ACTA ENDOCRINOLOGICA (BUC)

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.

A number of recent studies in animals and humans have linked energy regulation and the circadian clock at the molecular, physiological and behavioural levels, concluding that disruption of clock genes results in metabolic dysregulation. The search to understand the causes of obesity and diabetes and the development of new therapeutic strategies have mostly focused on caloric intake and energy balance. In this review, we present a global overview of the circadian clock as a critical interface between nutrition and homeostasis.

Context. Cholelithiasis in childhood is uncommon, while in infancy it is rarely reported. An extremely rare form of cholelithiasis occurs with pseudohypoaldosteronism (PHA). In these patients gallstone formation has been attributed to dehydration and salt-wasting, starting from fetal life. Case report. A neonate with PHA presented with dystrophy, vomiting, hyponatraemia, hyperkalaemia, metabolic acidosis and gallstone formation. Plasma renin activity and aldosterone concentrations were elevated and urinary Na excretion was increased. Gallstones automatically subsided at the age of six months after appropriate sodium chloride supplementation. Conclusions. Infants with PHA , even without signs of salt wasting, should be investigated for cholelithiasis. Inversely, in infants with pertinent electrolyte abnormalities and cholelithiasis, PHA should be considered among the possible diagnoses.

Context. Subacute thyroiditis (SAT) is an inflammatory disease of the thyroid gland and commonly affects females. Despite adequate treatment, the recurrence of SAT can be seen in some patients. Although there is insufficient data about the reasons for recurrences, HLA predisposition is one of the reasons thought to be responsible and is a current issue for clinicians. Objective. This case report presented the management of 7 SAT attacks of a patient who had HLA-B35:01 and B41:02 alleles in the genotype analysis. Case Report. A 37-year-old male patient who had consecutive 7 SAT attacks was presented in this report. Corticosteroid or non-steroidal anti-inflammatory drugs were initiated at each recurrence depending on the severity of clinical symptoms and laboratory findings. The genotype analysis showed the positivity for HLA-B35:01 and B41:02 alleles. The anti-thyroglobulin antibody was detected positive after the last attack. The patient was followed up as asymptomatic and euthyroid in the third month after the last attack. Results. The management of some SAT cases may be challenging for clinicians. Although recurrence can be seen despite adequate treatment, repetitive seven attacks are extraordinary in SAT. HLA genotyping showed cooccurrence of HLA-B35:01 and B41:02 alleles in our patient. The co-occurrence of these alleles has been described firstly in this case. Explaining high recurrence rates of SAT with these HLA alleles is difficult, though the present case may shed light on further studies.