Iranian Journal of

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At least 2 million people are affected by type II diabetes mellitus in Iran. Neuropathy is one of the commonest complications of diabetes affecting the quality of life of patients and can result in foot ulcer and amputation. The current study aimed to examine possible factors that could alter development of diabetic neuropathy.
Methods: In this case-control study, 110 diabetic patients were selected from Shariati hospital diabetes clinic. Michigan Neuropathic Diabetic Scoring (MNDS) was used to distinguish cases from controls. The neuropathic status of patients was confirmed with EMG-NCV. Multiple factors were compared between the two groups including ACE-I consumption, blood pressure, serum lipid level, sex, smoking, method of diabetes control and its quality.
Results: Statistically significant relations were found between neuropathy and age, gender, quality of glycemic control and duration of diabetes (P values: 0.04, 0.04, 0.000 and 0.005, respectively). No correlation existed between atherosclerotic risk factors (high BP, hyperlipidemia, cigarette smoking) and diabetic neuropathy.
Conclusion: In this study, hyperglycemia was the only modifiable risk factor for diabetic neuropathy. Glycemic control can decrease the incidence of neuropathy and delay its progression leading to improvement in the quality of life in diabetics. Aged and male diabetic patients and those with poor diabetes control are groups in most need of regular foot exam and more practical educations.

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Neuropathy is a common complication of diabetes mellitus. Meticulous neurological examination and electrodiagnosis are valuable tools in early diagnosis of neuropathy and prevention of its sequels.
Methods: A hundred and three randomly selected diabetic patients were recruited from the endocrine clinic. Mean age of patients was 52.6 ±14 years. 29.4% had type 1 and 70.6% had type 2 diabetes.
Medical history was taken from patients and neurological examination was done. Electroneurographic examination included nerve conduction velocity, action potential amplitude, distal latency and H reflex measurements.
Results: Neuropathy was found in 79.4% of patients. The prevalence of neuropathy had a direct relation with duration of the disease. The most common complaints were tingling and numbness of extremities (72%) and burning sensation of the feet (36%). The most common physical findings were abnormal ankle jerk (92%), and decreased vibration perception (76%) in feet. Abnormal H reflex
(92.5%) and decreased amplitude of action potentials (79%) were the most common electroneurographic findings. There was a strong correlation between clinical and electroneurographic findings.
Conclusion: Neuropathy was quite common in diabetic patients. Neurologic examination is, therefore, recommended to prevent unnecessary workups and prevent complications.

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Background: Diabetic Neuropathy is the most common and troublesome complication of Diabetes Mellitus, leading to the greatest morbidity and mortality and resulting in a huge economic burden for diabetes care. Early diagnosis of distal symmetric sensorimotor polyneuropathy, a common complication of diabetes, may decrease morbidity by allowing potential therapeutic interventions.
Methods: In 68 diabetic patients after neuropathy screening by U.K and Michigan scores, Bilateral sural nerve conduction parameters as nerve conduction velocity, latency and amplitude were determined and analysed.
Results: 54.4% of patients had Rt sural abnormal response, 50% had abnormality in left side and 39.7% had bilateral abnormality. There was significant statistical correlation between Michigan physical score and electrophysiologic finding (P-value < 0.003) but no correlation with U.K score (P-value > 0.3). The most prevalent abnormal electrophysiologic finding was amplitude decrement of sural response. Conclusion: Sural nerve response is one of the simplest and most sensitive peripheral sensory nerves for electrophysiologic study of diabetic neuropathy and its evaluation is recommended in all diabetic patients in spite of normal physical examination and history for detection of subclinical neuropathic cases. For increment of sensitivity, amplitude measurement of sensory response is highly recommended.

