Cytotoxic T Lymphocyte Antigen-4 Gene Variants in Type 2 Diabetic Patients with or without Neuropathy.

Many studies have shown that cytotoxic T lymphocyte antigen-4 (CTLA-4) gene variants are associated with several autoimmune diseases particularly type 1 diabetes. Due to the lack of consistent data for this association with type 2 diabetes (T2D), this study explored the possible influence of CTLA-4 gene polymorphisms at -1722 (T/C), -318 (C/T), and +49 (G/A) positions for susceptibility to T2D in relation with neuropathy. One hundred and eleven unrelated patients with T2D [49 patients with diabetic peripheral neuropathy (DPN) and 62 patients without PDN] and 100 healthy ethnic- and gender-matched controls were included in this study. The dimorphisms at -1722 (C/T), -318 (C/T) and +49 (A/G) for CTLA-4 gene were determined using ARMS-PCR. The CTLA-4 (+49 G/G) and (+49 A/A) genotypes were found to be positively and negatively associated with T2D, respectively (p=0.03). The -318 C/T and T/T genotypes were more frequent in patients than controls and -318 C/C genotype was shown to be protective for T2D (p=0.003). ACT and GTT Haplotypes were less and more frequent in controls and patients, respectively (p=3.86×10-7 and p=2.29×10-5). Genotypes distribution among T2D patients with and without DPN compared to healthy controls showed significantly lower frequencies for -318 C/C and +49 A/A genotypes and significantly higher frequencies for -318 C/T and T/T genotypes as well. Our findings indicate that CTLA-4 (+49 A/G) and (-318 C/T) genotypes could be considered as genetic risk factors associated with susceptibility or protection for T2D.

Diabetic peripheral neuropathy class prediction by multicategory support vector machine model: a cross-sectional study.

OBJECTIVES: Diabetes is increasing in worldwide prevalence, toward epidemic levels. Diabetic neuropathy, one of the most common complications of diabetes mellitus, is a serious condition that can lead to amputation. This study used a multicategory support vector machine (MSVM) to predict diabetic peripheral neuropathy severity classified into four categories using patients' demographic characteristics and clinical features. METHODS: In this study, the data were collected at the Diabetes Center of Hamadan in Iran. Patients were enrolled by the convenience sampling method. Six hundred patients were recruited. After obtaining informed consent, a questionnaire collecting general information and a neuropathy disability score (NDS) questionnaire were administered. The NDS was used to classify the severity of the disease. We used MSVM with both one-against-all and one-against-one methods and three kernel functions, radial basis function (RBF), linear, and polynomial, to predict the class of disease with an unbalanced dataset. The synthetic minority class oversampling technique algorithm was used to improve model performance. To compare the performance of the models, the mean of accuracy was used. RESULTS: For predicting diabetic neuropathy, a classifier built from a balanced dataset and the RBF kernel function with a one-against-one strategy predicted the class to which a patient belonged with about 76% accuracy. CONCLUSIONS: The results of this study indicate that, in terms of overall classification accuracy, the MSVM model based on a balanced dataset can be useful for predicting the severity of diabetic neuropathy, and it should be further investigated for the prediction of other diseases.

HLA class II alleles and risk for peripheral neuropathy in type 2 diabetes patients.

The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. This study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. T2D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group (P = 0.04). HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 and P = 0.05 respectively). Also, patients with severe neuropathy showed higher frequencies of DRB1*07 (P = 0.003) and DQB1*02 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB1 and DQB1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our findings implicate a possible protective role of HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype against development of peripheral neuropathy in T2D patients. Therefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.

Amitriptyline 2% cream vs. capsaicin 0.75% cream in the treatment of painful diabetic neuropathy (Double blind, randomized clinical trial of efficacy and safety).

