prevents the development of the diabetic peripheral neuropathy. In type 2 diabetes, the main risk factor for the development of the diabetic peripheral neuropathy is metabolic syndrome. CONCLUSION. Confocal microscopy of the cornea, along with nociceptive evoked potentials, is a promising method for detecting early signs of diabetic polyneuropathy. The use of sodium-glucose cotransporter -2 inhibitors represents a new direction in the prevention and treatment of diabetic polyneuropathy. KEYWORDS: diabetic peripheral neuropathy, diabetes mellitus, quality of life, alpha-lipoic acid, confocal microscopy of the cornea

Ocular surface changes in mice with streptozotocin-induced diabetes and diabetic polyneuropathy

PurposeDiabetes mellitus (DM) is a leading risk factor for corneal neuropathy and dry eye disease (DED). Another common consequence of DM is diabetic peripheral polyneuropathy (DPN). Both complications affect around 50 % of the DM patients but the relationship between DM, DED and DPN remains unclear. MethodsIn this study, we examined mice with early onset of DM and PN after streptozotocin (STZ)-induced diabetes (DPN). We compared the early morphological changes of the sciatic nerve, dorsal root and trigeminal ganglia with the changes in the ocular surface, including tear proteomic and we also investigated respective changes in the gene expressions and morphological alterations in the eye tissues involved in tear production. ResultsThe lacrimal gland, conjunctival goblet cells and cornea showed morphological changes along with alterations in tear proteins without any obvious signs of ocular surface inflammation. The gene expression for respectively altered tear proteins i.e., of Clusterin in cornea, Car6, Adh3a1, and Eef1a1 in eyelids, and Pigr in the lacrimal gland also showed significant changes compared to control mice. In the trigeminal ganglia like in the dorsal root ganglia neuronal cells showed swollen mitochondria and, in the latter, there was a significant increase of NADPH oxidases and MMP9 suggestive of oxidative and neuronal stress. In the dorsal root ganglia and the sciatic nerve, there was an upregulation of a number of pro-inflammatory cytokines and pain-mediating chemokines. ConclusionThe early ocular changes in DM Mice only affect the lacrimal gland. Which, is reflected in the tear film composition of DPN mice. Due to the high protein concentration in tear fluid in humans, proteomic analysis in addition to noninvasive investigation of goblet cells and cornea can serve as a tools for the early diagnosis of DPN, DED in clinical practice. Early treatment could delay or even prevent the ocular complications of DM such as DED and PN.

Electrochemical skin conductances values and clinical factors affecting sudomotor dysfunction in patients with prediabetes, type 1 diabetes, and type 2 diabetes: A single center experience

