Association of polymorphism in both tryptophan 64 arginine of the beta 3-adrenergic receptor gene and TNF-alpha gene with features of the metabolic syndrome in Egyptians

Several candidate genes have been tested for their association with the metabolic syndrome. Among these genes, the Beta 3-Adrenergic receptor gene [ADRB3] and the TNF-alpha gene locus has been the object of many studies. Therefore the aim of this work was to investigate the possible association of the beta 3-Adrenergic Receptor Trp64Arg polymorphism and the -308G/A polymorphism in the promoter region of TNF-alpha, in a group of male Egyptians with features of the metabolic syndrome.30 male patients with features of metabolic syndrome [group I], fifteen age matched healthy males were included as controls [group II]. Patients and controls were subjected to full history taking, clinical examination stressing on blood pressure, waist circumference, and waist/ hip [W/H] ratio; laboratory investigations included lipid profile [TG, total cholesterol, HDL-C, LDL-C], FBS, fasting insulin and HOMA-IR index, and molecular detection of Trp64Arg variant of the beta 3- adrenergic receptor as well as the TNF alpha gene promoter polymoprhism using RFLP-PCR in blood. The studied clinical parameters, lipid profile, fasting blood sugar, fasting insulin and HOMA-IR index were significantly higher in group I than that observed in group II. There was no statistically significant difference between the beta 3- adrenergic receptor wild and mutant subjects among group I as regards the studied clinical parameters, lipid profile, fasting blood glucose, fasting serum insulin and HOMA-IR index. While subjects harboring the A allele of the TNF alpha gene promoter showed significant higher levels of fasting insulin [p=0.002] fasting blood glucose, [p=0.014] and HOMA index [p < 0.001] as well as a significant decrease in HDL cholesterol levels [p=0.041]. In contrast, no association was found with total cholesterol, LDL cholesterol, triglycerides levels between the different genotypes. The correlation between HOMA-IR index and other studied parameters was not statistically significant among group I. The beta-3-adrenergic receptor locus does not play an important role in the metabolic syndrome susceptibility or in the insulin resistance. While, the -308 G/A TNF-alpha gene variant might confer an increased risk for the development of insulin resistance

Levels of circulating soluble cell adhesion molecules in diabetics and in impaired glucose tolerance patients: correlation to stiffness index beta of the common carotid and femoral arteries

The current work was conducted to study the possible relationship between endothelial activation as assessed by the level of circulating soluble VCAM-1, ICAM-1, and E-selectin concentrations and atherosclerotic disease as assessed by the stiffness index 13 of the common carotid and femoral arteries in type 2 diabetic patients and patients with impaired glucose tolerance and the correlation of stiffness index beta of the common carotid artery and femoral artery with the degree of insulin resistance. Subjects and This study entailed 20 patients with type 2 diabetes meilitus, representing group I [GI], and 20 patients with impaired glucose tolerance, representing group II [GII] and 20 healthy subjects of matched age and sex as a control group, III [GIII]. All subjects were subjected to complete history taking and thorough clinical examination including body mass index [BMI]. Routine Laboratory investigations included oral glucose tolerance test [OGTT], glycosylated hemoglobin [HbA[1c]], serum uric acid, serum triglycerides, total serum cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], as well as liver and renal function tests were carried out by using standard commercial methods. The level of urinary microalbumin in GI, and insulin sensitivity assessment through OGTT, in all groups were carried out. Serum levels of the circulating adhesion molecules ICAM-1, VCAM-1 and E-selectin were measured in GI, II, and III by an enzyme-linked immunosorbent assay. All subjects were subjected also to radiological measurement of stiffness indexes beta of the common carotid and femoral arteries by high-resolution ultrasonography. sVCAM was found to be 681.2 +/- 81.8, 551.7 +/- 33.5, 453.4 +/- 28.4 ng/ml in GI, GII, and GIII, respectively. sICAM was found to be 339.4 +/- 18.8, 301 +/- 19.3, 197.8 +/- 9.2 ng/ml in GI, GII, and GIII, respectively. E-selectin was found to be 90.4 +/- 5.7, 69.8 +/- 6.8, 51.1 +/- 6.6 ng/ml in GI, GII, and GIII, respectively. Using LSD, sVCAM, sICAM, and E-selectin were found to be significantly increased in GI when compared to GII and GIII and to be significantly increased in GII when compared to Gill. Concerning stiffness index of carotid artery, it was found to be 28.7 +/- 8.3, 14.7 +/- 1.4, 12.1 +/- 1.6 in GI, GII, and GIII respectively. Using LSD, stiffness index of carotid artery was found to be significantly increased in GI when compared to GII and controls. With reference to stiffness index of femoral artery, it was found to be 30.3 +/- 7.1, 15.4 +/- 1.4, 12.7 +/- 2.4 in GI, GII, and GIII, respectively. Using LSD, stiffness index of the femoral artery, it was found to be significantly increased in GI when compared to GII and controls. It could be concluded that cAMs can be used as a marker of the stiffness index beta of both common carotid and femoral arteries due to the noted significant positive association. Stiffness index beta of both common carotid and femorai arteries are exacerbated in type 2 diabetic patients than in patients with impaired glucose tolerance and controls. The stiffness index beta of both common carotid and femorai arteries are associated with insulin resistance in type 2 diabetes meilitus. Further prospective studies should be carried to ascertain whether insulin resistance may induce the early changes of atherosclerosis in diabetes

Study of serum zinc, copper, magnesium, postassium and selenium in relation to serum Autoantibodies in siblings of type 1 diabetics

