مجله دیابت و متابولیسم ایران
سال چهارم شماره 1 (پیاپی 7، پاییز 1383)

Due to homeostatic and regulatory potentials of nitric oxide (NO) in vascular physiology, regulatory systems that determine NO bio-synthesis and bioavailability have been the subject of extensive research in molecular medicine. In the field of vascular system pathophysiology, endothelial nitric oxide synthase (eNOS) which is the major producer and regulator of NO in vascular tissues has received the most attention. Impairment of NO bioavailability (NO quenching) is a common feature in poorly controlled diabetics due to increased catabolism and decreased production of NO. Such impairment in severe forms could end to vasodilation breakdown in peripheral tissues (mainly in skeletal muscles) and defective regional blood flow, that in turn disturb insulin-dependent glucose uptake ensuing insulin resistance state. The phenotypic impact of an eNOS gene polymorphism at position 786*C/T (that its functionality has been revealed already) on genetic propensity to diabetic retinopathy is evaluated in a British-Caucasian population with type 1 diabetes (T1DM). In contrast to genotypes, there was a significant difference in distribution of allele frequencies between T1DM patients (n= 249) and healthy controls (n= 104) (p= 0/036), that may imply eNOS and/or NO involvement in development of T1DM. Most notably a significant difference also was evident in allele frequency between retinopaths (n= 134) and healthy controls (p= 0/02). No significant difference was detected when the genotype/allele frequencies were compared between retinopaths (n= 134) and non-retinopaths diabetics (n= 115) (p=NS). Our data is compatible with previous studies which demonstrated that allele C of eNOS 786*C/T polymorphism is associated with increased HbA1c levels. By emphasizing the phenotypic and prognostic value of the abovementioned polymorphism, our data calls for further investigations to find out whether this polymorphism can be employed as a genetic marker in clinical medicine to recognize high-risk diabetics at the time of diabetes onset/diagnosis.

Type 1 diabetes (T1DM) is an organ specific auto-immune disease, which is resulted by selective destruction of  islet cells. Insulitis as the initial event prior to T1DM development is featured mainly by lymphocytic infiltration, that may recede frequently leading to healthy state (benign insulitis). Among the issues that govern which of these outcome lie ahead in insulitis are the genetic background of the host and also the immunological circumstances in islet's micro-environment. As a "case-control association study" the impact of a polymorphism within TNF-gene at position -308*G/A on genetic susceptibility to T1DM is analyzed in a British-Caucasian population (248 cases and 118 healthy controls). The distribution of genotype/allele frequencies between patients and controls did not reflect significant differences (p= NS). Since the crucial role of TNF- in development of T1DM is well established, our data may confer that the examined polymorphic marker does not have functional effects on TNF- gene expression, influencing the local or systemic level of this pro-inflammatory cytokine. However, in addition to addressing the uncertainties in "genotype-phenoype" correlations in complex diseases (i.e. T1DM), the negative results of our study also may instead draw attention to the potential impacts of post-transcriptional regulatory mechanisms relative to gene structural-based regulatory systems.

up to know many herbal medicines with different oral formulations have been recommended for diabetes. The aim of this study was to investigate the effect of 4 herbal hypoglycemic agents include garlic (Allium sativum) neem (Azadirachta indica), tulsi (Ocimum sanctum) and bitter gourd (Momordica charantia) on blood glucose, antioxidant enzymes and metal ions in diabetics Crude extracts of herbal agents was prepared and each one was given to one group of diabetic rats. Two group of diabetic rats received insulin and glibenclamide. As controls, two groups of healthy and diabetic rats received saline. Body weight, fasting blood glucose, antioxidant enzymes and metal ions were measured before and after the study. All agents including herbal preparations, insulin and glibenclamide reduced the levels of blood sugar and lipid peroxide when compared with diabetic control. These agents also increased levels of antioxidant enzymes in diabetic rats. Antioxidant enzymes decreased significantly in diabetic controls. Metal ions increased in diabetic rats treated with herbal agents, insulin and glibenclamide but decreased in diabetic controls. Above mentioned herbal plants may be useful in the treatment of diabetes as they not only have hypoglycemic effect but they also protect rats from free radical mediated cellular injury by improving the activity of antioxidant enzymes. They also improve the levels of metal ions which are associated with antioxidant enzymes.

