Iranian Journal of

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Background: Metformin is used in treatment of non-insulin-dependent diabetes mellitus (NIDDM). The present study was aimed to study the pharmacokinetic and pharmaco-dynamic of metformin 500 mg tablet in healthy volunteers.
Methods: The test and reference metformin hydrochloride 500 mg tablets were administered to 12 healthy volunteers in a cross-over study. Metformin serum concentration and decrease in blood sugar levels (dBSL) were used for study of pharmacokinetic and pharmacodynamic.
Results: There was no correlation between phramacodynamic and pharmacokinetic para-meters. Also there was no increase in dBSL-(AUC0-12) with increase metformin serum concentration-time. The results of our study show that both products could be bioequivalent according to serum concentration and not blood sugar data.
Conclusion: There was no concentration – effect (dBSL) correlation for both products. Metformin didn’t decrease the blood glucose in healthy volunteers. In some volunteers there was no increase in blood sugar after meal and dextrose 20% oral solution administration which could be related to decreased absorption of glucose from gastrointestinal tract caused by metformin.

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Basic sciences attract specific attention of medical professionals worldwide. Medical genetics can bridge between clinical observations and basic sciences via specific focus on the molecular aspects of diseases. Importance of genetic counseling as the main part of management of inherited disorders should be realized by all physicians. This paper provides genetic counseling essentials with main focus on the endocrinopathies and metabolic disorders especially diabetes mellitus and its complications. This paper may help the endocrinologists to have more attention on these rules for referring rare familial or syndrome cases. High ethnicity variations and high rate of consanguineous marriage in Iran as well as increase in the incidence and prevalence of such disorders highlight the importance of molecular studies of such disorders in our country.

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 Background: Microalbominuria (MA) is early presentation of renal damage which acts as an independent factor of cardiovascular events in these patients. There are various methods for sampling and also different laboratory tests to measuring albominuria. The aim of this study was to compare of different urine collection methods for measuring albominuria using immunoturbidometry assay which has acceptable accuracy and sensitivity after HPLC (High Performance Lipid Chromathography).

Methods: Forty seven diabetic patients were selected for a cross-sectional study in 2006. For all patients 24-h urine sample were collected, also an overnight urine sample (8 hour long) and spot urine sample (morning time) was provided in the next day. The level of albumin in all samples were measured via immunoturbidometry assay. Then the results of agreement coefficient were accounted and comprised with each others.

Results: In this study 47 patients were selected which 46 of them were type 2 and one of them type 1 diabetic. Our results revealed significant correlation between all methods. In addition agreement coefficient (kappa) was accounted for all methods, time 24-h urine in comparison with 8 hours overnight urine, timed 24-h urine in comparison with spot urine and overnight urine samples in comparison with spot urine which were 0.876, 0.936 and 0.807 respectively.

Conclusion: Regarding significant agreement for screening of microalbominuria between different collecting methods, we suggest 8-h overnight or spot urine sampling carry out instead of 24-h urine collection.

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Background: Cardiovascular disease including hypertension are complications of long-standing diabetes. A few Studies had shown the positive effects of L-carnitine on hypertension. In this study, the possible effects of L-carnitne on nitric oxide (NO) levels and angiotensin-converting enzyme (ACE) activity in serum as well as systolic blood pressure (SBP) in diabetic and normal rats were studied.

Methods: In this study forty rats were used in four groups including non-treated control (C), L-carnitne treated control (CT), diabetic (D) and L-carnitne treated diabetic (DT). Diabetes was induced in rats by injection of stereptozotosin. Both of C & D groups had a free access to food and water and CT & DT groups were received daily dose of L-carnation in drinking water. At the end of 12 weeks SBP, serum NO and ACE activity were measured.

Results: Systolic blood pressure was significantly decreased in DT group compared to D group. Serum ACE activity was also significantly decreased in DT group compared to D group and the serum NO levels were significantly increased in DT & CT groups compared to D & C groups respectively.

Conclusion: Finally it could be concluded that L-carnitine may reduce SBP in diabetic rats via elevation of serum NO levels and reduction of serum ACE activity.

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Background: Leptin is a peptide strongly correlated with adiposity and is a potential determinant of obesity and its complications. The aim of this study was to evaluate the correlation between serum leptin levels and different anthropometric indices among obese women.

