ACTA ENDOCRINOLOGICA (BUC)

Abstract. Preeclampsia is a widespread vasospasm and vascular endothelial dysfunction that usually occurs after 20 weeks gestation. Uterine artery Doppler is a good sensitive predictor. PP13 (as a chemical predictor) was claimed to provide similar results. Objective. To evaluate whether first trimester maternal serum placenta protein 13 (PP13) and the second trimester uterine artery Doppler pulsatility index can predict pre-eclampsia among high risk Egyptian pregnant females. Design. The study took place in obstetric clinic of Kasr Elaini Hospital (Faculty of Medicine - Cairo University) in the period October 2011 - August 2012. Subjects and Methods. The study included 59 pregnant women (11- 13 weeks), 34 normal controls and 25 women at increased risk of developing pre-eclampsia. PP13 was assayed using enzyme-linked immunosorbent assay. Uterine artery Doppler flow velocimetry was done at 22–24 weeks to measure the mean pulsatility index (PI). PP13 multiples of median (MoM) were calculated.PP13 and Uterine artery Doppler PI were compared between women who developed pre-eclampsia and controls. Results. Levels of PP13 were not found to differ between control and affected pregnancies. PP13 MoMs for controls and pre-eclampsia cases were 1.000 (0.516) and 1.7200 (0.851), respectively (P=0.4). PI was significantly higher in affected cases 1.62(0.2) compared to controls 1.24(0.2) (P <0.001). Conclusion. Screening test based only on maternal history or PP13 testing is inefficient in predicting preeclampsia in high risk females. Abnormal uterine artery Doppler velocimetry between 22 and 24 weeks of gestation is still the best test for identification of patients destined to develop preeclampsia.

Objective. To investigate the impact of body weight on the subclinical hypothyroidism observed in patients with PCOS. Methods. The study included 95 normal weight (Group-1) and 122 overweight or obese women (Group-2) with PCOS. The control group consisted of age and BMI matched healthy individuals and grouped as normal weight (n: 66, Group-3) and overweight or obese (n: 65, Group-4. Women with chronic disease such as overt thyroid dysfunction, late-onset adrenal hyperplasia, and diabetes were excluded from the study. Plasma glucose and lipid profile, thyroid hormones, insulin, FSH, LH, total testosterone, estradiol, progesterone and DHEA-S were measured. Results. While fasting glucose was similar, insulin and HOMA-IR were higher in Group-2 and Group-4 (p: 0.001). The groups were similar with respect to FSH, Estradiol, prolactine, DHEAS. While total testosterone and LH levels were higher (ptestosterone: 0,009), progesterone was lower in both PCOS groups (pprogesterone: 0.041). Free T3, free T4, thyroid antibodies were similar between the groups, but the prevalence of subclinical hypothyroidism was greater in Group-2 and -4 than in Group-1 and -3 (p: 0.044). TSH was only correlated with BMI (r: 0.122, p: 0.02). Conclusion. The increased prevalence of subclinical hypothyroidism in women with PCOS might be the result of increased BMI.

Background. We aimed to evaluate whether a high carbohydrate or a high fat diet differs in alteration of the inflammatory and metabolic risk factors in cardio-renal metabolic syndrome in rats. Methods. Twelve male Wister rats were randomly divided into two groups: one received diet 1 standard pellet rat diet (D1) containing 10% fat, 50% carbohydrate, 25% protein and another group received diet 2 (D2) containing 59% fat, 30% carbohydrate and 11% protein for 16 weeks. Weight was recorded weekly. FSG and insulin levels were measured using an enzymatic spectrophotometric and a standard ELISA kit respectively. Inflammatory parameters including TGF-β, MCP-1, TNF-α, IL-1β, IL-6 in the renal and cardiac tissues of rats were evaluated by ELISA technique. Result. Food intake in D1 and D2 groups increased in the study period, however food intake in D2 group was significantly higher compared with D1 group. FSG, HOMA and TG concentrations in D2 group were significantly higher compared to D1 group. Moreover, TGF-β and MCP- 1 concentrations in the renal tissues of D2 group and TNF-α in the cardiac tissues of D1 group were significantly higher compared with D1 group (P<0.05). Positive associations between IL-1β and TG and between HOMA, FSG with TGF-β and MCP-1 in the renal tissue of animals were also identified.