Background and aimSudomotor dysfunction is linked to small fibers damage. We investigated sudomotor dysfunction in a large group of participants with diabetes, prediabetes, and nondiabetic healthy subjects. This study aimed to complete knowledge on sudomotor dysfunction in this population, especially regarding the threshold values for the electrochemical skin conductance (ESC) and factors affecting it. Materials and methodsA total of 690 volunteers in four groups were included in the study (type 1 [T1DG]: n = 80, 61.3% women; type 2 diabetes [T2DG]: n = 438, 63.5% women; prediabetes [Pre-DG]: n = 88, 80.7% women; healthy control [HC-G]: n = 84, 67.5% women). All subjects were investigated for clinical diabetic peripheral polyneuropathy and sudomotor dysfunction. The characteristics of participants obtained from outpatient records were evaluated. We used the Sudoscan device to measure ESC which was normalized for BMI, to improve the discriminative capability of the method. ResultsDiabetic polyneuropathy was found in 17.5% of T1DG, 27.4% of T1DG, and 10.2% of Pre-DG. The mean ESC/BMI was lower in subgroups with diabetic polyneuropathy than those without. Mean ESC/BMI was lowest in T2DG and highest in HC-G but comparable in T1DG and Pre-DG. We accepted the “mean ESC/BMI-1 SD” in the HC-G as the threshold for sudomotor dysfunction. Accordingly, the prevalence of sudomotor dysfunction was 18.8%, 44.3%, 59.1%, and 15% in T1DG, T2DG, Pre-DG, and HC-G, respectively. In T2DG, sudomotor dysfunction was found in 66.7% of persons with retinopathy, of which 56.3% had clinical diabetic polyneuropathy. The prevalence of sudomotor dysfunction in subjects with peripheral artery disease, chronic kidney disease, cardiovascular disease, and hypertension was 46.7%, 47.4%, 43.4%, and 50%, respectively, and 42.9%, 38.9%, 45.5%, and 37.3% of whom in the same order detected with clinical diabetic polyneuropathy. Considering the entire group, a logistic regression model demonstrated that the variables associated with SMD were: retinopathy (OR: 2.969; 95% CI: 1.723, 5.114), female gender (OR: 1.952; 95% CI: 1.287, 2.962), and e-GFR (OR: 0.989; 95% CI: 0.981, 0.998). Since the rate of complications was very low in T1DG, excluding this group, a new model similarly revealed that retinopathy and female gender were associated with SMD, however, the association with e-GFR was disappeared. ConclusionThe prevalence of sudomotor dysfunction is high when established peripheral polyneuropathy was present in diabetes. Even though, sudomotor dysfunction can also occur before clinical polyneuropathy in both types of diabetes (T1DG: 18.8%, T2DG 44.3%), prediabetes (59.1%), and nondiabetic healthy subjects (15%). The variables associated with sudomotor dysfunction were retinopathy and female sex. Normalization of ESC for BMI would be a beneficial approach. However, before this method is included in the routine screening programs for diabetic polyneuropathy, large-scale and prospective studies are required to reach a consensus on the pathological threshold values.

N°300 – The value of the dorsal sural nerve in the evolutive diabetic peripheral polyneuropathy

N°300 – The value of the dorsal sural nerve in the evolutive diabetic peripheral polyneuropathy

Safety and efficacy of duloxetine versus gabapentin in painful diabetic polyneuropathy

To evaluate safety and efficacy of Gabapentin and Duloxetine in patients with painful diabetic neuropathy.This is a prospective randomized double blinded parallel group study done for a period of 12 weeks. Total of 60 patients were enrolled and randomly allocated to two groups with 30 patients each, group A received Duloxetine 30 mg twice daily and group B received Gabapentin 300mg twice daily and followed every 2 weeks. Patients of age 35 to 60 years with painful diabetic peripheral polyneuropathy are included in the study. Primary objective is improvement in pain assessed by NPRS; Secondary objective is improvement in sleep and clinical condition of the patient, assessed by Sleep Interference Score and Clinical Global Impression of Change (CGIC). Assessment was done at beginning and at four, eight and twelve weeks. Data was analysed using SPSS 12.0 version.Numerical pain rating scores and daily sleep interference scores were reduced significantly with course of treatment within both groups (p = <0.05 in both groups), but there was no significant difference observed between two groups at baseline, 4th week, 8th week and 12th week. There is significant reduction in CGIC severity scores with course of treatment within both groups (p = <0.05 in both groups), but there was no significant difference observed between groups at baseline and at end of treatment. Common adverse events seen are nausea, dry mouth, dizziness, somnolence and constipation in both groups. There is high incidence of nausea and dry mouth with Duloxetine when compared to Gabapentin.Monotherapy with either Duloxetine or Gabapentin was equally effective at 12 weeks treatment with minor side effects. In addition, Gabapentin showed fewer side effects. It can be concluded that for preventing side effects, Gabapentin can be used. Further large head to- head comparator and combination trials are required.

Recent updates in the treatment of diabetic polyneuropathy.

Distal symmetric diabetic peripheral polyneuropathy (DPN) is the most common form of neuropathy in the world, affecting 30 to 50% of diabetic individuals and resulting in significant morbidity and socioeconomic costs. This review summarizes updates in the diagnosis and management of DPN. Recently updated clinical criteria facilitate bedside diagnosis, and a number of new technologies are being explored for diagnostic confirmation in specific settings and for use as surrogate measures in clinical trials. Evolving literature indicates that distinct but overlapping mechanisms underlie neuropathy in type 1 versus type 2 diabetes, and there is a growing focus on the role of metabolic factors in the development and progression of DPN. Exercise-based lifestyle interventions have shown therapeutic promise. A variety of potential disease-modifying and symptomatic therapies are in development. Innovations in clinical trial design include the incorporation of detailed pain phenotyping and biomarkers for central sensitization.