Methods: This analytical descriptive study consisted of 106 women with different grade of obesity (BMI ³ 25 kg/m²) and 38 women with normal weight (BMI ≤ 25 kg/m²).serum leptin and glucose levels were measured via enzyme immunoassay and glucose oxidase methods respectively.

Results: The mean (± SE) serum leptin concentrations  in apparently healthy women with normal weight ,overweight, obese grade I, and obese grade II were 6.88 ± 0.56, 39.30 ± 1.73, 46.60 ±1.04, and 48.22± 3.31 ng/ml respectively. There was a dramatic increase in serum Leptin concentration when the BMI was increased. There was statistically significant differences between all groups in serum leptin concentration (P<0.001). There was a direct and significant correlation between serum leptin concentration and BMI in obese subjects (r= 0.736, P< 0.001). There was no significant correlation between leptin with age, and leptin with WHR neither in normal weight group nor in different grades of obesity groups.

 Conclusion: Our findings showed that the serum leptin levels continuously raised with increasing degree of obesity and among different anthropometric indices serum leptin concentration has significant correlation with BMI. 

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Background: Atherosclerosis is the leading cause of mortality in the developed and some developing countries. Some people believe that opium abuse has beneficial effects for reducing blood lipids and atherosclerosis prevention. In this study, the effect of oral opium addiction on lipid profile and atherogenesis in normal and hypercholesterolemic rabbits was studied.

Methods: Thirty two male Newzeland White rabbits were used in this study. They were divided into four groups including control, hypercholesterolemic, addicted, and hypercholesterolemic addicted and were studied for three months. The blood samples were obtained and lipid profile was determined at the beginning of the study and at the end of every month thereafter. After 90 days aorta was removed to assess for lesion formation.

Results: The levels of cholesterol, triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), and atherogenic index (total cholesterol/HDL-C) in the hypercholesterolemic and hypercholesterolemic addicted rabbits were increased significantly (P<0.001). These increases in lipids and aorta lesion areas were higher in hypercholesterolemic addicted group than hypercholesterolemic group.

Conclusion: These findings suggest that oral opium abuse affects cholesterol metabolism and depending on the dietary condition can have an aggravating effect on atherosclerosis. The protective effect of morphine on cardiac disease is not probably through the modulation of lipid metabolism.

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Background: Pump therapy (CSII) is offered as a safe and effective treatment for patients with type 1 Diabetes. We examined the efficacy and safety of continuous subcutaneous Insulin Infusion Therapy for six months as a before-after clinical trial study among type 1 diabetic patients. This is the first survey of this experience in Iranian patients.

Methods: We recruited, type 1 diabetic patients without chronic complications of diabetes (retinopathy, nephropathy and etc.) and followed them for six months as a before-after clinical study with use of the pump. The efficacy of this way was assessed with HbA₁C and fasting blood sugar measurements. Safety was estimated by frequency of clinical hypoglycemia episodes.

Results: Our patients were 7 men and 2 women aged 15 - 39 years with past history of diabetes by ranging from 0.1 to 15 years. Mean level of HbA₁C at the beginning of study and after six months follow-up were %8.6 and %7.1, respectively, with significant statistically difference between them (P= 0.02). During pump therapy the mean dose of insulin were decreased to 10 units with statistically significant difference to before investigation (P = 0.03). No case of hypoglycemia and weight loss was seen. One patient had 4 kg weight gain without any significant statistical effect.

Conclusion: It seems CSII Therapy in Iranian patients with type 1 Diabetes mellitus was effective and safe. We can not conclude about possible side effects of pump based on this study.

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Background: The oxidative modification of low density lipoprotein (LDL) may play an important role in atherogenesis. Mechanism of LDL oxidation and factors that determine its susceptibility to oxidation is unknown. Copper is account as an attributing factor in LDL oxidation atherosclerotic lesions. The binding of copper ions to LDL is usually thought to be a prerequisite for LDL oxidation by copper. The aim of study was to  investigate the effect of  Naringin and Quercetin on copper bound to LDL and furthermore effect of this binding on the susceptibility of LDL to oxidative modification.

Methods: LDL was isolated from EDTA-plasma by ultracentrifugation using a discontinuous gradient. The oxidizability of LDL was measured by thiobarbitoric acid reactive substances (TBARS) after addition of CuSO₄ in absence and/or presence of Naringin and Quercetin. Finally effect of Naringin and Quercetin on formation of LDL-copper complex was studied by gel filtration.