Background. To investigate the association between inflammatory factors, such as complete blood count (CBC) components, neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and gestational diabetes mellitus (GDM). Methods. A total of 635 pregnant women with GDM and 296 with normal pregnancies at 7–13 weeks of gestation who underwent prenatal examinations in the obstetrics department were enrolled (June 2020–December 2020). CBC parameters, including WBC, neutrophil, lymphocyte (LYM), monocyte (MON), red blood cell (RBC), hemoglobin (HGB), mean corpuscular volume (MCV), platelet (PLT), platelet accumulation (PCT), mean platelet volume (MPV), NLR, MLR, PLR, alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), and other parameters were assessed. The receiver operating characteristic (ROC) curve was used to analyze the screening effects of the variables on the development of GDM. Results. There were significant differences in the blood levels of WBC, NEU, LYM, MON, RBC, HGB, PCT, ALT, AST, GGT, NLR, and MLR between the GDM and control groups (P<0.05). The diagnostic level of MON was the highest among all factors. Conclusion. Inflammatory factors (WBC, NEU, LYM, MON, NLR, and MLR counts) were correlated with GDM.

Context. Changes in the secretion of signaling molecules that originates from adipose tissue and inflammation draw attention in the pathogenesis of type 2 DM. Chemerin, one of the signaling molecules of adipose origin, and irisin, defined as the Renaissance of the metabolism, are among these molecules. Objectives. This cross-sectional study was planned in order to compare the values of serum irisin and chemerin levels in patients newly diagnosed with T2DM and in healthy subjects. Subjects and Methods. The study included 41 patients newly diagnosed with T2DM and 49 healthy individuals. The chemistry parameters were analyzed with a biochemistry autoanalyzer, and hormonal parameters were analyzed with an immunoassay analyzer. Plasma irisin and chemerin levels were measured using the enzyme-linked immunosorbent assay method. Results. There was a significant difference between the groups in terms of glucose, HbA1C, Insulin, HOMA-IR and lipid panel results. Irisin levels in the group of patients newly diagnosed with T2DM were lower than in the control group. Chemerin levels in the group of patients newly diagnosed with T2DM were higher than in the control group. Conclusion. Consequently, diabetes-dependent changes in chemerin and irisin concentrations suggest that these two hormones have a role in the pathophysiology of DM. Further studies are required to understand the complex structure of the signaling pathways of chemerin and irisin molecules as well as the physiological importance of these molecules as metabolism regulators especially in humans.

Context. Data are conflicting concerning risk for Alzheimer’s disease (AD) and 5,10-methylenetetrahydrofolate reductase genetic variant (MTHFR C677T). Objective. The aim of the study was to investigate the associations of MTHFR C677T and risk of developing AD. Design and Methods. We searched the relevant articles by using Medline, web of science, and abstracts of conference proceedings. The meta-analysis and statistical analyses were performed using Stata. Results. In 33 included studies which provided 4518 cases and 5476 controls, the analysis for investigating the association between C677T allele T and the risk of developing AD relative to the allele C revealed no heterogeneity (p=0.088, I2=26.1%) between the 33 studies; the random effects (RE) pooled OR was significant: [RE OR=1.13(1.05-1.22)]. In subgroup analysis, we only observed the significant results in Asian populations. The pooled analysis for MTHFR 677 CT+TT vs. 677CC revealed a significant result [fixed effect (FE) OR=1.22(1.10-1.34)]. However, we did not observe significant associations in Europeans when comparing MTHFR 677 CT+TT with 677CC in subgroup analysis. The pooled analysis for MTHFR 677 TT vs. 677CC+CT did not reveal significant results: [FE OR=1.08(0.95-1.22)]. Conclusion. The risk allele T of MTHFR C677T is associated with high risk of AD in Asian populations, but not in Europeans.

Context. Results concerning the relationship between the risk of developing diabetic retinopathy (DR) and methylenetetrahydrofolate reductase genetic variant (MTHFR C677T) are inconclusive. Objective. The aim of the present analysis was to investigate the associations of DR with MTHFR C677T. Design and Methods. We searched the relevant articles by using Medline, web of science, and abstracts of conference proceedings. The meta-analysis was performed using Stata. Results. The included 7 studies provided 535 cases of DR and 759 controls. The main analysis for investigating the association between MTHFR 677 TT and the risk of developing DR relative to the 677 CC did not reveal significant heterogeneity (p=0.227, I2=27.6%) between the studies; the fixed effects (FE) pooled OR was significant: FE OR=1.84(1.30-2.61). The analysis for the association between MTHFR 677 TT and the risk of developing DR relative to the 677 CC+CT revealed heterogeneity (p=0.082, I2=48.9%) between the studies; the random effects (RE) pooled OR was significant: RE OR=1.72(1.07-2.76). In addition, T carriers have 31% higher risk of developing DR compared with homozygotes for C [OR=1.31(1.03-1.66)]. Conclusions. The present metaanalysis suggested an association between MTHFR C677T and DR and provided evidence that the TT genotype of the MTHFR C677T contributes to susceptibility to DR.

