مجله دیابت و متابولیسم ایران
سال ششم شماره 3 (پیاپی 20، بهار 1386)

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.

Single nucleotide polymorphisms of Adiponectin gene have been associated with BMI, insulin sensitivity and type 2 diabetes, reportedly. In present study we performed a genetic association study for Adiponectin gene at position +45*T/G in type 2 diabetes and normal subjects of Tehran population. Diabetic patients were selected from diabetes clinic and normal healthy control subjects aged between 25-64 years selected from zone 17 of Tehran. Adiponectin gene polymorphism was analyzed using PCR-RFLP method in normal healthy controls (N=70), obese diabetic patients (N=80) and non-obese diabetic patients (N=72). Frequency of TT genotype was 62.5% in non-obese diabetic patients and 78% in control group, that was statistically significant (TT vs TG+GG: P=0.02, OR=2.2, CI:0.98-5.00). There was also a significant difference for allele T and G frequencies when we compared between non-obese diabetic patients and controls group. The frequency of allele G was increased in non-obese diabetic (20.1%) patients compared to controls (12%) (P: 0.04 OR: 1.8 CI: 0.9-3.7). This study showed TG and GG alleles of Adiponectin gene polymorphism at position +45*T/G are risk factors for development of diabetes mellitus while this effect is independent from BMI and obesity.

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). 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. 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. 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.

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. 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. 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. 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.

Atherosclerosis is the leading cause of death necessitates more research to find better solutions to this general concern. Due to the side effects of chemical compounds, more attention has been paid to herbal remedies. This study was designed to investigate the effects of Nigella sativa, on atherosclerosis and its risk factors in hypercholesterolemic rabbits. Fifteen rabbits were randomly distributed into three groups of five each.(Normal diet group, hypercholesterolemic diet group (1% cholesterol) and group that received hypercholesterolemic diet supplemented with 5% nigella sativa). Animal groups received their own diets and water for a period of 8 weeks. At the beginning of the treatment period, blood samples were taken from all animals to measure biochemical factors. Same procedure was performed at the end of the period then the left and right coronary arteries and the aorta of each animal were dissected to study fatty streak formation (FSF). Dietary use of Nigella sativa significantly decreased cardiovascular FSF as well as blood cholesterol and LDL in hypercholesterolemic animals. Though not significant but blood HDL was increased and reduction in C-reactive protein (CRP), triglyceride (TG) and oxidized LDL was observed in the same animals. The results indicate that Nigella sativa inhibits the development of atherosclerosis. This may be related to the effect of Nigella sativa on plasma lipoproteins in addition to its antioxidant and anti-inflammatory properties.

To determine the prevalence and characteristics of subjects with isolated post challenge hyperglycemia (IPH) defined as fasting plasma glucose (FPG) <126 mg/dl and 2-hour plasma glucose (2h-PG) ≥200 mg/dl. We evaluated data and results of Oral Glucose Tolerance Test (OGTT) from 9745 participants in Tehran Lipid and Glucose Study (5589 women and 4156 men) aged>20years, without previously diagnosed diabetes mellitus (DM). A logistic regression model for having IPH was developed among subjects with FPG<126mg/dl to predict. The prevalence of IPH was 3.1% (n=302). 26.5% (n=80) of subjects with IPH had FPG<100mg/dl. The odds ratios for IPH were statistically significant for FPG≥100mg/dl (OR=9.5; 95% CI: 7.1-12.5), age≥40 years (OR=2.6; 95% CI: 1.8 - 3.7), triglycerides≥200 mg/dl (OR=2.1; 95% CI: 1.6-2.7), hypertension (OR=2.0, 95% CI: 1.5-2.6) and abnormal waist circumference (females≥80, males≥90cm) (OR=1.9, 95%CI: 1.3-2.8). This analysis showed that in Tehran urban subjects with FPG<126 mg/dl, variables such as FPG≥100 mg/dl, older age, hypertriglyceridemia, hypertension and abnormal waist circumference were significantly associated with higher likelihood of IPH; OGTT would hence be recommended in subjects with above mentioned characteristics.

