مجله دیابت و متابولیسم ایران
سال پنجم شماره 3 (پیاپی 16، بهار 1385)

Diabetes is a common endocrine disease in human kind. In most type II diabetic patients, obesity and overweight status account as the serious health problems worldwide and variety of endocrine factors well known that have regulatory role in weight balance and body composition including Leptin and IGF-I factor. The aim of this study was to examine the correlation between Leptin and IGF-I in type II diabetics and controls. As a case- control study, 38 type 2 diabetics (20 males and 18 female with mean age 49.22) and 46 healthy controls (16 males and 30 females with mean age 49.52) are recruited. We measured the concentrations of FPG, IGF-I, HbA1C and IGFBP-3 in both groups. FPG was measured by enzymatic glucose oxidase method and Hb Gold analyzer HPLC was used to measure HbA1C. Determination of Leptin, IGF-I, IGFBP-3 and Insulin concentrations were carried out using ELIZA method. P< 0.05 was considered as statistically significant. The mean of BMI and age were not significantly different in both groups. The mean serum levels of IGF-I, Leptin, Insulin, FPG and HbA1c concentrations in type II diabetics were significantly higher than controls (P< 0.05). In males, the mean serum levels of Leptin were statistically lower than in females in both groups. There was a strong correlation between IGF-I and IGFBP-3, Leptin and insulin, IGF-I and age, and BMI with FPG in both patients and controls (P< 0.05). A reverse correlation was observed between IGF-I and HbA1c in patients and controls (P< 0.05). It is speculated that based on this findings, Leptin and IGF-I system could have regulatory roles in body composition and fat content particularly in obese and overweight diabetic patients and have significant correlation with Insulin, glucose, BMI and age.

VEGF is newly discovered growth factor that has diverse biologic properties. The bottom-line of these activities is conduction and orchestration of a series of reactions that are taking place at microvasculature of different tissues/organs. Among the growth factors, cytokines and other mediators that reflect meaningful alteration in their local/systemic level, VEGF is the distinct player which can explain by its own all hemodynamic and architectural manifestations present in diabetic retinopathy (DR). The present study was conducted to pursue the role of a candidate gene structure variation, VEGF gene polymorphisms, in genetic susceptibility/resistance to development of DR through a cross sectional case-control study. The frequency of four SNPs in VEGF gene at positions –7*C/T, –1001*G/C, –1154*G/A and –2578*C/A has been traced among 248 type 1 diabetic subjects (135 DR+, 113 DR−) along with 95 healthy controls. The populations had "British-Caucasian" background and ARMS-PCR technique was employed for DNA genotyping. Comparing the polymorphic variant's frequency at both allelic and genotypic levels among different groups/subgroups, significant difference was noticeable for –7*C/T polymorphism between diabetic patients with vs. without DR, while T allele conferred protective effect (p=0.002; OR=1.98). Contemplating that up-regulation/over-expression of VEGF (local/systemic) as a common pre-requisite for DR development, our hypothesis was that whether the VEGF gene structural variations is correlated with the magnitude of VEGF expression in response to different stimuli present in diabetic context, namely hypoxia and hyperglycemia. Our data indicate that among the examined polymorphisms of VEGF gene, only SNP at position –7*C/T harbored significant difference between DR+ vs. DR− cases, proposing phenotypic impact for that SNP illustrating by evolvement/impediment of DR. However, reminding the insubstantial role of genetic issues in development of DR relative to DN or DNU, replicating current hypothesis by providing larger sample size and also employing more polymorphic markers could shed more light on the subject of present study.

Uncoupling protein-2 (UCP2), one of the mitochondrial transporter memborane protiens, is suggested as a contributor gene for obesity. A common G/A polymorphism in the UCP2 promoter region is associated with obesity and diabetes. As a cross-sectional study, 75 healthy 25-64 years volunteers were randomly selected from Tehran University of Medical Sciences population Lab. DNA was exracted from blood samples then polymorphism and A & G Allel frequencies were determined via PCR and RFLP. The correlation between genotype and such clinical and biochemical parameters as BMI, serum cholesterol and TG was investigated. Results were compared with other similar surveys. The frequencies of the UCP2 -866G/A genotypes in 75 Iranian normal population were AA: 7 (9.4%), GA: 41 (54.6%), and GG: 27 (36%). Significantly higher HDL cholesterol was detected in people with GG allele (P=0.02) as compared with GA and AA alleles. 866 UCP2 G/A genotype frequencies in our study were significantly different as compared with Japanese population but no with European studies that may emphasize on genetical similarity between Iranian and European Caucasians populations.

