مجله دیابت و متابولیسم ایران
سال چهارم شماره 4 (پیاپی 10، تابستان 1384)

Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which T-cell mediated selective pancreatic β- cell destruction occurs. Half the risk of T1DM development is given by the HLA gene region while the remaining risk is assigned to non-HLA genes, probably those engaged in the formation of antigen interaction complex. The CD4 gene product, which is among the most prominent T-cell surface receptors with a key role in antigen processing, could be regarded as a strong candidate. We investigated the possible association of the CD4 gene polymorphism with T1DM using the candidate gene approach. The pyrimidine- rich pentanucleotide repeat polymorphism residing in the promoter region of the CD4 gene was studied. In the present study 92 Iranian T1DM patients and 108 healthy matched control individuals were screened by PCR technique. The analysis of our results shows the protective association of CD4*A3 (RR= 0.159, 95% CI: 0.036-0.707; Pc=0.025) and the susceptible role of CD4*A5 (RR= 7.379, 95% CI: 1.630-33.414; Pc=0.010) with T1DM. Our results suggest that the certain CD4 alleles are associated either negatively or positively with T1DM in the Iranian population.

Despite substantial progress in the clinical management of diabetes, diabetic nephropathy (DN) still occurs recurrently, implicating diabetes as the major underlying condition leading to the end stage renal disease. One of the main reasons is the influential role of genetic or inherited backgrounds of diabetics that are almost overlooked in daily practice. Owing to be orchestrated by the genetic makeup, cellular and molecular responses are different to similar metabolic disturbances. This in turn defines susceptibility/resistance state of the host to chronic diabetic complications, including DN. Separate analysis of every single gene that may be involved in genetics of a multi-factorial disease (such as DN) is the only available way to dissect the genetic basis of the disease and overcome its complexity. Among different genes accountable for DN, Transforming Growth Factor (TGF)-1 has an exceptional place. TGF-1 has profound impact on cell growth and proliferation, and in particular the regulation of extra cellular matrix deposition, branding it as a "pro-fibrotic" and "hypertrophic" mediator. By employing ARMS-PCR technique, the genetic susceptibility to DN was studied in 248 patients with T1DM (86 DN+, 162 DN−) and 113 healthy controls, all from British Caucasian origin. The analysis of two functional TGF-1 gene variations, which change codons 10 (+869*C/T) and 25 (+915*G/C) was carried out. There were some differences in alleles/genotypes distribution, but no significant association was apparent in patients as a whole or DN+/DN− subgroups and controls (P=NS). The negative result of this study may be false. As DN is a mortal disability, some fraction of risky genotypes associated with DN may previously be excluded by death. Such under-representation of the risky-genotypes (selective survivor effect) can be avoided by carrying out a prospective study. However, if the non-association result is true, it may question the functionality and reliability of the examined polymorphisms at least in the context of diabetes. Moreover, it does not underestimate the role of TGF-1 at the level of gene/protein themselves in development of DN.

Oxidized low-density lipoprotein (Ox-LDL), a key factor in the development of atherosclerosis, can cause endothelial dysfunction and augment lipid accumulation within the arterial wall. Increased oxidative stress in diabetes contributes to this process. Ox-LDL is a highly immunogenic molecule and it is not clear whether anti oxidized LDL antibodies (OLAB) are pathogenic or protective in atherosclerosis? The aim of this study was to evaluate Ox-LDL and its antibody in type 2 diabetes and healthy subjects. As a case-control study we evaluated 81 type 2 diabetic patients and 69 non-diabetic healthy persons aged 40 to 65 years. Controls were sex and BMI matched with diabetic patients. Patients with history of cigarette smoking, antioxidant or antihyperlipidemic drugs consumption, coronary heart disease, hypertension, and renal impairment were excluded. We measured serum level of Ox-LDL(two monoclonal antibody of Mercodia co.) and OLAB by ELISA. Lipid profile, serum electrolytes, and HbA1c (HPLC) were also determined. Ox-LDL and its antibody were compared between diabetic patients and controls and the correlation with lipid profile, HbA1c and BMI were assessed. Serum Ox-LDL concentration and Ox-LDL to LDL ratio were distinctively higher in controls (15.7+-6.9 vs. 11.8+-5.6, P < 0.005). Ox-LDL concentrations were correlated with LDL-C (rs=0.36, P<0.0005) and total cholesterol (rs=0.31, P<0.0005) in both groups but not with age and HbA1c. In diabetic patients, Ox-LDL and its antibody were positively correlated (rs=0.26, P<0.05). Obese diabetic patients (BMI > 30) had higher Ox-LDL concentrations in comparison with diabetic patients with BMI less than 30. In diabetic patients Ox-LDL level is lower than non-diabetics and is correlated with its antibodies. Based on previous findings, we suppose that the pattern of LDL oxidation enhances Ox-LDL recognition by macrophage via specific legends. This results in low serum Ox-LDL concentrations in diabetes.