Recurrent GDM are more common in women with previous GDM. Also GDM is an important risk factor for abnormal glucose tolerance and type 2 diabetes during postpartum. This study aims to determine the prevalence of postpartum IGT and T2DM in women with previous GDM.

A cohort study was conducted on 2416 pregnant women referred to five Tehran university hospital clinics. The universal screening was performed with a GCT-50g and those with plasma glucose level130mg/dl, were diagnosed as having GDM if they had an impaired GTT-100g based on Carpenter and Coustan criteria. All pregnancies were followed up until delivery. Available GDM patients underwent an OGTT-75gr within 6 to 12 weeks after delivery. Postpartum diabetes mellitus was diagnosed according to ADA criteria. Student T test and ANOVA used for comparing means of variables and Chi Square used for comparing of frequency of variables. Value of P less than 0.5 determine as significant different.

the prevalence of GDM was 4.7%. In fallow up 85.9% of women with GDM were screen in postpartum. 16.3% of women required insulin treatment and other patients were managed with diet. Prevalence of postpartum diabetes mellitus and IGT were 8.1% (CI 95%: 3.5-15.4) and 21.4% (CI 95%: 13.7-30.8) respectively, and 70.5% returned to normoglycemy.

Abnormal glucose tolerance is a common disorder in the early postpartum in GDM patients. Because of the high incidence of glucose tolerance disorders in women with previous GDM, screening, diagnosis and management during pregnancy was important for prevention of these disorders. Following up these mothers after delivery is highly recommended.

Currently different criteria are used to diagnose Gestational Diabetes. ACOG (American college of obstetric and Gynecology) accepted NDDG's (criteria National Diabetes Data Group) Criteria and ADA (American Diabetes Association) accepted Carpenter Caustan’s. Although both of these criteria have been achieved by O Salivan and Mahan’s reaserches, the number of patients has been diagnosed are different. The aim of this study was to compare Gestational Diabetes prevalence according to Carpenter Caustan’s and NDDG’s Criteria. 1200 pregnant women were screened in a prenatal care clinic. Patients with definite diabetes were excluded. According to universal GDM screening method, for all of the patients GCT and GTT (if GCT > 130) were preformed. The results evaluated according to Carpenter Caustan’s and NDDG’s criteria. In this screening, 377 participants had positive GCT, according to Carpenter and Caustan’s criteria 83 women (6.9%), and according to NDDG criteria 50 women (3.6%) had Gestational Diabetes Mellitus. If the cut of point of GCT was 140 mg/dl instead of 130 mg/dl, according to Carpenter and Caustan’s criteria 16 women (18.1%), and according to NDDG 4 patients (9%) were missed. Regarding the significant difference between two methods in diagnosis of gestational diabetes mellitus, assessment of each method value in improving prognosis and outcomes is necessary. According to the results the cut of point of 130mg/dl, as recommended in previous studies, has more accuracy for screening.

Type 2 diabetes is a hereditary disease but the inheritance and responsible genes have not been clearly clarified yet. According to the most studies, diabetes is one of the most common causes of mortality and morbidity in populations. Diabetes occurs in 30% of first degree family members of diabetic patients, But most people are not aware of their disease. We studied first degree relatives of type 2 diabetes and screened them for diabetes, IFG and IGT.174 families(1556 people) of Tabriz residents were studied, among them 1232 persons grater than 30 years were alive and FBS and OGTT were done in this group. According to this study, 1232 persons were alive and 324 persons had died and DM was found in 343 (27.9%) and 82 (25.3%) of them respectively. We found 179 (14.5%) persons with IFG and 89 (7.2%) with IGT.The percent of diabetes in offspring and siblings were 32.9% and 22.1% respectively. The majority of patients had 41 – 50 years old. Risk of diabetes among offspring who had diabetes in both parents was more than the ones who had diabetic father or mother. In this study, women with diabetes were more than men (32.4% vs. 22.2% respectively). The prevalence of Diabetes type 2 in first-degree relatives was more frequent between sister and brother (41.95%), followed by that between father and son (10.9%). Prevalence of diabetes in most populations is 8 – 10 %. If diabetes occurs in someone, risk of development of diabetes will increase to 30% in their family members. Therefore, screening must be done in all family members of diabetic patients to recognize the problem and to prevent from diabetes complication.