The aim of this study was to determine the prevalence of cardiovascular disease (CVD) risk factors among type 1 diabetic patients referring to Isfahan Endocrine & Metabolism Research Center. In this cross-sectional study, the prevalence of CVD risk factors including dyslipidemia, smoking and hypertension was determined in type 1 diabetic patients aged 15-30 years. Serum cholesterol <170 mg/dl, LDL<100 mg/dl, HDL>35 mg/dl, TG<150 mg/dl, systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg were considered as optimal control levels. Among 219 studied diabetic patients (mean age=22.5±10.3, female/male=120/99), the mean cholesterol and HDL-C level was higher in women (176±34.9, 46.4±34.1) than men (162.9±32.4 vs. 41.5±10.1) (P<0.05). The prevalence of smoking, hypercholesterolemia, LDL>100 mg/dl, HDL<35 mg/dl, hypertriglyceridemia and hypertension was 6.9% (n=15), 47.4% (n=104), 53.5% (n=117), 22.8% (n=50), 18.3% (n=40) and 7.7% (n=17), respectively. HDL<35 mg/dl was more prevalent among men as compared with women but cholesterol> 170 was more frequently detected in women (P<0.05). Considering the rather high prevalence of CVD risk factors in type 1 diabetic patients in Isfahan, and in view of modifiability of these risk factors, educating patients on appropriate glycemic control and increasing physical activity is necessary as well as close monitoring of these risk factors.

Type 2 diabetes mellitus is a common metabolic disorder witht increasing prevalence is increasing worldwide. C-Reactive Protein (CRP) is a marker of systemic inflammation and an independent risk factor for cardiovascular disease (CVD). The aim of this study was to elucidate the correlation between glycemic control and systemic inflammation by measuring serum CRP levels. In this cross sectional study 136 patients with type 2 diabetes mellitus (69 females, 67 males) were recruited. In addition to measurement of CRP levels by highly sensitive methods and measurement of hemoglobin A1C effects of influencing factors on the CRP level was considered. Fasting plasma glucose was determined via the glucose oxidase method, HbA1C via HPLC, serum lipid profile enzymatically and hs-CRP with sandwich immunoassay method. The mean concentrations of CRP levels in these patients (5.2 ± 4.8 mg/L) were higher than normal range and in women greater than men (6.4 ± 5.5 vs. 3.9 ± 3.6 mg/L). Before adjusting for influencing factors the association between hs-CRP levels and hemoglobin A1C was negative but not statistically significant (r= -0.15, P=0.07). After adjusting, the association was negative and significant. (r= -0.22, P= 0.02). In this study the relation between hs-CRP and lipid profile was also determined. There was no significant relationship between the levels of hs-CRP and total cholesterol, LDL-C and HDL-C. A positive correlation between hs-CRP with serum triglyceride and triglyceride / HDL ratio was observed. However, the correlation was not significant. These results demonstrate that hs-CRP levels is influenced with multiple factors, and increased hs-CRP levels in patients with type 2 diabetes mellitus can not be explained with hyperglycemia alone.

Limited data are available relating intake of fruits and vegetables to inflammatory markers and risk of metabolic syndrome. The aim of this study was to evaluate the relationship between fruits and vegetables intake and C-reactive protein (CRP) and the prevalence of the metabolic syndrome. Fruits and vegetables intake were assessed using a validated semi-quantitative food frequency questionnaire in a cross-sectional study of 486 Tehranian female teachers aged 40-60 y. Anthropometric measurements were done and blood pressure was assessed according to standard methods. Fasting blood samples were taken for biochemical measurements. The metabolic syndrome was defined according to Adult Treatment Panel III guidelines. The reported mean daily intake of fruits and vegetables were 228±79 and 186±88 g/d respectively. Both fruits and vegetables intake were inversely associated with plasma CRP concentrations. After statistically controlling for age, BMI and waist circumference, mean plasma concentrations of CRP across increasing quintile categories of fruits were 1.94, 1.79, 1.65, 1.61 and 1.56 mg/L respectively (P for trend <0.01) and of vegetables were 2.03, 1.82, 1.58, 1.52 and 1.47 mg/L respectively (P for trend<0.01). These inverse associations remained significant after additional control for other potential confounding variables and dietary factors. After controlling for potential confounders individuals in the highest quintile of fruits intake had 34% (95% CI: 20%-46%) lower and those in the highest quintile of vegetables intake had 30% (95% CI: 16%-39%) lower chance of having the metabolic syndrome compared to those in the lowest quintiles. In this study higher intake of fruits and vegetables were associated with lower risk of metabolic syndrome; part of this association may be mediated through CRP. These findings support current dietary recommendations to increase the intake of fruits and vegetables as a primary preventive measure against cardiovascular disease.