Impact of pain severity on functioning domains, sleep, and cognition in painful diabetic peripheral polyneuropathy patients

BackgroundSeveral studies have observed that painful diabetic peripheral polyneuropathy (PDPN) had an impact on the level of functioning domains and quality of sleep as well as cognitive functions. This study is aimed to explore the relationship between severity of pain and level of functioning, sleep quality, and cognitive functions among these patients. We recruited 100 diabetics with a mean HbA1C% of 7.3±0.9, diagnosed with PDPN, and included in the study with a mean age of 51±12.8 years and disease duration of 10.2±7.4 years. The following assessment was done for each patient; clinical and neurophysiology assessment, routine laboratory assessment, measuring pain severity, and average pain severity interference scores using pain visual analog scale (VAS) and brief pain inventory (BPI) short form, respectively, sleep quality assessment using Pittsburgh Sleep Quality Index (PSQI) and Montreal cognitive function assessment (MOCA) scales.ResultsModerate to severe pain was recorded in 71% of patients according to the VAS pain score. The severe pain group recorded the significant highest average pain severity and interference scores in BPI and domains compared to other less pain groups with average pain intensity scores of 7.5±0.6 vs 5.3±0.8 in the moderate and 3.3±0.4 in mild pain groups. Poor sleep quality and pattern were observed in these patients with a mean PSQI score of 6.8±3.1, and the severe pain group had a significant highest score of 9.4±2.3 compared to other less group scores of 7±2.3 and 3.7±1.8. Their mean MOCA score was low 24.2±2.2. Out of them 48/100 patients had mild cognitive impairment and recorded high frequency in the severe pain group (28/32) followed by the moderate pain (15/39) group. There is a significant correlation between the score of VAS and PSQI as well as MOCA.ConclusionsPainful DPN patients had a poor level of functioning and sleep quality as well as cognitive impairment based on pain intensity.Trial registrationThis study was registered on a clinical trial with registration number NCT03275233 on 7 September 2017.

The relation between serum uric acid levels and diabetic peripheral neuropathy in type 2 diabetes in Guilan, north of Iran

BackgroundDiabetic peripheral neuropathy (DPN) is one of the most common chronic microvascular complications in type 2 diabetes mellitus (T2DM). Hence, the present study aimed to investigate the association between Serum Uric Acid (SUA) levels and diabetic peripheral polyneuropathy in patients with type 2 diabetes.MethodsWe performed this case–control study during 2019–2020 on individuals with diabetes referring to the Razi clinic of Rasht, in the north of Iran. Polyneuropathy in patients was assessed based on the Neuropathy Disability Score (NDS), Diabetic neuropathy symptom score (DNS) scoring system, and electromyography (EMG)/nerve conduction velocity (NCV). The inclusion criterion for the control group was normal EMG/NCV. Then, the patients were assessed for SUA level and also laboratory results.ResultsIn total, 230 patients with type 2 diabetes were examined. The mean SUA level in the DPN group was significantly higher compared to the control group (6.72 ± 1.75 vs. 4.57 ± 1.49 mg/dL). With increasing the SUA, the odds of developing neuropathy increased by 2.2 times (OR = 2.2). The risk factors for diabetic polyneuropathy included gender (male) (OR = 0.347), SBP (OR = 1.1), retinopathy (OR = 3.29), and microalbuminuria (OR = 4.44). The chance of developing polyneuropathy in patients with retinopathy was 3.3 times higher than in the control group, it was 4.4 times in microalbuminuria patients.ConclusionElevated SUA level increased the chance of developing peripheral polyneuropathy in a person with type 2 diabetes. SUA levels higher than 5.25 mg / dL expose a person with type 2 diabetes to developing peripheral polyneuropathy.

Protein arginine N-methyltransferase 1 gene polymorphism is associated with proliferative diabetic retinopathy in a Japanese population.

