role of proinsulin in gestational diabetes mellitus

To look for any increase in proinsulin or proinsulin/insulin ratio in women suffering GDM as an additional factor to their insulin resistance state during pregnancy; and to test for its reversibility in the post partum period. The study was conducted on 30 pregnant age matched women in their second or third trimester and 10 age matched non pregnant normoglycemic women as a reference group. The pregnant women were divided into 3 groups each of ten as follow: normoglycemic women with normal OGTT as a control group, obese women with GDM and lean women with GDM. All women were subjected to full history taking and complete clinical examination. The following parameters were measured: diagnostic OGTT using 100 gm glucose, fasting serum proinsulin, fasting serum insulin, serum C-peptide, proinsulin/insulin ratio and insulin sensitivity. All these tests were repeated 4-8 weeks postpartum. The results of the study revealed that the serum levels of proinsulin and the proinsulin/insulin ratio were significantly higher in obese and lean women with GDM than the control and reference groups during pregnancy and also after delivery. The insulin sensitivity index was significantly lower and the relative resistance for insulin was significantly higher in GDM women compared with normal glucose tolerant pregnant women during pregnancy, while after delivery the sensitivity index was significantly higher than during pregnancy in GDM women as well as pregnant women with normal OGTT. The mean values of C-peptide were significantly higher in GDM patients versus control and reference groups during pregnancy. After delivery these mean values of C-peptide were significantly lower than during pregnancy in the three pregnant studied groups. Women with GOM are characterized by elevated serum proinsulin concentrations and increased proinsulin/insulin ratio which reflect beta-cell decompensation. These precursors molecules might thus serve as a marker for the disease and potentially even identify the subjects of high risk for development of type 2 diabetes. Also, it may be possible to detect such beta-cell stress earlier in pregnancy and to use this phenomena in the assistance of better prediction of GDM

Eotaxin and other immunological markers, metabolic and anthropometric factors in relation to circulating adiponectin level in type 2 diabetic patients and individuals with impaired glucose metabolism

Hypoadiponectinemia is associated with insulin resistance and predicts the incidence of type 2 diabetes and coronary artery disease. Chronic subclinical inflammation and activation of innate immunity are involved in the pathogenesis of type 2 diabetes. Since obesity is associated with hypoadiponectinemia and with increased circulating levels of various immunological markers, which are both major risk factors for the development of type 2 diabetes, so the aim of this study was to investigate the association of hypoadiponectinemia and low grade systemic inflammation in type 2 diabetic patients as well as subjects with impaired glucose tolerance. Sixty male age matched subjects were included in the study. They were divided into 3 groups each of twenty as follows: newly diagnosed patients with type 2 diabetes mellitus [group I], patients with impaired glucose tolerance [group II] and healthy subjects with normal glucose tolerance [group Ill] as a control group. Patients and controls were subjected to full history taking, clinical examination stressing on blood pressure, BMI and WHR; laboratory investigations including FPG, PPG, HbA1C, fasting insulin and HOMA-IR index, lipid profile [TG, total cholesterol, HDL-C, LDL-C], serum uric acid, serum adiponectin and some immunological markers including WBC, acute phase reactants [CRP], TN F-alpha and eotaxin. In type 2 diabetic patients, plasma adiponectin levels were strongly negatively correlated with CRP, fasting TG, fasting insulin, HOMA-IR and fasting glucose [P < 0.001] and strongly positively correlated with HDL-cholesterol [P < 0.001]. Inverse correlations were found between adiponectin levels and WHR, postprandial glucose, and TNF-alpha [P < 0.05]. No significant correlation was found between adiponectin level and eotaxin [P > 0.05]. In subjects with IGT, an inverse relation was found between adiponectin and fasting glucose [P < 0.05]. The mean values of immunological markers [eotaxin, TNF-alpha, CRP and WBC] were significantly higher in type 2 diabetics versus control group. Subjects with IGT showed significant lower levels of eotaxin and TNF-alpha than diabetic patients, while they showed significant higher levels of eotaxin, TN F-alpha and CRP than controls [P < 0.05]. The mean value of adiponectin was significantly lower in type 2 diabetic patients than in subjects with IGT and the control group [P < 0.05]. The studied clinical and anthropometric parameters, lipid profile, parameters of glycemic control, fasting insulin and HOMA-IR were significantly higher in group I versus group II and the control group [P < 0.05]. Our results support the hypothesis that hypoadiponectinemia may be associated with low grade inflammation, metabolic abnormalities and dyslipidemia. Therefore, adiponectin may be an important link between inflammation and type 2 diabetes as it was negatively correlated with markers of inflammation in such patients

Human resistin gene polymorphism: association with serum resistin level and insulin resistance in type 2 diabetes mellitus