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Background: Foot complications are among the important problems of diabetic patients. Vascular and neurological involvements are two major causes for such complications.
Methods: We studied 142 diabetic outpatients referred to diabetes clinic of Dr.Shariati Hospital from Dec. 2003 to Sep. 2004. We performed different neurological and vascular tests to assess the diabetic foot and data were analyzed by SPSS software.
Results: 54.9% of the cases reached the symptom score of 5 and upper so they had neuropathy regarding the Michigan Neuropathy Disability Score (MNDS). By analyzing the overall symptom and sign scores, 61% had neuropathy. Regarding MNDS, 42.7% of the subjects were neuropathic. Finally 23.9% were unable to sense at least one point from 12 points of monofilament examination. 16.9% of the patients had the complaint of intermittent claudication, in 8.8% at least one of the peripheral pulses was not palpable, whereas 10.6% had some degree of PAD regarding to ABI and toe pressure.
Conclusion: Using a monofilament is the most reliable method for screening of the neuropathy in diabetic patients. On the other hand, relying on symptoms like intermittent claudication and physical examination in order to find peripheral arterial disease in diabetic patients may lead to miss many cases, thus, performing some more precise diagnostic tests, such as ABI and toe pressure are highly recommended and reliable.

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Background: Vascular factors in conjunction with metabolic issues are involved in both etiopathogenesis of diabetic neuropathy (DNU), and more remarkably in "repair" phase, when the net balance between neuroregenerative/degenerative reactions is dictated to some extent by these factors. The ischemic nature of DNU indicates the importance of re-establishment of blood vessels. VEGF, a growth factor which, in addition to its hemodynamic effects, possesses an "angiogenic" capacity has been the subject of extensive investigations in DNU, especially, interventional therapies. The impacts of racial and inherited backgrounds in the development of DNU suggest that the genetic issues partially govern the outcome of diabetic late complications, including DNU. By conducting a candidate gene case-control association study, present study explores the possibility if the inter-individual variations of VEGF gene structure by any means encode the genetic susceptibility/resistance in the course of DNU.
Methods: The distribution of VEGF gene polymorphisms frequencies were analyzed at positions –7*C/T, -1001*G/C, -1154*G/A and –2578*C/A and were evaluated by ARMS-PCR in 248 type 1 diabetic subjects (81 DNU+, 167 DNU−) and 113 healthy controls, all from "British-Caucasian" origin.
Results: When the frequency of the polymorphic alleles/genotypes between patients and controls, and also between two subgroups within patients' group with each other (DNU+ vs. DNU−) or with healthy controls were compared, only in one situation a significant difference was evident. The distribution of a VEGF gene polymorphism at promoter region (–7*C/T) at allelic (but not at genotypic) level was notably different between diabetics, with and without neuropathy, while the minor allele (T) conferred a protective effect (P=0.03 OR = 1.75).
Conclusion: The present study may imply a prognostic value for VEGF gene polymorphism at promoter region (–7*C/T) in DNU. However, it requires further studies to appreciate better the phenotypic impact of this polymorphism in this chronic complication of diabetes. A catalog of candidate genes polymorphisms that functionally reflect a protection/predisposition to DNU can provide the genotypic profile that can be useful to reasonably predict the overall behavior of diabetic subjects to the metabolic derangements relative to development of DNU, which in turn may require adoption of relevant preventive and therapeutic measures.

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Background: Neuropathy is one of the most common and dangerous complications of diabetes. Diabetic neuropathy account as the most common cause of mortality among patients. Many studies suggest that neuropathy have a negative effect on quality of life. Although there is limited evidences about relationship between diabetic neuropathy and quality of life in Iran, so this study was conducted to investigate this interaction among a group of patients.
Methods: As a descriptive-analytical study, 304 diabetic patients with neuropathy was selected via convenience sampling method. The data were collected through interview and physical examination. The tool of data collection was the information sheet of medical records and questionnaire that consisted of three parts, demographic and disease characteristics, list of neuropathic complications of diabetes and questions about dimensions of quality of life. The reliability evaluated via test-retest method and validity assessed via content validity method.
Results: the results revealed that tingling (96.1%) and pain (92.1%) in the case of sensory neuropathy were the most common complains. Sexual dysfunction (72.4%) and gastrointestinal problems (70.4%) account the most common symptoms in view of autonomic neuropathy. The results revealed that quality of life among all patients was fairly desirable and there was a significant relationship between neuropathy and quality of life (P<0.001).
Conclusion: According to the findings of this study, there is a significant relation between neuropathy and quality of life in diabetic patients. Our results suggest that nurses and educational supervisors should pay attention to promote different dimensions of quality of Life in diabetic patients with neuropathy.