Results: This study showed that Naringin suppresses formation of TBARS and LDL-copper complex, whereas Quercetin enhances formation of TBARS and LDL-copper complex.

Conclusion: Results revealed that Naringin with inhibition of binding of Copper to LDL may decrease the susceptibility of LDL oxidation in counter to this ion and thus may have a role in prevention of atherosclerosis. But Quercetin with stimulation of binding of copper to LDL may increase the susceptibility of LDL oxidation to this ion and thus may have a role in progression atherosclerosis.   

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Background: Resistin, an adipocyte secreted factor, has been suggested to link obesity with type 2 diabetes and insulin resistance in rodent models but its relevance to human diabetes remains uncertain. The aim of this study was to investigate the relationship between serum resistin concentrations with insulin resistance and obesity indices in type 2 diabetes and non-diabetic obese subjects.

Methods: As a case- control study 35 obese subjects with type 2 diabetes (age, 44.60 ± 6.39yr BMI, 34.23±3.92 kg/m2) and 35 obese non-diabetics (age, 43.14±9.13yr BMI, 35.54 ± 4.07 kg/m2) are recruited. Fasting lipid profile was measured by enzymatic methods. NycoCard HbA1c Kit was used to measure HbA1c.The Serum resistin, insulin and glucose levels were measured by an enzyme immunoassay using a commercially available kit and glucose oxidase methods respectively. The insulin resistance index was calculated from fasting glucose and insulin by the homeostasis model assessment (HOMA-IR) formula.

Results: The mean of insulin resistance index (HOMA-IR), HbA1c, diastolic blood pressure, triglyceride and fasting glucose in diabetics were significantly higher than non-diabetics subjects (P<0.05). Serum resistin concentrations were not different between diabetics and non-diabetics obese subjects but were significantly higher in women as compared to men (8.15±4.40 vs. 5.97±2.31 in non-diabetic) and (7.46±3.98 vs. 5.51±3.98 in diabetic) in both groups. Serum resistin was not significantly related to variables measured in both groups. In control group only, we observed a significant and negative correlation between diastolic blood pressure and resistin (r = -0.381 P = 0.024).

Conclusion: Serum resistin concentrations were not significantly different between type 2 diabetes and non-diabetic obese subjects and resistin is unlikely to be a major link between obesity and diabetes in humans.

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Background: Glucose metabolism impairment may occur during some pregnancies especially of advanced age and history of previous gestational diabetes and may result in hazardous consequences both for mother and neonate.

Methods: The present study as a case-control was conducted on 420 referred pregnant women to Shiraz hospitals that involve 70 diabetic patients and 350 non-diabetic women. Data analyzed by analysis of variance and χ square for univariate and logistic regression for multivariate analysis.

Results: From 70 diabetic patients 22(31.4%) afflicted with overt diabetes as well as 48 (68.6%) gestational diabetes. Gestational diabetes history (OR=23.14), hydramnious (OR=13.26), glucosuria at 3^rd trimester (OR=11.49), family history of diabetes (OR=4.09) and age (OR=1.03) were the most important risk factors for gestational diabetes, respectively. History of macrosomia in previous pregnancies (OR=18.83) and history of previous cesarean section (OR=11.96) were the most important predictors for overt diabetes.

Conclusion: In view of several threatening consequences of diabetes during pregnancy, screening for diabetes especially in mothers with gestational diabetes history and family history of diabetes is essential in order to control and prevention of these outcomes in mother and neonate.

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Background: High prevalence of consanguineous marriages has been reported in Iran. Since this pattern of marriage may increase the prevalence of diseases with autosomal recessive pattern of expression, the study was assigned to determine this among patients referred to diabetes and osteoporosis clinics of Dr Shariati hospital, Tehran, Iran.   

Methods: The consanguineous marriage was studied among 1789 couples of three successive generations via Questionnaire.

Results: The prevalence of consanguineous marriages in three successive generations was 9%, 17% and 19%, respectively with an increasing pattern of prevalence. Overall the prevalence of first cousins marriage was 10% with 69% among consanguineous marriage group. The higher the level of education, the lower the prevalence of consanguineous marriage.

Conclusion: In view of the increasing prevalence of consanguineous marriage that may be followed by some trouble consequences about disease expression, it seems necessary to provide facilities for genetic counseling before marriage for youth.