To investigate the effects of single-nucleotide polymorphisms (SNPs) around the protein arginine N-methyltransferase 1 (PRMT1) gene on the incidence and severity of diabetic retinopathy (DR). A total of 310 Japanese patients with type 2 diabetes mellitus (T2DM) were investigated. Genotyping of ten tagged SNPs were performed by quantitative real-time polymerase chain reaction (qRT-PCR). The association between each SNP genotype and diabetic microangiopathy was assessed using univariate analysis in a dominant model of the minor alleles followed by multivariate logistic regression analysis with the propensity score matching (PSM) method. The effect of disease-related SNP on PRMT1 and hypoxia-inducible factor-1α (HIF-1α) mRNA levels in vivo was evaluated by qRT-PCR. In the univariate analysis, the minor A allele at rs374569 and the minor C allele at rs3745468 were associated with DR severity (P = 0.047 and P = 0.003, respectively), but not diabetic nephropathy and peripheral polyneuropathy severity. Multivariate analysis showed that the rs3745468 variant caused an increased incidence of proliferative DR (PDR) (odds ratio 9.37, 95% confidence interval 1.12-78.0, P = 0.039). In the PSM cohort, the patients carrying the rs3745468 variant had lower PRMT1 mRNA levels compared to those without the variant (P = 0.037), and there was an inverse correlation between PRMT1 and HIF-1α mRNA levels (r = -0.233, P = 0.035). The rs3745468 variant in the PRMT1 gene was associated with an increased incidence of PDR in Japanese patients with T2DM and might be involved in the HIF-1-dependent hypoxic pathway through altered PRMT1 levels.

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Development and Comparative Efficacy of Lagos Neuropathy Protocol for Improving Recovery of Symptom and Functional Independence Performance in Individuals with Diabetic Peripheral Sensorimotor Polyneuropathy.

Diabetic peripheral sensorimotor polyneuropathy (DPSP) has been treated with sketchy outcomes and available approaches are not applicable for self-administration. This study developed protocol for managing symptoms of DPSP and assessed its comparative efficacy. Study developed Lagos Neuropathy Protocol (LNP) through existing concept in DPSP and tested its safety, clinical applicability, and ease of self-administration. Its efficacy was compared with Buerger-Allen Exercise (BAE) by involving 31(11males) with DPSP, randomized into LNP and BAE and treated for 10-week. Toronto Clinical Scoring System was used to diagnose DPSP while Diabetic Neuropathy Examination was used to diagnose distal polyneuropathy. Sensory/pressure perception was assessed using 10 g-monofilament while Short Physical Performance Battery, Bergs Balance Scale and Visual Analogue Scale was used to assess functional performance, strength and balance, and pain respectively. LNP has three domains: sensory/pressure/proprioception, strength/balance, and pain/swelling. Most (80%) of the participants rated the LNP as excellently safe while the rest (20%) rated as very good in safety. All the participants rated LNP excellent in terms of self-administration and suitability for clinical use without adverse effect. The mean age of the participants for the comparative phase was 66.20±9.48years while their length of diagnoses of diabetes was 15.80±13.35years. About a third (32.5%) had DPSP. Both LNP and BAE had significant improvement (p<0.05) in sensory/pressure perception, pain, strength and balance, and functional performance but LNP had better significant improvement. LNP is safe, good for self-administration, clinically applicable and efficacious in improving sensory/pressure perception, balance, pain and functional performances in individuals with DPSP.