Because of less systemic side effects of topical medications in pain relief of the painful form of diabetic peripheral neuropathy, this study aimed to compare the effect of amitriptyline and capsaicin cream in relieving pain in this condition. In this randomized, double-blind and non -inferiority trial, 102 patients received amitriptyline 2% and capsaicin 0.75% creams 3 times a day for 12 weeks on the feet. Pain relief was measured by the visual analog scale (0-10). Treatment responding was considered as cure rate greater than 50% from baseline. Evaluations of the pain severity, compliance and drugs adverse effects were performed at each of the 4-week follow -up visits. Both drugs significantly relieved pain in 12 weeks compared with baseline values (P < 0.001 for both). Treatment responders were similar in both groups (P = 0.545). Intention-To-Treat analysis showed no significant difference in the efficacy between the two treatments (P = 0.703). Adverse events were more common in capsaicin group (P = 0.001). Dermatologic complications were the most common: itching, blister formation and erythema in the capsaicin group and skin dryness and itching in the amitriptyline group. This study demonstrates the similar efficacy of amitriptyline cream with capsaicin cream in managing diabetic neuropathic pain with fewer side effects.

A randomized clinical trial of efficacy and safety of the topical clonidine and capsaicin in the treatment of painful diabetic neuropathy.

BACKGROUND: Incomplete efficiency of oral medications restricts their therapeutic success in pain control of the painful form of the diabetic peripheral neuropathy (DPN). Use of topical medications because of less systemic side effects is more acceptable. This study aimed to compare the effect of clonidine gel and capsaicin cream in relieving pain associated with DPN. MATERIALS AND METHODS: This 12-week, randomized, double-blind and parallel-group trial was conducted to compare the efficacy and safety of topical clonidine and capsaicin. Totally, 139 patients with type 2 diabetes with a pain score of at least 4 as assessed by visual analog scale (VAS), were treated for up to 3 months. The endpoint of the study was the reduction in the median pain score from baseline, as assessed by the VAS at the 4 weekly follow-up visits. RESULTS: The intention-to-treat population for the efficacy analysis consists of 69 patients receiving clonidine and 70 patients receiving capsaicin. Both drugs significantly relieved pain at 12 weeks (P < 0.001 for both) but no significant difference in the efficacy between the two treatments was observed (P = 0.931). Dermatologic complications were more common in capsaicin group (P = 0.001). CONCLUSION: The results of this study showed the comparable efficacy of clonidine gel in comparison with capsaicin cream in the treatment of pain due to DPN with less adverse events. More studies are required to better evaluate the efficacy and safety of this topical compound for relieving pain in DPN.

Association between serum uric acid level and diabetic peripheral neuropathy (A case control study).

BACKGROUND: The role of uric acid is well known for the development of nephropathy and retinopathy in diabetic patients. The aim of this study was to evaluate the serum uric acid levels in patients with or without diabetic neuropathy (DPN). METHODS: Forty-two patients with DPN (case group) and 42 patients without DPN (control group) matched with regard to age, gender, body mass index (BMI) and duration of their disease were entered into the study. The diagnosis of DPN was based on the nerve conduction studies on sural, peroneal and tibial nerves in lower limbs. Serum uric acid was measured in these two groups. RESULTS: The mean age of the patients in the case group was 54.6±6.9 and in the control group was 55.8±5.8 years (p=0.389). The demographic characteristics of the patients in these two groups were equal, but only the history of diabetic foot ulcer was higher in patients with DPN (p<0.05). The mean serum uric acid was 4.70±0.96 in diabetic patients with DPN and 4.36±0.89 mg/dl in patients without DPN (p=0.019). CONCLUSION: The results show the higher level of serum uric acid level in diabetic patients with diabetic neuropathy. Further studies are required to determine the role of uric acid in the development and progression of DPN.

Prevalence and risk factors of five most common upper extremity disorders in diabetics.

BACKGROUND: In addition to macrovascular and along with other microvascular complications, diabetic patients suffer from some common musculoskeletal complications. The aim of this study was to assess the prevalence of five musculoskeletal disorders of upper extremity including shoulder capsulitis (SC), limited joint mobility (LJM), Dupuytren's contracture (DC), carpal tunnel syndrome (CTS), and trigger finger (TF) as well as identify their related risk factors in diabetic patients. METHODS: We recruited 432 types 1 or 2 diabetic patients and evaluated them for the presence of musculoskeletal disorders and their-related risk factors in 2012-13. The patients were examined by an endocrinologist and then suspected subjects evaluated by a rheumatologist for defining final diagnosis. RESULTS: The most prevalent musculoskeletal disorder of upper extremity was SC (8.79%), followed by CTS (8.56%), LJM (6.94%), DC (7.4%), and TF (6.71%). Advanced age, female sex, smoking, and duration of diabetes were associated with the appearance of SC; female sex and duration of diabetes with CTS; advanced age and smoking with LJM; advanced age, duration of diabetes and history of foot ulcer with DC; and history of laser photocoagulation was associated with TF. CONCLUSIONS: The results show lower prevalence of upper musculoskeletal disorders and different associated risk factors in our diabetic population in comparison with previous studies on other populations.