Gliclazide is a second generation sulfonylurea which its efficacy and safety in the treatment of diabetes has been established. Diamicron MR (30 mg) is a new formulation of gliclazide with modified release which offer once daily dosage administration. This study was designed to assess the effect of combination therapy with diamicron and metformin in the treatment of type 2 diabetes. 16 patients with type 2 diabetes (2 males, 14 females) more than 35 years old who despite treatment with glibenclamide and metformin had poor diabetes control participated in this clinical trial.HbA1c, lipid profile, liver and renal function tests at the end of study were compared with before. No significant changes was found in FBS, BS2hpp, lipid profile and renal and liver function tests at the end of study. Patient's weight was stable during the study. Regardless of well efficacy of diamicron in the treatment of new diabetics cases, it is not recommended for patients with poor diabetes control despite of combination therapy with metformin and glibenclamide.

Diabetes type 1 is an autoimmune disease that is associated with other autoimmune disorders like Hashimoto thyroiditis. The purpose of this study was to determine the prevalence of autoimmune thyroid disease (ATD) in type 1 diabetic patients in the south of Iran (Bandar Abbas). A cross-sectional study, was conducted 48 type 1 diabetics and 41 age and sex matched healthy controls were evaluated for the presence of ATD. Blood sample were collected from all of the subjects for the measurement of thyroid autoantobodies [anti thyroid peroxidase (anti-TPO) and anti thyroglobulin (anti-TG)], T3, T4, TSH, RT3U and HbA1c. Prevalence of positive anti-TPO and anti-TG was 29 % and 29% respectively in diabetic patients and 2% and 7% respectively in control group (P<0.05). The prevalence of ATD (positive anti TPO or anti TG) in diabetic patients and control subjects was 35% and 7% respectively (P<0.05). The prevalence of positive anti TPO and anti TG was higher in girls. There was no association between the prevalence of positive autoantibody and duration or age of onset of diabetes. 17.6% of diabetic patients with positive autoantibody had thyroid dysfunction (subclinical hypothyroidism and hyperthyroidism). Regarding high prevalence of ATD in type 1 diabetic patients in Bandar Abbas (approximately 1 out of 3 patients), screening for ATD and thyroid dysfunction is recommended for all type 1 diabetic patiens and in those with positive autoantibody consecutively.

Cardiovascular disease is one of the major leading cause of death in Iran. There is a strong association between parental history of cardiovascular disease clustering of risk factors in the offspring. Detection and treatment of cardiovascular risk factors since childhood is essential to reduce the incidence of disease in adulthood. This study was performed to identify major cardiovascular risk factors in middle school-aged children and their parents in high risk compared to control families. The middle schools of the 6th of Tehran were divided randomly into two groups. A total of 169 high-risk children with their families were recruited from the first group while 105 control children with their families were recruited from the second group of schools. Coronary risk factor survey was performed in the participants. Prevalence of increased total- and LDL-cholesterol and high FBS were higher in high-risk parents and children. Prevalence of increased BMI was higher in fathers and children of high-risk families. More fathers in high-risk families were smoker. The means of waist circumference and WHR were significantly higher in high-risk fathers. The means of total- and LDL- cholesterol were significantly higher both in parents and children of high-risk group. The means of FBS were significantly higher in fathers and offspring of high-risk families. Cardiovascular risk factors are more prevalent and clustered in high-risk families. Screening of these families is essential to prevent progression of cardiovascular disease since childhood and reduce its burden in adulthood.