Диабетическая периферическая полинейропатия в практике врача первичного звена

Диабетическая периферическая сенсомоторная нейропатия относится к числу наиболее распространенных осложнений сахарного диабета. Диагностика диабетической периферической нейропатии состоит из оценки симптомов и клинического неврологического обследования с применением количественных тестов для оценки степени выраженности неврологических расстройств. В статье рассматриваются современные подходы к комплексному лечению болевой формы диабетической периферической нейропатии, начиная с компенсации углеводного обмена. Если, несмотря на нормализацию гликемии, у пациента сохраняются жалобы на боли или другие неприятные ощущения, необходимо назначать средства патогенетической либо симптоматической направленности с целью их уменьшения или полного исчезновения. Рассмотрены средства местной терапии для лечения диабетической периферической нейропатии, целью которой является купирование болевой симптоматики (антидепрессанты, противосудорожные средства, анальгетики, средства местного воздействия), а также средства патогенетической терапии, базирующиеся на воздействии на основные патогенетические компоненты диабетической периферической нейропатии (применение препаратов α-липоевой (тиоктовой) кислоты). Diabetic peripheral sensorimotor neuropathy is one of the most common complications of diabetes mellitus. Diagnosis of diabetic peripheral neuropathy consists of symptom assessment and clinical neurologic examination using quantitative tests to assess the severity of neurologic disorders. The article discusses modern approaches to the complex treatment of pain form of diabetic peripheral neuropathy, starting with the compensation of carbohydrate metabolism. If, despite the normalization of glycemia, the patient continues to complain of pain or other unpleasant sensations, it is necessary to prescribe pathogenetic or symptomatic agents in order to reduce or completely disappear. The means of local therapy for the treatment of diabetic peripheral neuropathy, the purpose of which is to relieve pain symptoms (antidepressants, anticonvulsants, analgesics, topical agents), as well as pathogenetic therapy, based on the effect on the main pathogenetic components of diabetic peripheral neuropathy (use of drugs α-lipoic (thioctic) acid).

The silent occurrence of cerebral small vessel disease in nonelderly patients with type 2 diabetes mellitus.

The prevalence of cerebral small vessel disease (SVD) increases in elderly patients with type 2 diabetes (T2DM), exacerbating cognitive decline. However, the prevalence and the severity of SVD in dementia-free nonelderly T2DM patients were largely unknown. Our primary aim is to investigate SVD in such patients, with a specific focus on the correlation between SVD and diabetic peripheral sensorimotor polyneuropathy (DSP). We recruited 180 young and middle-aged subjects without cognitive impairment (106 with T2DM, 74 controls). Signs of cerebral SVD on magnetic resonance image were investigated, and the overall SVD burden was evaluated by a combined score. Patients with T2DM underwent further detailed DSP assessment. Regression models were used to investigate the association of SVD with the presence of T2DM, and the associations of the prevalence and severity of SVD and DSP were also explored in patients with T2DM. The prevalence of microbleeds and overall burden of SVD were significantly higher in T2DM patients than in the controls. Further, the presence of DSP related to an increased risk of SVD after adjustment in diabetic group. Moreover, Toronto Clinical Scoring System values were positively associated with the increased SVD scores, and bilateral sural sensory nerve conduction velocities were negatively associated with increasingly severity of SVD scores. The current findings extended the increasing prevalence of SVD to dementia-free nonelderly patients with T2DM, suggesting that the time for cognitive screening and prevention might be moved forward in T2DM patients, especially for those with DSP.

Asymptomatic Median Neuropathy in Patients with Diabetic Polyneuropathy

Aim: This study aims to investigate whether asymptomatic median neuropathy (AMN) in patients with diabetic peripheral polyneuropathy (DPNP) is a result of polyneuropathic involvement of median nerve (MN) or its true entrapment. Subjects and Methods: We determined the grades of the Michigan severity scale and the rates of peripheral nerve conduction abnormalities in study subgroups, including patients with carpal tunnel syndrome (CTS), AMN, and normal MN conductions to highlight if the severity of polyneuropathic involvement was different between them. In addition, the results of conventional and comparative nerve conduction studies (NCSs) were compared between these study subgroups. Results: Distributions of Michigan grades and rates of abnormalities in peroneal and sural NCSs were similar between the subgroups (P &gt; 0.05 for all analyses). Abnormality rates of ulnar NCSs were higher in the AMN group than in the other groups, whereas those of comparative transcarpal NCSs were higher in the CTS group. The mean distal sensory latency (DSL) and motor latency (DML) of MN were longer, sensory conduction velocity (SCV) was slower in the CTS group than AMN group, whereas MN motor conduction velocity (MCV) was slower, UN DSL was longer, SCV was slower, SNAP amplitude was smaller, DML was longer, and MCV were slower in the AMN group (P &lt; 0.05 for all analyses). Discussion: Our findings reveal that grade of polyneuropathic involvement is more prominent in AMN, whereas transcarpal MN conduction delay is greater in CTS. The results of the study suggest that the prominence of polyneuropathic impairment in addition to a lesser degree of MN sheet compression obscures the clinical signs in patients with diabetes with AMN.