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Background: Diabetic neuropathy is one of the most common complications of diabetes mellitus, which is associated with a decrease in the synthesis and transport of neurotrophins . The aim of present study was to investigate the effect of endurance training on gene expression of nerve growth factor (NGF) in the sensory spinal cord of rats with diabetic neuropathy. Methods: Twenty eight adult male Wistar rats in the body mass range of 326.3±8.4 gr, randomly assigned in to four groups: diabetic control, diabetic training, healthy control and healthy training. For inducing diabetic neuropathy, after twelve hours of food deprivation, intraperitoneal injection of STZ solution (45 mg/Kg) method was used. Two weeks after STZ injection, the endurance training protocol was performed for six weeks and Twenty four hours after the last training session, rats were sacrificed. Gene expression of NGF in rat spinal sensory segments were measured with Real time technique. In order to determine the significant differences between groups and Interaction independent variables two way anova and LSD post hoc test were used. Results: Endurance training, resulted in a significant increase in gene expression of NGF in the rats. Also, in compare with diabetic control, training led to significant decrease in blood glucose levels in diabetic training group. Conclusion: Increased physical activity and exercise can strongly affect pathological factors associated with diabetic neuropathy by increasing nerve growth factor. It is recommended that for prevention of neurological complications and treatment of diseases associated with diabets exercise training could be used as a non-pharmachological treatment.

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Background: Increased and decreased CDK5 gene expression regulation, as a protein kinase, is associated with launching death or survival pathways in the nervous system. According to the chronic effects of endurance training on growth Germination, Neuronal function and improvement of pathological conditions of neurodegenerative diseases, the aim of our study was to investigate the effect of 6 Weeks Endurance Training on Gene Expression of Cdk5 in spinal motor part of Male Wistar Rats with Diabetic Neuropathy. Methods: Twenty eight adult male Wistar rats ten year old in the weight range of 326.3±84gr, were randomly divided into four groups including healthy control (C), healthy training (HT), neuropathic control (N) and neuropathic training (NT). Diabetes was induced with one shut injection of STZ(45mg/Kg) and after confirmation of neuropathic condition with behavior tests, training groups performed 6 weeks endurance training(with moderate intensity and increasing) on the treadmill. CDK5 gene expression in Spinal motor segments forming the sciatic nerve was measured with Real time technique and calculated using the 2-ΔΔCT method. Results: After 6 weeks of endurance training, CDK5 gene expression in spinal motor part of (NT) group was significantly lower than the (NC) group, also, in comparison with neuropathy control, training led to significant decrease in blood glucose levels in neuropathic training group. Conclusion: According to the specific role of CDK5 in neuronal growth or death, our study showed the beneficial effects of Chronic endurance exercise on neural networks leading to reduced gene expression of CDK5 in a pathologic condition.

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Background: Balance dysfunction is one of the problems in diabetic patients so that peripheral neuropathy and decreased somatosensory sensitivity are the most important causes for it. One of the supposed theories for diabetic peripheral neuropathy is reduction in blood flow secondary to pathologies of peripheral neural arterioles. Intermittent Pneumatic Compression, regarding to its effect on vessels hemodynamics and perfusion improvements, has been considered in recent years. The aim of this study is to evaluate the effects of this method on improvement of neuropathy signs and symptoms improvement in patients with type 2 Diabetes and neuropathy. Also, regarding to the role of neuropathy on balance impairment, other aim of this study is to investigate the effect of this method on improvement of dynamic balance in diabetic patients. Methods: This study is a clinical trial study. 39 patients with diabetes type 2 and neuropathy divided into intervention (20 patients) and control (19 patients) groups. The intervention group underwent 10 sessions of IPC treatment, with 45 minutes for each session and one day interval between them. Neuropathy severity changes (by Valk and Michigan Questionnaires), Proprioceptive sensation (assessed by Diapason), and balance (by Biodex system), were evaluated in both groups in first and final sessions. Results: Anterior-Posterior Stability Index and Overall Stability Index obtained from Biodex system in level 6 showed significant changes. Vibration sensation, and Valk and Michigan neuropathy questionnaires also showed significant improvements (P<0.05). Conclusion: This study showed that IPC treatment method has positive effects on improvement of neuropathy severity, Vibration sensation and dynamic stability (Biodex).