The prevalence and associated risk factors of peripheral diabetic neuropathy in Hamedan, Iran.

BACKGROUND: Diabetic neuropathy is one of the most common complications of diabetes mellitus, of which it's most prevalent form is chronic sensorimotor neuropathy. The aim of this study is to assess the prevalence of diabetic peripheral neuropathy (DPN) and its associated risk factors among diabetic patients who reside in Hamedan, Iran. METHODS: A cross-sectional study of 600 types 1 and 2 diabetic patients was performed using the standard Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS) criteria for the diagnosis of diabetic neuropathy. RESULTS:  Overall prevalence of DPN in this population was 45.7% (95% CI: 42.6%-48.8%). The prevalence of DPN in type 1 diabetic patients was 21.5%, whereas in type 2 diabetic patients it was 49.3% (P < 0.001). Duration of diabetes and education level were significantly associated with DPN in type 1 diabetic patients and a history of foot ulcer, age, duration of diabetes, weight, education level, and sex had a significant association with DPN in type 2 diabetic patients according to multiple logistic regression analysis. CONCLUSION: The results of our study showed a relatively high prevalence of DPN in our diabetic population. A significant difference existed in the prevalence of DPN between types 1 and 2 diabetic patients.

Grape seed extract to improve liver function in patients with nonalcoholic fatty liver change.

BACKGROUND/AIM: Therapeutic interventions in nonalcoholic fatty liver disease are limited, while anti-oxidative materials have shown benefits in animal models. This study aimed to evaluate grape seed extract as an anti-oxidative material in this process. Therapeutic effects of grape seed extract were evaluated in comparison to vitamin C in a double-blind setting. MATERIALS AND METHODS: Fifteen patients were enrolled in each group. Liver function tests were done; also, grade of steatosis and pattern of echogenicity of the liver were determined. Patients were followed up by the same evaluation repeated in first, second and third months. RESULTS: Mean age +/- standard deviation was 43.2 +/- 10.3 years. Grape seed extract (GSE) significantly improved the grade of fatty liver change; and resulted in significant decrease in alanine aminotransferase in patients receiving the concentrate compared to those receiving vitamin C independently, from the initial grade of steatosis. CONCLUSIONS: This study describes the beneficial effect of using grape seed extract for three months in patients with nonalcoholic fatty liver disease. These results may improve with a longer period of follow-up.

N-acetylcysteine improves liver function in patients with non-alcoholic Fatty liver disease.

BACKGROUND AND AIMS: Non-alcoholic fatty liver change is a common disease of the liver in which oxidative stress plays a basic role. Studies are largely focused on protecting the liver by means of anti-oxidative material. The aim of this study is to evaluate the role of N- acetylcysteine in the process of liver injury. METHODS: Thirty patients with non-alcoholic fatty liver steatosis were randomly selected to receive either N-acetylcysteine or vitamin C. Liver function tests (alanine aminotransfrase, aspartate aminotransfrase and alkaline phosphatase) were measured as well as the grade of steatosis, the pattern of its echogenicity, the span of the liver and the spleen and the portal vein diameter before the intervention. Patients were followed up using the same method of evaluation repeated in the first, second and third months. RESULTS: The mean age (SD) was 40.1(12.4) in patients receiving NAC and 46(10.4) years in patients receiving vitamin C (P = 0.137). NAC resulted in a significant decrease of serum alanine aminotransfrase after three months, compared to vitamin C. This effect was independent of the grade of steatosis in the initial diagnosis. NAC was able to significantly decrease the span of the spleen. CONCLUSIONS: N-acetylcysteine can improve liver function in patients with non-alcoholic fatty liver disease. Better results may be achievable in a longer follow up.