Оцінка ефективності та доцільності застосування засобів фізичної терапії у хворих із діабетичною периферійною полінейропатією

The use of modern pharmacological agents in the treatment of complications of diabetes mellitus does not solve all problems of this severe and diverse pathology, so the search for using of methods of physical therapy and rehabilitation for patients with diabetic peripheral polyneuropathy remains relevant. In addition, an effective combination of medications and physical therapy can accelerate the achievement of diabetes compensation, prevent or cause regression of neurovascular complications. The purpose of the work was to evaluate the efficacy of physical therapy application for patients with diabetic peripheral polyneuropathy in outpatient treatment. Material and methods. We examined 30 patients aged 55-70 years with diabetes mellitus of the 2nd type, complicated by diabetic peripheral polyneuropathy. The patients were divided into two groups depending on the conducting of the proposed physical therapy. A course of physical therapy lasted 3 months and consisted of 36 sessions and relaxation exercises with dosed walking. Dynamic assessment of the severity of manifestations diabetic peripheral polyneuropathy was performed using visual analogue scale and the Questionnaire DN4 (Bouhassira D. et al., 2005). Moderate and severe diabetic peripheral polyneuropathy with the existing pain syndrome, sensory and motor disorders were diagnosed. Results and discussion. The results of the course of physical therapy demonstrated substantial (up to 40%) decrease of severity of diabetic peripheral polyneuropathy symptoms only in patients of the main group. The average subjective pain assessment after a course of physical therapy by the visual analogue scale in patients from the main group was 3.2±1.3 cm, with a variation from 2 to 5 cm. Reduction of pain syndrome as a result of course of physical therapy can be considered objective and significant, because the values of visual analogue scale were different from the previous ones in average of 15.3±1.3 mm. According to the DN4 questionnaire, after the course of physical therapy patients from the main group demonstrated the average values 5.1±0.7 points, with the differences of the score from 4 to 6, which confirmed the presence of a positive influence on the neurovascular complications of diabetes mellitus in patients with diabetic peripheral polyneuropathy. Conclusion. Therefore, an additional prescription of complex physical therapy by its effectiveness demonstrates significant benefits in reducing of the clinical manifestations and progression of diabetic peripheral polyneuropathy in patients with diabetes 2-type in comparison with medical therapy along. The conducted study allowed us to prove the efficiency and to propose the inclusion of complex physical therapy treatment programs for patients with diabetic peripheral polyneuropathy during outpatient treatment

The impact on large fibre function and small fibre function in patients with type 2 diabetes on benfotiamine therapy

Diabetes mellitus (DM) is the leading cause of neuropathy worldwide. Based on the data from several studies, sensorimotor polyneuropathy (diffuse and symmetric neuropathy) will develop within 10 years of the onset of DM in 40 % to 50 % of patients with type 1 and type 2 DM. In patients with type 2 DM, target blood glucose levels are associated with a reduced incidence of neuropathy. Objective — to study the correlation between the stage of diabetic peripheral polyneuropathy in type 2 diabetic patients, and the effects and efficacy of benfotiamine as transketolase activator. Materials and methods. In this study, 190 patients with type 2 DM were screened for DPN. DPN was confirmed in 105 patients displaying both clinical manifestations of neuropathy with a positive Diabetic Neuropathy Symptom (DNS) score and increased vibration perception threshold (VPT) on a biotensiometer. Based on the above stated criteria patients were divided into 4 groups: 1 — with positive DNS score, positive 10 g monofilament test score, VPT between 16—25 volts; 2 — with positive DNS score, positive 10 g monofilament test score, VPT between 26—35 volts; 3 — with positive DNS score, positive 10 g monofilament test score and VPT between 35—40 volts; 4 — control group with positive DNS score, negative 10 g monofilament test score and normal VPT value (n = 25 (23 %); 20 females and 5 males). The first 3 groups received benfotiamine 300 mg daily for 6 weeks, the control group was benfothiamine naïve. All the groups continued their antidiabetic medication. Results and discussion. The diabetic neuropathy score and vibration perception threshold was assessed in 105 patients (84 females and 21 males) with type 2 DM, before starting of benfotiamine 300 mg daily and after 6 weeks of therapy. Results of DNS: differences between group 3 and both group 1 and 2 were significant, but not between group 1 and 2. Patients in group 1 (n = 24), in females (n = 18) the DNS varied from 1—2, and in males (n = 6) the DNS varied from 1—3. After the 6 weeks,DNS score decreased in both females and males i.e. 1—1.25 and 1—2.5 correspondingly. Conclusions. The role of benfotiamine in clinical practice has been demonstrated in many clinical trials with variable trial design, patient groups and history of diabetes. In our study we found that patients with mild neuropathy and vibration perception threshold of 16—25 volts showed a reduction in VPT of up to 16 %, and the patients with moderate neuropathy and reduced vibration perception threshold of 26—35 volts were the ones who benefitted the most from benfotiamine therapy. Benfotiamine activates transketolase and thus helps in the reduction of AGEs formation and associated sugar induced metabolic stress.