Women with gestational diabetes mellitus (GDM) have a reported 3% to 65% risk of developing type 2 diabetes. This study aims to identify the factors in GDM patients which can predict the risk of postpartum impaired glucose tolerance (T2DM+IGT) and T2DM. A cohort study was conducted on 2416 pregnant women referred to five university 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. All pregnancies were followed 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. Such factors as FBS105 during pregnancy, insulin requirement during pregnancy and BMI≥27kg/m2 before pregnancy were more prevalent in postpartum diabetic patients as compared with normal controls, significantly. Multivariate analysis suggested that gestational requirement for insulin and BMI≥27kg/m2 were the best predictors for developing postpartum diabetes. Also history of abortion, gestational requirement for insulin and BMI≥27kg/m2 were the best predictors for postpartum IGT. Women with GDM have a substantially increased risk of developing postpartum IGT or diabetes. High glucose levels, insulin requirement during pregnancy, history of abortion and BMI≥27kg/m2 are the best predictors for postpartum diabetes and IGT.

Myocardial infarction is the most important cause of mortality all over the world. Complications may increase with some risk factors including stress hyperglycemia. The aim of this study was to evaluate the correlation and importance of hyperglycemia in acute intrahospital complications after AMI. Prevalence of stress hyperglycemia among 160 patients with acute myocardial infarction (Q wave MI) was determined. These patients were divided into normoglycemic and stress hyperglycemic groups. These were compared according to complications such as heart failure, cardiogenic shock and mortality. 61% were normoglycemic and 7.5% had stress hyperglycemia. 25% had history of diabetes and 4.4% were not aware of diabetes. Among 18 patients with stress hyperglycemia, 6 patient (50%) and among 101 normoglycemic patients 18 (17.8%) were affiliated with cardiac failure that the difference were significant (P=0.02 and χ 2= 6.25). There were no cases of cardiogenic shock in both groups. Three patients died during first hours of admission (2.97%). They hadnt have history of diabetes. We could not assign them to normoglycemic or stress hyperglycemic groups since blood sampling had not been done yet. Stress hyperglycemia can increase complications of AMI, significantly stress hyperglycemia caused increased incidence of heart failure in this study.

Foot complications are among the important problems of diabetic patients. Vascular and neurological involvements are two major causes for such complications. 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. 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. 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.

To evaluate the role of lipid markers including total cholesterol (TC), LDL-C and HDL-C vs. lipid indices (TC/HDL-C, LDL-C/HDL-C and non-HDL-C) as short term predictors of cardiovascular outcomes in adults over 30 years. As a nested case and control study, there were 207 CVD events among participants of Tehran Lipid and Glucose Study (TLGS) documented during 3 years of follow-up. Those cases that were free of CVD at baseline (132 subjects) were matched to 264 controls for age and sex. In all subjects, demographic and clinical data including blood pressure and anthropometric measurements as well as serum lipids, fasting and 2-hour glucose were available from the database of the TLGS. We estimated the relative risk (RR) for each lipid parameter in a multiple stepwise regression model after adjustment for family history of premature CHD, smoking, systolic and diastolic blood pressure, fasting and 2-hour plasma glucose and waist-to-hip ratio. The RRs associated with an increase of ≈1 SD of independent lipid predictors in the multivariate model were as follow: total cholesterol (RR=1.6 [1.2-2.0], SD= 1.3 mmol/L), LDL-C (RR=1.5 [1.1-2.0], SD= 1 mmol/L), non-HDL-C (RR=1.6 [1.2-2.1], SD= 1.2 mmol/L) and cholesterol/HDL-C (RR= 1.5 [1.1-2.0], SD= 1.8). The comparing of these four independent variables with ROC curve analysis showed that there was no significant difference in their predictive power for cardiovascular outcome. There was no association between HDL-C, triglyceride and LDL-C/HDL-C and CVD outcome in multivariate analysis. This study showed that TC, LDL-C, non-HDL-C and TC/HDL-C have similar predictive values for short term prediction of CVD outcome. It seems TC may be a reasonable choice for short term prediction of CVD outcome, because of lower cost.