Aim: This work was intended to study the state of some elements namely zinc, copper, magnesium, potassium and selenium in sera of siblings of type 1 diabetic patients and its possible relation to some immunological markers. Subjects and The study included 208 subjects classified into 2 groups: group I included 108 siblings of type 1 diabetic patients and group II included 100 control subjects matched for age and sex. All subjects were subjected to the following: estimation of fasting and 2 hour postprandial plasma glucose and oral glucose tolerance test when needed. Determination of serum level of zinc, copper, magnesium, potassium and selenium was done using atomic absorption spectrophotometry. Measurement of serum insulin autoantibodies [IAA], antibodies to the protein tyrosine phosphatase-like proteins ICA512 [IA-2] and glutamic acid decarboxylase antibodies [GADA] was performed using radioimmunoassay [RIA] technique. The mean serum levels of zinc and copper were significantly higher [P = 0.000 for each], and the mean serum levels of selenium and potassium were significantly lower [P = 0.002 and 0.007, respectively] in type 1 diabetic siblings when compared with control subjects. Zinc and copper were significantly higher [P = 0.000 for each], and magnesium was significantly lower [P = 0.001] in the sera of siblings positive for IAA as compared to the seronegative cases. Selenium was found to be significantly lower in the sera of siblings positive for IAA, IA2 and GADA when compared to the seronegative cases [P = 0.000 for each]. Our results point to a disturbance in the serum levels of zinc, copper, selenium, potassium and magnesium. These nutritional elements may contribute as an environmental factor, that in conjunction with genetic factors, triggers the immunopathogenic sequence responsible, preceding and/or associated with beta cell damage in type 1 diabetes or its complications

Endothelial-dependent and independent vasodiatation; an index for endothelial dysfunction in women with previous gestational diabetes mellitus

Aim: This work was intended to assess whether healthy women with a history of gestational diabetes mellitus [GDM] may have abnormalities in endothelial function at a very early stage before glucose intolerance occurs. Subjects and the work included 45 subjects classified into 3 groups; I] included 15 obese women with previous GDM, II] included 15 nonobese women with previous GDM and III] included 15 nonobese healthy women as controls. All women were subjected to the following: thorough history taking, full clinical examination, laboratory investigations including serum uric acid, glycosylated haemoglobin, plasma endothelin-1 and complete lipid profile "total cholesterol, triglycerides, HDL-C and LDL-C". Oral glucose tolerance test [OGTT] was done using 75g glucose. Insulin sensitivity index and relative resistance for insulin were estimated during OGTT. The vasodilatory responses of the brachial artery during reactive hyperemia [endothelium-dependent Vasodilatation], and after nitroglycerine administration [endothelium-independent Vasodilatation] were measured using high-resolution echo-Doppler ultrasound 3-6 months after the last delivery. Flow mediated dilatation [FMD] was significantly and equally decreased in both groups of women with previous GDM, compared with control subjects [1.6 +/- 3.7% in the nonobese GDM group and 1.6 +/- 2.5% in the obese GDM group versus 10.3 +/- 4.4% in control subjects, P <0.05]. FMD correlated inversely and significantly with serum uric acid levels, BMI, serum total cholesterol, plasma endothelin-1 and relative resistance for insulin. Nitrate-induced dilatation [NID] was significantly decreased only in the obese GDM group compared with controls [21.4 +/- 5.1% versus 27.9 +/- 9.5%, P < 0.05]. OGTT was within normal range in all groups, although glucose concentrations at 30 and 60 min were significantly higher in both GDM groups, and glucose at fasting time, 90 and 120 min were significantly higher only in obese GDM women. Insulin levels at fasting, 30, 60, 90 and 120 min during the OGTT were significantly higher in obese GDM group. The relative resistance for insulin was significantly higher in the obese GDM group when compared with both the normal and nonobese GDM groups. Glycosylated haemoglobin levels were similar in all groups. Serum uric acid and plasma endothelin-1 were significantly higher in both obese and nonobese GDM women. Total cholesterol, triglycerides and LDL-cholesterol were significantly higher in obese GDM women. Conclusions: Our results suggest that endothelial dysfunction, which is considered as a very early index of atherogenesis, is already present in both obese and nonobese women with a history of GDM, even when they have normal glucose tolerance

Stiffness index beta of the common carotid and femoral arteries: relation to insulin resistance

This work was intended to study the association between arterial wall stiffness indexes beta of the common carotid and femoral arteries and insulin resistance in type 2 diabetic patients as well as patients with imparied glucose tolerance compared with age and sex matched control subjects. The study included 60 subjects classified into 3 groups; I] included 20 patients with type 2 diabetes, II] included 20 patients with IGT and III] included 20 matched controls. All patients and controls were subjected to the followings: complete history taking, thorough clinical examination, laboratory investigations including HBA1C, uric acid, complete lipid profile, microalbumin assay, renal and liver function tests. Measurement of insulin sensitivity by oral glucose tolerance test. Stiffness indexes beta of the common carotid and femoral arteries were measured by high resolution ultrasonography. The results of the present work can be summarized as follows: the stiffenss index beta [SI] of the common carotid and femoral arteries was significantly higher in diabetic group than those with IGT and controls [P< 0.001] for each], still those with IGT was insignificantly higher than controls [P < 0.05]. Also, stiffness index [SI] of the common carotid and femoral arteries was positively and significantly correlated with relative insulin resistance, total cholesterolm serum tryglycerides, LDL-C, uric acid, age and the duration of diabetes [P < 0.05]. Our results suggest that the stiffness indexes beta of the common carotid and femoral arteries were associated with insulin resistance in type 2 diabetic patients and such insulin resistance plays an important role in the pathogenesis of these sclerotic changes