Early-Stage Diabetic Neuropathy Reduces Foot Strength and Intrinsic but Not Extrinsic Foot Muscle Size.

Background Tracking progression of diabetic peripheral polyneuropathy (DPN) is usually focused on sensory nerves and subjective testing methods. Recent studies have suggested that distal muscle atrophy may precede sensation loss. Methods to objectively measure distal muscle size and strength are needed to help understand how neuropathy affects muscle function. Purpose To evaluate individual intrinsic and extrinsic foot muscle sizes and functional foot strength in participants with DPN. Methods Thirty individuals participated in this cross-sectional study (15 DPN and 15 matched controls). Sizes of 10 separate muscles of the lower leg and foot were measured using ultrasound imaging. Functional foot strength was also quantified using custom great toe and lateral toe flexion tests along with a doming test. Muscle size and strength metrics were compared between groups using ANOVAs and paired t-tests (α = 0.05). Correlations between strength and relevant muscle sizes were also evaluated. Results The sizes of all four intrinsic foot muscles were smaller in individuals with DPN (p ≤ 0.03), while only one (toe extensor) of the six extrinsic muscles was smaller (p ≤ 0.03), while only one (toe extensor) of the six extrinsic muscles was smaller (p ≤ 0.03), while only one (toe extensor) of the six extrinsic muscles was smaller (p ≤ 0.03), while only one (toe extensor) of the six extrinsic muscles was smaller (r ≤ 0.80) with several corresponding intrinsic muscle sizes. The doming strength test did not show any difference between groups and was moderately correlated with one muscle size (r ≤ 0.80) with several corresponding intrinsic muscle sizes. The doming strength test did not show any difference between groups and was moderately correlated with one muscle size (Conclusion Diabetic peripheral polyneuropathy affects intrinsic muscles before extrinsics. Ultrasound imaging of individual muscles and functional toe flexion tests can be used clinically to monitor DPN progression and foot function. Participants need to be trained in the doming test before a relationship can be established between this test and DPN foot function. Future studies should include muscle quality measurements to better understand characteristics of affected muscles.

The effect of vitamin D therapy on inflammatory markers in patients with type 2 diabetes mellitus and diabetic peripheral polyneuropathy