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Background: Type 2 diabetes mellitus is the most common type of diabetes which is triggered by various factors such as obesity, hyperlipidemia, hypertension, dietary habits and inheritance. With respect to geographic variation of diabetes prevalence, it is important to know the risk factors regionally.

Methods: As a case-control study, we looked for important risk factors of diabetes in our region. This study consisted of 400 individuals in case group and 400 individuals in control group. All these anthropometric measurements were calculated by standard methods. Blood samples taken from two groups were studied for TG, FBS, Cholesterol and HbA1c. Data are reported as the Mean±SD. P<0.05 was considered as statistically significant.

Results: There was no significant difference between two groups about mean age and sex ratio. Statistically significant difference were found for central obesity, hyperlipidemia, hypertension, polycystic ovarian syndrome (PCOS) and positive family history of diabetes in both groups (P<0.05).

Conclusion: The results showed that central obesity, hyperlipidemia, hypertension, PCOS and positive family history of diabetes are important risk factors of diabetes mellitus in Shiraz. In concordance with the results of this study, screening programme for that risk factor of diabetes in this region is suggested.

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Background: Adiponectin is an adipose tissue-derived hormone that low levels of this hormone are associated with obesity, insulin resistance, and type 2 diabetes. The aim of this study was to compare the serum levels of adiponectin in diabetic and non-diabetic obese individuals.

Methods: As a cross-sectional study 35 obese individuals with type 2 diabetes mellitus and 35 non-diabetic obese subjects were enrolled. Two groups were matched for age, gender and body mass index. Fasting lipid profile was measured via the enzymatic methods. The NycoCard HbA1c Kit was used to measure HbA1c.The Serum Adiponectin, insulin and glucose levels were measured via an enzyme immunoassay, using a commercially available kit and glucose oxidase methods, respectively. The HOMA and QUICKI indices were used to determine insulin resistance and insulin sensitivity, respectively.

Results: The mean of insulin resistance index (HOMA-IR), HbA1c, diastolic blood pressure, triglyceride and fasting glucose in diabetes were significantly higher than non-diabetics (P<0.05). The serum Adiponectin levels was significantly lower in diabetes than non-diabetics (15.74±6.70 vs. 21.52 ± 9.35) and was significantly higher in women than men (19.38 ± 7.33 vs. 12.68 ± 4.28) among diabetic and (24.63 ± 10.52 vs. 17.83 ± 6.21) among non-diabetics groups.

Conclusion: type 2 diabetes mellitus is associated with low serum adiponectin concentrations and probably adiponectin involved in the pathophysiology linking obesity to type 2 diabetes.

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Background: The relationship between diabetes and serum insulin and Zinc (Zn) levels is complex with no clear cause and effect relationships. Since Zn plays a clear role in the synthesis, storage and secretion of insulin as well as conformational integrity of insulin in the hexametric form, the decreased Zn, which affects the ability of the islet cell to produce and secrete insulin, might then compound the problem, particularly in type 2 diabetes. The aim of this study was to determine the changes of plasma Zn in patients with type 2 diabetes mellitus and healthy control in Shiraz city.
Methods: As a case-control study, we determined the serum Zn levels by atomic absorption spectrophotometer, blood HbA1c levels with columnar chromatographic method and Glucose, by enzymatic colorimetric method in auto analyzer. Data are reported as the Mean±SD and P<0.05 was considered as statistically significant Results: Results of this study revealed that levels of Zn in serum of diabetic patients is lower than in the healthy control in Shiraz city (P<0.05).
Conclusion: With respect to the result of this study, dietary educations about consuming enriched Zn foods such as sea foods and corn in diabetic patients is necessitated.

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Assessing of outcomes and risk factors in the form of qualitative variables is common in the most of medical studies and the research objectives are defined as the relationship between these variables. This paper introduces the concepts and basic and applied statistical tests to examine the relationship between these variables in these studies, including chi-square tests. Principles and method of calculating the statistics and hypothesis testing to assess the relationship between qualitative variables (or difference in proportions between groups), were presented taking into account relevant considerations. The method of reporting findings were introduced in the context of contingency tables, for all types of chi-square tests. To investigate the relationship between two binary or multi-category qualitative variables, Pearson chi-square test (in the case of establishing Cochran conditions), Yates continuity correction for small samples, in the case of not establishing Cochran conditions exact P-Value calculated on the basis of exact tests, trend chi-square test for ordinal qualitative variables and McNemar chi-square test for related samples should be used. In addition for tables larger than 2 × 2, when the overall relationship was significant, post hoc tests with appropriate correction is required. In each of these situations, examples based on research, calculations of tests were performed and their results were presented. To investigate the relationship between a set of risk factors and nominal or ordinal qualitative variables, the introduced analyses are recommended considering the situation and purpose of the proposed study.