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. 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. 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. 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.

Type 2 diabetic patients have higher risk for death from coronary heart diseases than non-diabetic patients. Studies have revealed showed intensive treatment of hyperglycemia only have a small effect on CVD risk. Other risk factors such as Lipid abnormality play a leading role in the increased CVD risk associated with diabetes. The aim of this study was to assess the quality of lipid control and treatment in type 2 diabetic patient with dyslipidemia. We studied Data from 602 type 2 diabetic patients who had at least four regular clinic visits every year for medical care in outpatient clinics of Isfahan Endocrinology and Metabolism Research Center, 1999-2003. Patients for Classified in three groups according to lipid levels as low, moderate and high risk. ADA)American Diabetes Association) standard criteria were used for appropriate lipid control. The mean age, duration of diabetes, HbA1c and BMI were 52.2±9.5 years, 6.8±4.6 years, 9.2±1.7% and 29.4±4.2 Kg/m2 respectively at initial registration. Eighty four percent of patient had LDL cholesterol above 100 mg/dl and 71% had triglyceride level >150 mg/dl, of these patients 47.8% and 41.6% had high risk levels and only 12.4% taking statins and 21.5% taking fibrate for treatment at end of study. Among hyperlipidemic patients levels of LDL-C decreased from 170.8±35.6 mg/dl to119±30.20 (p <. 001), triglyceride decreased from 273.8±126 to225.2±97 mg/dl (P<0.004) and HDL-C increased from 43.3±10.6 to 48.4±14.1mg/dl ((P<0.6). Percentage change of lipid level was -35.8%, -17.7% and +7.3% respectively. At the end of fallow-up 50.4% of patients treated with statins and 14.7% with fibrate. Finally, overall control of cholesterol and triglyceride in patients with dyslipidemia was 30% and 37% respectively. Our findings showed that many of type 2 diabetic patients with dyslipidemia have inadequate control of lipid and lipoprotein. The prevalence of cardiovascular events due to hyperlipidemia in type 2 diabetic patients is high. This fact demonstrates the importance of early interventions for control and treatment these risk factors for prevention of cardiovascular complication in this patients.

Pemphigus vulgaris is the most common autoimmune blistering disease. Corticosteroid is treatment of choice for it. Medication can affect many organs and causes metabolic difficulties which steroid- induced diabetes (SID) is one of the most important side effects. Determining risk factors not only help identify diabetes in early stages but also let continuing treatment of underlying disease. Sixty eight patients with recently diagnosed pemphigus vulgaris were recruited. After admitting in hospital they were evaluated for positive family history of diabetes, blood pressure, body mass index (BMI), FBS, HbA1c, TG and HDL. Then they followed with FBS twice per week for 8 weeks. Ninety patients (27.9%) developed diabetes. In comparison with non-diabetic group, diabetic group had a significantly higher HbA1c>6% (NL: 4.5-6.8) or: 8.39 (CI: 1.46- 48.05), TG > = 200 or: 6.56 (CI: 1.64-28.18) and IFG or: 3.11 (CI: 1.04-9.31). There were no differences between the groups in respect of age, positive family history, blood pressure, BMI, HDL. These findings suggest that HbA1c,TG and IFG are independent risk factors; so patients with pemphigus vulgris who are candidates for steroid treatment should be evaluated for HbA1c, TG and IFG before treatment.