Resistin is an adipocyte - secreted cytokine associated with insulin resistance in rodents. In humans, it remains controversial whether circulating resistin levels are associated with insulin resistance, type 2 diabetes, or obesity. The role of resistin gene, referred to RETN, in human type 2 diabetes or obesity is largely unclear in studies of its association with SNPs or serum resistin. Major genetic factors of type 2 diabetes, a probable polygenic disease, remain to be identified. Therefore the aim of our work was to study circulating level of resistin and to correlate this level with resistin gene 3'UTR+62G-A polymorphism and factors related to insulin resistance in type 2 diabetic patients. 40 male patients with type 2 diabetes [group I] and 10 age-matched healthy controls [group II] were included. All patients and controls were subjected to full history taking, clinical examination stressing on waist circumference, BMI and blood pressure. Laboratory investigations included lipid panel [TG, total cholesterol, HDL-C and LDL-C], glycemic parameters [FBS, Hb A1c, fasting insulin, HOMA, IR], serum uric acid, highly sensitive CRP, serum resistin and molecular detection of resistin gene 3'UTR+62G-A polymorphism using PCR-RFLP. Serum resistin levels, highly sensitive CRP, anthropometric measures and metabolic parameters were significantly higher in type 2 diabetic patients [group I] than in healthy controls [group II] [P<0.05]. In type 2 diabetic patients the serum resistin was negatively correlated with HDL-C and positively correlated with BMI, HOMA-IR and highly sensitive CRP [P < 0.05]. In diabetic subjects the genotype distributions of resistin gene 3'UTR polymorphism were as follows: 3 [7.5%] subjects were heterozygous [GA], 1 [2.5%] was homozygous [AA] for the mutant allele and 36 [90%] were homozygous [GG] for the wild allele. Type 2 diabetic subjects had a significantly lower frequency of resistin gene 3'UTR + 62A variant [GG: GA/AA, 90%:10%] than control subjects [GG: GA/AA, 60%:40%; odds ratio, 6.0; 95% confidence interval, 1.17 to 30.7; P = 0.041]. G allele was linked to greater insulin resistance as indicated by higher HOMA-IR index [P = 0.004]. Also diabetic subjects harboring the G allele showed significant higher levels of serum resistin, BMI, highly sensitive CRP as well as a significant decrease in HDL-cholesterol [P = 0.042, 0.007, 0.008, 0.003 respectively]. These findings suggest that resistin gene 3'UTR + 62G-A is associated with serum resistin level and may play a role in the pathogenesis of type 2 diabetes and insulin resistance. The strong correlation of resistin with highly sensitive CRP suggests that resistin may be considered as inflammatory marker associated with type 2 diabetes

Study of plasma visfatin level in women with gestational diabetes mellitus during and after pregnancy and its relation to insulin sensitivity

The insulin-mimetic adipocytokine visfatin is highly expressed in visceral fat and whose blood levels correlate with obesity. It lowers blood glucose, improves insulin sensitivity, and recently found to act as an insulin analogue on the insulin receptors. It has been associated with insulin resistance in some studies and regulated by glucose. To evaluate the role of visfatin in GDM, typically associated with increased insulin resistance, we determined visfatin levels in women with GDM and in healthy pregnant controls. Furthermore, visfatin concentrations were investigated after delivery in a subgroup of women with GDM. 30 women with GDM [group I] and 15 age-matched healthy pregnant controls [group II] at 24-28 weeks of gestation were included in the study. All women were subjected to full history taking, complete physical examination and anthropometric measures including BMI and WHR. Venous blood samples for lipid profile, glucose, insulin and visfatin concentrations were taken 1 hour before a standard 75g OGTT and was carried out after overnight fast. Venous blood samples were repeated for glucose, insulin and visfatin 30, 60, 120 minutes after an oral glucose load. Insulin sensitivity was estimated using ISI derived from OGTT. A subgroup of 15 women with GDM [group III] was investigated for all these parameters 2 weeks after delivery. Fasting plasma visfatin concentrations were significantly higher in the gestational diabetes mellitus group during the course of pregnancy [69.04 +/- 18.41 ng/ml] than in healthy pregnant control group [31.22 +/- 24.74 ng/ml] [P<0.05]. The fasting plasma levels of visfatin showed significant drop in GDM women 2 weeks after labour [45.86 +/- 6.89 ng/ml] than during the course of pregnancy [69.04 +/- 18.41 ng/dl] [P<0.05]. The glucose-induced changes in visfatin and insulin calculated by AUC were significantly higher in GDM group during pregnancy than in healthy normal controls. The mean values of the area under the curve for glucose, insulin and visfatin curves showed significant reduction in GDM women 2 weeks after labour [P<0.05]. Significant positive correlations were detected between fasting visfatin and WHR, fasting glucose, as well as fasting insulin in GOM women during pregnancy and 2 weeks after labour. Fasting visfatin levels were negatively and significantly correlated with peripheral insulin sensitivity index in the three studied groups [P<0.05]. The precise significance of our findings indicates that adipocytokine visfatin may play a role in the pathogenesis of gestational diabetes mellitus. However, the study of the regulation of visfatin in GDM merits further considerations and further experiments are needed to clarify its role in such disease