Obesity is an escalating public health problem. It is a major risk factor for atherosclerosis, hypertension, and type 2 diabetes. Since circulating levels of the adipocytokins are associated with obesity and dyslipidemia, we investigated the relationship of plasma adipocytokine concentrations with VLDL apolipoprotein B (apoB)-100 kinetics in men. Plasma adiponectin, leptin, resistin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) concentrations were measured using enzyme immunoassays and insulin resistance by homeostasis model assessment (HOMA) score in 41 men with BMI of 22–35 kg/m2. VLDL apoB kinetics were determined using an intravenous infusion of 1-[13C]leucine, gas chromatography–mass spectrometry, and compartmental modeling. Visceral and subcutaneous adipose tissue mass (ATM) were determined using magnetic resonance imaging, and total ATM was measured by bioelectrical impedance. In univariate regression, plasma adiponectin and leptin concentrations were inversely and directly associated, respectively, with plasma triglyceride and HOMA score. Conversely, adiponectin and leptin were directly and inversely correlated, respectively, with VLDL apoB catabolism and HDL cholesterol concentration (P < 0.05). Resistin, IL-6, and TNF-α were not significantly associated with any of these variables. In multivariate regression, adiponectin was the most significant predictor of VLDL apoB catabolism (P= 0.001) and, together with visceral ATM, was an independent predictor of plasma VLDL apoB concentration (P = 0.015); HOMA score was the most significant predictor of VLDL apoB hepatic secretion (P= 0.049). Leptin was not an independent predictor of VLDL apoB kinetics. Plasma VLDL apoB kinetics may be differentially controlled by adiponectin and insulin resistance, with adiponectin regulating catabolism and insulin resistance regulating hepatic secretion in men. But leptin, resistin, IL-6, and TNF-α do not have a significant effect in regulating apoB kinetics.

Although there is increasing evidences that vitamin D is related to the occurrence of diabetes mellitus, its relation to glucose metabolism in pregnancy is not well studied. This study investigated 25-hydroxyvitamin D deficiency status in GDM pregnant women. As a cross sectional study we recruited 741 pregnant women referred to five university educating hospital clinics. The universal screening was performed with a GCT-50g and those with plasma glucose level ≥130mg/dl, were diagnosed as GDM, if they had an impaired GTT-100g based on Carpenter and Coustan criteria. The levels of insulin was studied during OGTT-100g. Serum concentrations of 25-hydroxy vitamin D was measured too. Univeriate analysis revealed that 25 (OH) vit D concentrations were positively correlated with HOMA and ISOGTT index. Subjects with hypovitaminosis D (<12.5nmol/dl) had greater prevalence of GDM than others. The results reveal a positive association between 25(OH) vit D concentrations and insulin sensitivity. Vit D deficiency is more prevalent in patients with GDM than normal pregnant women, So vit D supplementation may control glucose levels and improves outcome of pregnancy.

Retinopathy is one of the microvascular complications of diabetes which is strongly related to the glycemic control and duration of the disease. According to results of other studies, the prevalence of retinopathy has been reported 5-30% in newly diagnosed patients whit type 2 diabetes (T2DM). The aim of this study was to determine the prevalence of idabeteic retinopathy among newly diagnosed T2DM patients in Isfahan, Iran. From july 2001 to March 2004, 710 newly diagnosed patients with T2DM were recruited in this study. Patients with duration of diabetes less than 1 year were considered as newly diagnosed ones. Along with physical examination and laboratory measurment for FBS, HbA1c, lipid profile, urea, Creatinin, and 24 houre urin examniation for albumin, retinoscopy was performed by an experienced ophttalmologist. In this study, 286 men and 424 women were investigated. The mean age of patients at presentation and the mean duration time of diabetes were 48.8 ±9.8 years (range 31-72years) and 8.6±5.4 months respectively. The prevalence of retinopathy was 9 % (9/8% in males and 8.5% in females). Logistic regression analysis revealed that BMI, diastolic blood pressure and 24 hour urine albumin, were independent risk factors for developing retinopathy. Nevertheless of relatively moderate prevalence of diabetic retinopathy in our study as compared with other studies, it is necessary to perform retinal examination in newly diagnosed T2DM patients in order to prevent the sight-threatening outcomes of diabetic retinopathy.