Objective. To evaluate the effect of multiple daily injection (MDI) treatment replaced by Exenatide BID as compared with continuation of MDI. Patients and Methods. A total of 140 patients with type 2 diabetes, taking metformin and multiple daily insulin injections, were randomized to exenatide or insulin group that continued their insulin treatment. Patients were followed-up for 16 weeks. Blood glucose profiles, BMI, waist circumference, HbA1C, serum lipids and side effects were assesssed at weeks 0,12 and 16. Results. There were no significant differences between the two groups with respect to baseline parameters. Glycemic control was similar between the two groups. The mean changes in HbA1C in exenatide group were -0.66±0.63% and in insulin group -0.74±0.92 % (p=0.594). In exenatide group, 59.6 % of patients and in insulin group 85.71 % of patients had maintained or improved glycemic control at the end of the study. In insulin group, insulin requirement increased 5.86 ± 4.46 units/day. Body weight and waist circumference decreased significantly in exenatide treatment group with respect to insulin group (p<0.001). Conclusions. Substituting exenatide for insulin might be an option in insulin-treated, type 2 diabetic patients having obesity, and poor glycemic control. However, patients with longer duration of diabetes and insulin treatment and with lower C-peptide levels might not benefit from exenatide therapy.

Objective. The aim of this study was to evaluate the possible protective effects of MT against gastric oxidative stress and dyslipidemia in streptozotocin (STZ) - induced diabetic rats. Methods. Forty male Wistar rats were randomly divided into five groups: control, diabetic, MT 5 mg/kg+ STZ, MT 10 mg/kg+ STZ and MT 20 mg/kg+ STZ. STZ (60 mg/kg) was intraperitoneally (ip) injected as a single dose for diabetes induction. One week after STZ administration, MT was injected daily as ip for 14 days. The levels of malondialdehyde (MDA), total thiol and glutathione, as well as superoxide dismutase (SOD) and catalase activities were measured in gastric tissue. Serum concentrations of triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) were also determined. Results. Serum glucose significantly increased in diabetic group compared to control group. STZ induced a significant decrease in gastric tissue levels of total thiol, glutathione, catalase and SOD activities and a significant increase in MDA concentration. In diabetic rats, serum TG, LDL and TC were significantly higher and HDL was significantly lower than in the control group. Treatment of diabetic rats with MT caused a significant increase in gastric total thiol content and glutathione concentration as well as SOD and catalase activities. Gastric MDA concentration and serum LDL, TG and TC were significantly lower in MTtreated groups when compared with diabetic group. Conclusion. These data suggested that MT has a therapeutic effect on gastric oxidative damage and dyslipidemia induced by diabetes that possibly may be due to its antioxidant effects.

Context. Impaired flow mediated dilatation (FMD) and increased carotid intima media thickness (CIMT) are the antecedent forms of atherosclerosis. Objective. The aim of this study was to evaluate vascular structural and functional changes in patients with asymptomatic primary hyperparathyroidism (APHPT), and whether biochemical alterations, related with PHPT and oxidative stress marker serum advanced oxidation protein products (AOPPs), may have influence on vascular alterations. Design. This is a cross sectional clinical study. Subject and Methods: Thirty-four patients with APHPT and 29 sex- and age and cardiovascular risk factors matched control cases were included in this study. Endothelial function was evaluated by FMD of the brachial artery; CIMT was measured by ultrasonography; in addition serum AOPPs and biochemical parameters were determined. Results. Serum Ca levels were higher in the patient group [10.93±0.60mg/dL vs. 9.45±0.31; p<0.001]. FMD measurement was significantly lower in patients group [0.07 (0.01-0.26) % vs. 0.14 (0.04-0.22) %; p=0.01]. CIMT measurements were comparable between the groups [52 (35- 69) mm vs. 56 (38-70) mm; p=0.821]. AOPPs levels were significantly higher in the patients [136.43 (55.14-1352) mmol/L vs. 84 (53.18-595.48) mmol/L; p=0.026]. There were significant negative correlations between FMD and serum Ca (r=–0.339, p<0.001); and serum AOPPs levels (r=–0.275, p<0.005). Serum Ca (p=0.007, β=–0.353) and AOPPs (p=0.024, β=–0.243) levels and hyperlipidemia (p=0.024, β=–0.288) were the predictors of FMD. Conclusions. Vascular endothelial function is impaired in patients with APHPT. Hypercalcemia, increased oxidative stress and hyperlipidemia may have role in the pathogenesis of endothelial dysfunction in patients with APHPT.