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Background: Patient education as an integral aspect of communication between health care providers and patients plays an important role in patient health management Teach Back (TB) is a method of interactive education. Using the teach-back technique not only improves patient’s knowledge and understanding, but also increases patient’s adherence to disease management. Furthermore, self-care education to diabetic patients has always been a key strategy for successful control of diabetes. The aim of this study is assessment the effect of self care education based on Teach Back method on promotion of self care behaviors in type II diabetic patients of Hamadan city, 2012. Methods: This interventional quasi-experimental study was performed by choosing 70 type II diabetic patients Random permutation divided into two experimental (n=35) and control (n=35) groups. Educational programs base on TB designed for patients in the intervention group included four sessions. Before and one month after the educational intervention, the results were evaluated. Participants responded to the knowledge and SDSCA questionnaires. Information was collected through interviews and self report, and then data were analyzed by SPSS-20. Results: The results indicated a positive impact of TB on knowledge (p< 0.001) and self-care behaviores (p<0.001) among patients of the intervention group. Conclusion: The results showed the positive effect of education program based on Teach Back method to increase self management among diabetic patients, while implementing such programs seem to be effective in the treatment and prevention of diabetes complications.

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The P-Value cannot present a complete measure of association in medical studies considering the association between categorical variables. In such situations, measures are required to reveal the clinical importance of relation along with their statistical significance, as the effect size. This paper aims to introduce the measures of associations for categorical variables and inferences about them in these studies. Principles and method of calculating measures of associations and inference about them including confidence interval and hypothesis testing were presented to assess the relationship between qualitative variables for all types of medical studies taking into account relevant considerations. Additionaly, the method of reporting of findings were introduced in the context of contingency tables. To investigate the relationship between two binary qualitative variables, should be used the Odds Ratio in cross-sectional or case-control studies, the relative risk in cohort studies, and prevalence ratio in cross-sectional studies and risk difference in all type of studies along with their confidence intervals and/or their significance tests considering the independent or related groups of studies. Additionally, for bigger than 2 by 2 tables, the method of calculating of above mentioned measures considering a reference category and other measures such as Phi, Crammers V, contingency and uncertainty coefficients , Lambda, Gamma, Summers D, Kendals tau-b and tau-c would be recommended. In each of these situations, based on research based examples, calculations of tests were performed and their results were presented. To investigate the relationship between a set of risk factors and binary and multi-category qualitative variables, the introduced analyses are recommended considering the situation and purpose of the proposed study.

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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: CoQ10 is a lipid-soluble and a powerful antioxidant. Decreased level of this antioxidant was reported in many conditions like vascular, diabetes, high blood pressure and coronary artery diseases. With regards to increased oxidative stress in diabetes and its role in the development of high blood pressure, this study aimed to examine the effect of Q10 supplementation on blood pressure level and its relation to nitric oxide metabolites (NOx) level in type 2 diabetic patients. Methods: In this 12-week randomized controlled trial, T2D subjects received either placebo or coenzyme Q10 (100 mg twice a day). Anthropometric measures, blood pressure, biochemical analysis including NOx level, fasting blood glucose, glycosylated hemoglobin (HbA1c) and lipid profile were evaluated at the beginning and after the intervention. Results: The intervention resulted in a significant improvement in systolic blood pressure (115.3±27.61 versus 118.2±12.6 mmHg), diastolic blood pressure (77.1±8.22 versus 80.3±12.11mmHg), NOx (Pvalue=0.014) and HbA1c. Moreover Q10 supplementation resulted a significant decrease in elevated levels of cholesterol. Conclusions: In conclusion, CoQ10 supplementation (200 mg/day) for 12 weeks, significantly decreased systolic and diastolic blood pressure, NOx, HbA1c, total cholesterol and LDL-C in type 2 diabetic patients.

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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.