Medical-nutritional interventions, can reduce the risk of complicationsin T1DM. There has been some conflicting data on the issue of the association between diabetes knowledge and metabolic improvement of T1DM patients. Therefore the aim of this study was to evaluate the effect of nutrition education on biochemical changes, nutritional status, knowledge, attitude and practice of patients withT1DM in Aligoodarz. This study was a self – control quasi survey. Census sampling was used for subject selection. ِِData was collected by observation and interview techniques. Biochemical indices were measured on blood samples by standard methods and anthropometric measurements, diet survey and KAP study were carried out on 30 patients with T1DM by a nutritionist at the first and 3 months after training. All cases participated in educating programs for 12 hours. The results were analyzed by SPSS and Food processor softwares and results compared with paired t-test and McNemar test. P-values less than 0. 05 were considered as significant. 30 patients with 15 – 45 years old (Mean ± SD = 30. 8 ± 11. 3) participated in study all participants were educated. Mean duration of diabetes was 10. 9±6. 44 years. FBS, HbA1c, total cholesterol and LDL-C levels decreased significantly. After educating interventions also hypoglycemic attacks reduced. Macronutrients intake were in recommended ranges for diabetic patients. Simple carbohydrates and cholesterol intakes decreased and dietary Folate, Vit c and fiber increased. Calcium intake was less than RDA. Both knowledge and practice scores increased significantly (P<0. 001). Attitude was changed for some items significantly. Findings of this project emphasyzed on the importance of nutrition education to patients with T1DM. It may significantly changes biochemical indices, dietary fiber and simple carbohydrate and improves metabolic control in T1DM. And the patients KAP scores increased. Thus appropriate nutrition education as well as insulin therapy are the main factors in metabolic control of T1DM.

Women with polycystic overy syndrome (PCOS) are sussceptible for developing type 2 diabetes (T2DM) and cardiovascular diseases. In view increased prevalence of T2DM in patients with PCOS and priority of prescription agents capable to decrease insulin resistances for them, It is important to diagnose PCOS in T2DM patients. The aim of this study was to evaluate the prevalence of PCOS in T2DM women. Using ‘1990 National Institute of Child Health and Human Development Conference of PCOS’ criteria, 157 premenopausal women with T2DM were assigned into PCOS and non – PCOS groups after they were examined for the evidences of clinical PCOS. A questionnaire on reproductive history was completed and the waist circumference, weight, height and BP were measured for each participant. Biochemical tests were performed in both groups, but hormonal measurements were requested only for PCOS group. The prevalence of PCOS was high (about 8%) among subjects. Patients with PCOS had significantly lower age at the onset of diabetes, higher BMI and waist circumference. The differences in BP, serum TG, HDL, LDL, cholesterol and HbA1c were non – significant between 2 groups and insulin resistance is more. PCOS is prevalent in diabetic women and Insulin resistance is more likely in those with both PCOS and T2DM resistant than whom with diabetes alone. Emphasis on reducing insulin resistance may be of benefit to achieve a better diabetes control in these patients.

In many studies, Serum lipoprotein(a) [Lp(a)] levels considered as an independent risk factor for atherosclerosis. The aim of this study was to assess the association between Lp(a) and cervical carotid artery stenosis in one sample the Iranian population. As a cross sectional study, between June 2004 and January 2005, at Tehran Heart Center, 1189 candidates for any kind of open heart surgery, were recruited into this study. Carotid Dopplers ultrasonography was performed for all participants. Serum levels of Lp(a), total cholesterol, triglyceride and blood sugar and quantitative CRP were measured in fasting state and their correlations with carotid atherosclerosis were assessed. Among 1189 participants, 837 (70.5%) were male and 352 (29.4%) were female. Their mean age was 60±9.3 years (range between 35 to 88). There was not significant relation between Lp(a) serum levels and carotid artery stenosis (P=0.46). The relationship between Lp(a) levels and carotid artery stenosis in both ≤55 years and >55 years patients was not significant too (P=0.25). Also gender has no relationship in this regard (P=0.15). Significant relationship was found between Lp(a) level & hypoecho plaques (vulnerable lesions) (P=0.001). In our study, we found no significant correlation between serum Lp(a) and carotid stenosis. Lp(a) was found to have positive relationship with hypoecho plaques (vulnerable lesions) which predispose patients for CVA. Further investigations suggest for better evaluations.

Dyslipidemia accounts as a major risk factor for cardiovascular diseases. The aim of this survey was to determine the prevalence of dyslipidemia among relatives of patients with premature coronary artery disease (PCAD). As a cross-sectional study 232 first degree relatives of patients with PCAD were recruited. A questionnaire was filled out by all of the participants all of them undergone physical examination and blood sampling. Lipid profile was categorized according to the NCEP: ATPIII criteria. Total Cholesterol>200 in 29.7%, LDL>160 in 10.3%, HDL<40 in 12.9%, TG>200 in 32.8%, ApoB100>130 in 14.2%, Apo A1<90 in 1.7% and LP(a)>30 in 47% of participants were seen. Serum levels of TG were significantly higher in men than women levels of HDL and ApoA1 were lower in men than women. The Prevalence of dyslipidemia among relatives was 59.6%. In view of high prevalence of Dyslipidemia among relatives of PACD patients, active interventions in order to primary prevention of cardiovascular diseases via exact screening is recommended.