BACKGROUND: The pathogenesis of diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM) is multifactorial, and includes increased inflammation. In recent years, the effect of vitamin D therapy on improving the profile of inflammatory parameters has been actively studied.&#x0D; AIMS: The aim of this study was to assess inflammation markers before and after various doses of cholecalciferol therapy in T2DM with DPN.&#x0D; MATERIALS AND METHODS: Single-center open randomized study included T2DM patients with PDN. Sixty-seven patients were randomized into 2 groups. For 24 weeks Group I have been taking a dosage of cholecalciferol 5,000 IU/week, and Group II a dosage of 40,000 IU/week. At the baseline and in the end of the research there have been studied body mass index (BMI), glycated hemoglobin (HbA1c), 25-hydroxyvitamin D (25(OH)D), PTH, interleukin-1, -6, -10 (IL), C-reactive protein (CRP), tumor necrosis factor - (TNF).&#x0D; RESULTS: Sixty-two patients completed the study. Group I (n=31, F16), Group II (n=31, F15) were initially compared by age, sex, BMI and НbA1clevel. Vitamin D deficiency/insufficiency was detected in 78% of patients with T2DM. After 24 weeks of therapy with cholecalciferol in Group II there was a significant decrease in BMI, HbA1c, IL-6 levels and an increase in IL-10 levels while no changes were found in Group I. There has been established a correlation between the final level of 25(OH)D and IL-6 (r=-0.378, p=0.036), IL-10 (r=0.483, p=0.006), BMI (r=-0.388, p=0.031) and НbA1c(r=-0.388, p=0.031).&#x0D; CONCLUSION: The intake of cholecalciferol at a dosage of 40,000 IU/week for 24 weeks is associated with a decrease in BMI, improvement of glycemic control and pro-inflammatory markers profile in patients with T2DM with DPN. Study results showed that the normalization of serum 25(OH)D level can be one of the modifying factors for the development and progression of DPN in patients with T2DM.

Описание клинических случаев семейной формы сахарного диабета HNF1A-MODY

Adult type of diabetes mellitus in young people (MODY) is a group of diseases associated with gene mutations leading to pancreatic β-cell dysfunction. There are 14 known variants of MODY, the most studied are MODY 1-5. The article presents a clinical cases of MODY3 which is based on a mutation of the HNF1A gene.We observed 2 families in which young girls of 26 and 25 years old were probands, respectively. Diabetes mellitus (DM) was first diagnosed in them at the age of 16. At the onset of the disease, a patient from 1 family had complaints of a nonspecific nature, glucosuria, hyperglycemia up to 9 mmol/l, HbA1с – 8%. And in a patient from 2 families, hyperglycemia up to 14 mmol/l was detected by chance, there were no complaints. When examined 10 years after the diagnosis of diabetes in both patients, the level of C-peptide was within the reference values, which indicates the preservation of the secretory function of the pancreas. Antibodies in a patient from 1 family were negative, compared with a patient from 2 families (the presence of antibodies to GAD was detected), the level of HbA1с was 7.8% and 5.9%, respectively. Of the concomitant diseases, 2 probands were diagnosed with autoimmune thyroiditis. Diabetic peripheral polyneuropathy was a complication of diabetes in both patients. A burdened family history of carbohydrate metabolism disorders was observed in 2 families and was followed in 3 maternal generations. Based on the age of diagnosis of diabetes, preserved secretion of β-cells of the pancreas, the absence of antibodies, determination of diabetes in relatives in three generations, it was suggested that the patients had HNF1A-MODY. After a molecular genetic study, the diagnosis was confirmed in the observed patient and her mother (family 1) and in a patient from family 2. These clinical cases demonstrate variants of the course of monogenic diabetes.

Thioctic Acid and Vitamin B Complex Improves Clinical Sings in Diabetic Peripheral Neuropathy

Diabetic neuropathy is the most common cause of neuropathy worldwide and it is estimated to affect about half of people with diabetes. The goal of our study is to compare the effectiveness of thioctic acid treatment alone versus the efficacy of thioctic acid plus vitamin B complex in patients with diabetic peripheral polyneuropathy (DPN). We conducted a prospective, observational study staring from October 2017 to December 2018, in which we included 56 DPN patients. Depending on the Michigan neuropathic screening instrument (MNSI) we divided the patients into two subgroups: patients with MNSI [7 and patients whose MNSI did not decrease sufficiently during the therapeutic protocol. 36 patients (64.2%) of the total patients enrolled in the study had an MNSI [7 at one of the follow-up meetings. These patients were also divided according to the therapeutic protocol applied in a group of patients who were treated with only thioctic acid (TA group) and in a group of patients who were treated with thioctic acid plus vitamin B complex (TA + B group). We noticed a greater proportion of patients who had a MNSI [7 in the TA + B group. This study revealed that the treatment of peripheral diabetic neuropathy with thioctic acid plus Vitamin B complex compared to thioctic acid alone was superior in terms of improving clinical features.