Homocysteine is one of the novel cardiovascular risk factors. We know most of the cardiovascular and diabetes risk factors are accompanied. The aim of this study was to determine the role of homocysteine in diabetes. The study was performed in 25-64 year old individuals of the 17th district of Tehran according to WHO MONICA project. Homocysteine levels higher than 15 µmol/l was considered as abnormal. According to ADA 2004 criteria, fasting glucose levels of 100 to 125 mg/dl were considered as impaired glucose tolerance (IGT), while levels higher than 125 mg/dl included diabetes. Prevalence of hyperhomocysteinemia was 54.5% in the whole population. Prevalence of IGT and diabetes were 3.5% and 10.1%, respectively. There was no difference between prevalence of IGT and diabetes in both hyperhomocysteinemic and normal group (P= 0.365). The difference was also not significant in each genders, but mean glucose levels were significantly lower in people with hyperhomocysteinemia (P= 0.003). This study emphasizes that an inverse relation between glucose and homocysteine levels. Some studies indicate an opposite result and there is controversy on it. More researches may determine the exact role of homocysteine in diabetes.

Hyperhomocysteinemia may increase blood pressure by inducing endothelial cells dysfunction. The aim of this study was determining the relationship between plasma Homocysteine (Hcy) levels and blood pressure in new cases of type 2 diabetes mellitus. As a cross sectional study, 46 new cases of type 2 diabetes mellitus referred to Isfahan Endocrine and Metabolism Research Center were selected by convenient sampling. Basal characteristics of patients were recorded. Systolic and diastolic blood pressure was measured two times with 30 minutes interval on two consequent days. After ten hours of overnight fasting, blood samples were taken to measure fasting plasma glucose, HbA1c, triglyceride, Total cholesterol, HDL-C and creatinine. All data were expressed as mean (SD). Relationship between plasma Homocysteine levels and both systolic and diastolic blood pressure was assessed by Pearson's correlation coefficient. Patients were divided into three groups according to their plasma Homocysteine levels, (Hcy<10mol/L, 10Hcy<15 mol/L and Hcy15mol/L).. Then mean of systolic and diastolic blood pressure between groups were compared by one – way ANOVA and Tuckey-HSD tests. Mean (SD) of plasma Homocysteine levels was 12.2 (6.8) mol/L and of systolic and diastolic blood pressure was 128.8 (18.1) and 82.3(9) mm/Hg, respectively. There was a significant correlation between plasma Homocysteine levels, and both systolic (r=0.39, P<0.01) and diastolic (r=0.46, P<0.01) blood pressures. Mean (SD) of systolic and diastolic blood pressure in patients with plasma Homocysteine level of 15mol/L was 152.5 (17.7) and 91.8 (7.3) mm/Hg, respectively, so blood pressure in those group with hyperhomocysteinemia was higher than other two groups (P<0.001). There was no correlation between Homocysteine levels and FPG, HbA1c and lipid profile. There is a significant correlation between plasma Homocysteine levels and both systolic and diastolic blood pressure in newly diagnosed type 2 diabetics. Patients with hyperhomocyteinemia have higher blood pressure.

Pyomyositis is a pyogenic infection of the skeletal muscle characterized by muscle pain and swelling. The illness is more commonly seen in the tropics. The diagnosis of pyomyositis is difficult due to its vague clinical presentation and poor localizing signs. The differential diagnosis includes osteomyelitis, septic arthritis, muscle hematoma, muscle rupture and deep vein thrombosis. A delay in diagnosis may result in compartment syndrome, sepsis and death. Pyomyositis can be divided into three clinical stages: Stage 1 is characterized by crampy local muscle pain, swelling, low-grade fever and leukocytosis. The muscle may have a "woody" texture on palpation. Stage 2 is characterized by fever, muscle tenderness, and edema. Aspiration of the affected muscle typically yields pus. Stage 3 is characterized by bacteremia and a toxic appearance. Complications such as septic shock, endocarditis, pneumonia and some others may be present. Definite diagnosis should be made by aspiration or surgical drainage of the abscess. We report a 53 years old patient with diabetes who presented with a swelling and painful buttock and thigh, that was diagnosed with pyomyositis.