During extrinsic coagulation pathway, a complex is developed between factor VII, calcium and tissue factor (a cell membrane lipoprotein that is exposed after cell injury). Factor VII needs calcium and vitamin K for its biologic activation. Coronary artery disease can be induced by increased level and activity of the coagulation factors VII, VIII and IX. In postmenopausal period, estrogen can decrease blood lipids and thereby decreases risk of coronary artery disease. However, the exact effects of the estrogen on the other predisposing factors of the coronary artery diseases are unknown. Our objective in this study was to evaluate the effects of oral hormone therapy regimen on fibrinogen and other coagulation factors. 60 menopause women with history of hysterectomy were randomly allocated in 2 groups. One group was treated with conjugated estrogen 0.625mg/day and the other group was treated with conjugated estrogen 0.625mg/day and medroxy progesterone 2.5mg/day. Serum fibrinogen level and activity of coagulation factors VII, VIII and IX and blood lipids level were checked before and 3 months after treatment. In the estrogen alone treated group, mean of factor VII activity showed significant elevation 3 months after treatment as compared with prior to hormone therapy(p<0.05). There were no significant changes in means of coagulation factors VIII, IX activities and serum fibrinogen level in estrogen  medroxy progesterone treated patients before and after treatment (p>0.05). In both groups, honi1one therapy significantly decreased serum cholesterol level and LDL-C and increased HDL-C (p>0.00) but the serum triglyceride level was increased in the estrogen alone treated group. Significant elevation of coagulation factors VII with significant elevation of serum triglyceride in estrogen treated patients is explainable. This study confirms that hormone therapy with this protocol does not change serum fibrinogen mean and activity of coagulation factor VIII and IX. This finding may be real or may be related to inadequacy of samples regarding the wide normal range of coagulation factors and serum fibrinogen. Studies with more prolonged follow-up or more samples are suggested.

Obesity is associated with many metabolic and cardiovascular diseases, for example, a direct and indirect relation has been established between obesity and diabetes, dyslipidemia, hypertension and atherosclerosis. But whether regional fat distribution contributes independently to risk remained unclear. This study was designed to determine relation between central obesity and acute myocardial infarction (AMI). In this case-control study, body mass index (BMI) and waist to hip ratio (WHR) were calculated in 420 participants (140 cases and 280 controls). BMI and WHR means were evaluated in subgroups according to age, sex and cardiac risk factors. Odds ratio (95% CI) of the MI incidence in obese participants (BMI≥27 and/or WHR≥0.85) were compared with non obese subjects in each subgroups. Mean BMI mean in the case group (27.9±4.9) was more than control group (25.8±4.9) P≤0.05). The obese individuals had more chance of AMI (OR=3.2; CI=3-3.3). This chance increased with central obesity (OR=3.4; CI=3.2-3.6). Risk of AMI in younger obese participants (OR=4.3; CI=2.8-6.8) was more frequent than older ones (OR=2.1; CI=1.7-2.4). Central obesity increased risk of AMI in women (OR=3.6; CI=3.1-4.4) more than men (OR=2.2; CI=1.7-2.5).The excess risk of AMI in obese participants in associated with major cardiac risk factors was as following: hypertension (OR=18.4; CI=9.8-22.1), diabetes (OR=9; CI=4.2-14.1), hyperlipidemia (OR=6; CI=2.1-8.4), positive familial history (OR=2.6; CI=2.1-3.4) and smoking (OR=1.2; CI=0.9-1.7). There is a strong association between BMI, WHR and risk of AMI. Central obesity comparing with general obesity has stronger relation with AMI incidence especially in women and younger subjects. In addition, cardiac risk factors except smoking aggravated correlation between obesity and AMI.

Hypertension and dyslipidemia are common in patients with type 2 diabetes mellitus. The high prevalence of cardiovascular disease in diabetic patients is, in part, related to these two risk factors. This study was performed to determine the prevalence of hypertension and dyslipidemia in newly diagnosed patients with type 2 diabetes mellitus in Isfahan. In this cross – sectional study during 2001 – 2003, 310 newly diagnosed type 2 diabetic patients, in Isfahan endocrine and metabolism research center, were studied. Height, weight, blood pressure, Plasma lipid and lipoproteins, and HbA1c were determined for all subjects. Mean age at presentation was 489.83 years, and mean BMI was 28.44.62 Kg/m2. Hypertension was present in 32.9%, hypercholesterolaemia in 61.3%, hypertriglyceridaemia in 61.6%, high LDL in 77.3%, and low HDL in 67.8% of these patietns. The mean systolic and diastolic blood pressure were 119.0816.59 and 70.0214.02mmHg, respectively. The mean for total cholestrol was 216.1043.65, for triglyceride 207.46105.67, for LDL 124.7331.45, and for HDL 43.119.29 mg/dl. Hypertension and dyslipidemia are common in newly diagnosed type 2 diabetic patients. This fact demonstrates the importance of early interventions for proper diagnosis and treatment of these two risk factors in diabetic patients.