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Background: Diabetic neuropathy leads to skeletal muscle atrophy however atrophy signaling mechanisms are not well documented. The aim of the present study was to investigate Sunday Driver (Syd) gene expression in soleus muscle of Wistar male rats with diabetic neuropathy. Methods: Twelve male Wistar rats were randomly assigned in 3 groups: diabetic trained, diabetic untrained and healthy control. Two weeks after STZ injection (45 mg/Kg), diabetic neuropathy was demonstrated with mechanical allodynia and thermal hyperalgesia tests and after which moderate endurance training protocol was performed for 6 weeks. 48 hours after final training session, the rats were dissected and soleus muscle tissues were removed. Also Sydgene expression was measured with Real time- PCR methods. Results: Soleus muscle weight was decreased in diabetic groups (P=0.001), but compared with diabetic untrained group, was higher in diabetic trained group (P=0.001). Sydgene expression in diabetic untrained group was higher than healthy control group (P=0.001). Also, compared with diabetic untrained group, training significantly decreased Sydgene expression and blood glucose levels in diabetic trained group. (P=0.001 and P=0.0001, respectively). Conclusion: In soleus muscle of diabetic rats, Sydm RNAup-regulation is involved in development of muscle atrophy and training as a non-pharmacotherapy strategy can modulate and get it close to normal levels. So, it is suggested that Syd should be noted as a novel treatment in diabetes disease.

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Background: Glycogen synthase kinase 3 beta is a key regulator of many signaling pathways. It is reported that Inhibition of this kinase results neuronal survival. Accordingly in this study we investigated the effect of endurance training on the gene expression of GSK-3β in the sensory areas of the spinal cord of male Wistar rats with diabetic neuropathy.

Methods: we randomly assigned 16 male Wistar rats into four groups: healthy control, healthy trained, neuropathy control, neuropathy trained. Intraperitoneal injection of a STZ (streptozotocin) solution (45 mg/kg) was used to induce diabetes. At two weeks after STZ injections, the mechanical allodynia and thermal hyperalgesia tests demonstrated the presence of diabetic neuropathy. A moderate endurance training protocol was performed for a six- week period. At 24 hours after the final training session, the rats were sacrificed and the L4-L6 sensory neurons of the spinal cord tissue were removed. GSK-3β mRNA expression was performed using real time-PCR.

Results: Statistical analysis shows that neuropathy trained experiences a decrease in gene expression in comparison to neuropathy control (P=0.02). On the other there was significant difference between healthy control and neuropathy control (P=0.02). However, there was no significant difference between healthy control and neuropathy trained.

Conclusion: we claim that endurance training will effectively decrease the expression of GSK-3β in the sensory areas of spinal cord of male Wistar rats with diabetic neuropathy. Endurance training as a non- pharmacotherapy strategy can modulate and return GSK-3β to approximate normal levels.

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Background: One of the most common complications of Diabetic Polyneuropathy (DPN) is decreased balance and Postural Control disorder. Balance has an important role in static and dynamic activities as a base of activities of daily living. The objective of this study was the evaluation and comparison of dynamic and functional balance in patients with DPN and healthy subjects.

Methods: In this study, dynamic and functional balance of 11diabetic patients with DPN (detected by Michigan questionnaire) and 11 healthy subjects were evaluated by Biodex Balance System (BBS) and Tandem Stance (TS) test in open and closed eyes conditions. The participants were matched by age and BMI. An independent t-test was used to compare balance parameters between patient and normal group. Furthermore, the correlation between dynamic balance parameters of BBS and TS tests were calculated using the Pearson’s Correlation Coefficient.

Results: The results of BBS in patients with diabetic peripheral neuropathy were significantly higher than normal subjects (P<0.05). The mean of time of TS test in diabetic group was significantly lower than healthy subjects (P<0.05). Also there was a significant (P=0.004) negative (r = 0.794) correlation between Medio-Lateral stability index (recorded from BBS) and TS with open eye, in diabetes group.

Conclusion: Older adults with DPN have an impaired functional balance in comparison with matched control subjects and this may expose the patients to danger of falling during daily activities.

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Background: Peripheral neuropathy is one of the most common problems in diabetic patients. The increased risk of Diabetic Foot Ulceration (DFU) and amputation would be a complication of diabetic neuropathy. The aim of this study was to compare the DFU healing in different severity classification of neuropathy.
Methods: This is a retrospective study that was conducted over a two-year period from April 2016 to March 2018 according to the information of patients records with Diabetes Mellitus (DM) referred to clinic of diabetes and metabolic disorders of Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences. Wound healing criteria including area, depth and healing duration were studied. Accordingly, changes in the area and depth of wounds were evaluated and reported during the first, third and sixth months after baseline. Data were analyzed using descriptive and inferential statistics using SPSS software version 16.
Results: The results of the study of patients with neuropathic ulcer showed that males and age group of 56 to 65 years had the highest frequencies. In addition, most of these patients suffered from type 2 DM (79%). The rate of wound healing, which was measured by area and depth of wound in three time periods, differed in different severity classification of neuropathy; at mild level of neuropathy the area and depth of wound decreased faster but in severe neuropathy, duration of wound healing in both mentioned criteria has increased. Regarding to the increase in the duration of DM, the healing time increased too. However the rate of wound healing decreased with increased age (p-value = 0.001).
Conclusion: Evidence suggests that early identification of neuropathy can reduce the incidence of DFU and amputation. Due to the slow healing of the size and depth of the wound in diabetic patients with severe neuropathy, it is necessary to prevent DFU by conducting preventive care and educational interventions.

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Background: Neuroinflammation and oxidative stress play a pivotal role in the diabetic neuropathic pain. The aim of this study was to evaluate the effect of aerobic exercise with melatonin on RAGE gene expression and some indicators of oxidative stress in rats with diabetic neuropathic pain
Methods: Forty 8-week-old male Wistar rats (weight range 204 ± 11.3 g) were randomly divided into five of 8 groups including: diabetic neuropathy (50 mg / kg streptozotocin intraperitoneal injection), diabetic melatonin neuropathy (mg / kg 10 melatonin daily for 6 weeks), diabetic neuropathy exercise (30 minutes of aerobic exercise at 15 meters per minute, 5 days a week for 6 weeks), diabetes melatonin neuropathy and healthy exercise and control. After confirmation of diabetic neuropathy by behavioral tests, exercise protocol and supplementation were performed. RAGE gene expression was measured by real-time technique and oxidative stress indices in spinal cord tissue by spectrophotometer. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis.
Results: Exercise and melatonin reduced the sensitivity of the nervous system to thermal hyperalgesia and mechanical allodynia. Aerobic exercise with melatonin significantly reduced RAGE gene expression and MAD concentration and increased the activity of SOD and CAT enzymes compared to the diabetic neuropathy group (P <0.05).
Conclusion: Aerobic exercise with melatonin modulates the expression of RAGE gene and oxidative stress indices and improves the sensitivity of nociceptors to pain factors. It is recommended to use aerobic exercise with melatonin for diabetics to reduce neuropathic pain.

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Background: In this study, the effect of oral administration of recombinant human interleukin-2 (rhIL-2) on brain NO level and AChE activity in hyperglycemic conditions induced by high-sucrose diet (HSD), as a type-2 diabetes model, was investigated in Drosophila melanogaster.
Methods: In this experimental research, adult fruit flies of both sexes (30 in each group) were divided into the six groups: receiving normal diet (ND); high-sucrose diet (HSD); ND with rhIL-2 at 0.01 and 0.1 ng/ml; and HSD with rhIL-2 at 0.01 and 0.1 ng/ml. Flies were bred on these culture media for three weeks. At the end of the experiments, the brains of the flies were extracted, homogenized, and glucose, NO, and AChE activity levels were measured by the kit.
Results: Glucose level, AChE activity and NO level increased in brain homogenate of HFD flies compared to ND group. The body weight of HSD flies was reduced compared to the ND. Administration of rhIL-2 along with HFD significantly prevented these changes.
Conclusion: These findings suggest that rhIL-2 partially prevents diabetic neuropathy in Drosophila. It seems that the preventive effects of this compound are mediated through mechanisms dependent on nitric oxide and acetylcholinesterase in the brain.