ACTA ENDOCRINOLOGICA (BUC)

Context. Different polymorphisms of the endothelial nitric oxide synthase gene (NOS3) have been related to diabetic kidney disease. Objective. To evaluate the association between advanced diabetic chronic kidney disease (ACKD) and the rs1799983 and rs2070744 poymorphisms of NOS3 in a population from the Gran Canaria island. Design. Cross-sectional case-control study. Subjects and methods. Polymorphisms were genotyped in 152 subjects with ACKD secondary to type 2 diabetes [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2], 110 subjects with type 2 diabetes for 20 or more years since diagnosis without ACKD (eGFR ≥45 mL/ min/1.73m2 and albumin/creatinine ratio <300 mg/g and/or 24-h urinary albumin excretion <300 mg) and 292 healthy controls. Association between both polymorphisms and established coronary heart disease (CHD) was also analyzed in both groups with diabetes. Results. A greater proportion of homozygous individuals for the risk allele C of rs2070744 was found among subjects with ACKD. Association between ACKD and rs2070744 was observed in a recessive genetic model, both for comparison to subjects with diabetes but no ACKD [OR 2.17 (95% CI: 1.17-4.00), p=0.014] and for comparison to healthy controls [OR 1.61 (1.03-2.52), p=0.036]. The frequency of the C allele was significantly higher among subjects with CHD, but only in the group with ACKD. No associations were found for rs1799983. Conclusions. NOS3 rs2070744 is associated with ACKD in population with type 2 diabetes from Gran Canaria. A link between this genetic variant and CHD in Canarian subjects with type 2 diabetes could be restricted to cases with ACKD.

Background. The research evidence have suggested that ghrelin, a neuropeptide containing 28 amino acids, plays an\r\nimportant role in glucose homeostasis and its concentration is increased in diabetes.\r\nObjective. To investigate the relationship between the serum levels of ghrelin, insulin, fasting glucose and glycated hemoglobin in patients with type 2 diabetes mellitus.\r\nMaterials and Methods. Fasting glucose, insulin, ghrelin and glycated hemoglobin were measured after a 12-14 hours overnight fasting in 48 adult males with type 2 diabeties. Pearson correlations were used to establish the relationship\r\nbetween ghrelin concentration and other variables. P-value of less than 0.05 was considered statistically significant.\r\nResults. There were no correlations between serum ghrelin and Systolic and diastole blood pressure and body mass index (p<0.05). Serum ghrelin is weakly associated with glycated hemoglobin (p=0.076, R=0.19). Serum ghrelin concentrations were positively correlated with fasting glucose (p=0.005, R=0.40). In addition, ghrelin correlated negatively with\r\nserum insulin (p=0.013, r=-0.36).\r\nConclusion. Our data demonstrate that high ghrelin concentration is accompanied with increase in blood glucose\r\nin type 2 diabetic patients, and support this hypothesis that this neuropeptide plays a pathophysiological role in this disease.

Introduction: During the past thirty years bone biopsy has been used as an invasive diagnostic and research investigation of bone structure and metabolism. Quantitative bone histomorphometry parameters offer information on both bone mass and bone quality.\r\nObjectives: This study aimed to establish the value of routine qualitative bone biopsy evaluation in subjects with unexplained primary osteoporosis. Patients in whom low bone mineral density was not adequately explained by risk factors or patients in whom therapy\r\nwas not followed by BMD changes according to evidence-based data on treatment of osteoporosis were referred to bone biopsy. One-hundred seventy patients (73 men and 97 women), aged 54.29?0.95 years, were included in the study. The diagnosis was based on clinical data, lumbar spine and hip dual X-ray absorptiometry (DXA) evaluation and routine laboratory measurements. Bone biopsy was performed by horizontal approach, using an electric drill. Qualitative bone biopsy evaluation was performed in one single department by trained pathologists. Quantitative bone histology assessment (histomorphometry) was not available.\r\nResults: Of the 170 bone samples, secondary causes of low bone mineral density were identified in 19 patients (mastocytosis, multiple myeloma, myeloproliferative syndrome, sarcoidosis and osteomalacia). In 21 subjects with osteoporosis as defined by WHO criteria qualitative histological evaluation found no pathological changes. Accelerated bone resorption as expressed by the daily urinary levels of deoxypyridinoline (D-Pyr) and longterm sodium fluoride therapy were associated with relevant osteoidosis as assessed by qualitative evaluation of bone samples. Bone biopsy changes were not related to serum thyroid hormone, parathyroid hormone or 25-hydroxyvitamin D3 levels.\r\nConclusions: Qualitative bone biopsy evaluation may offer valuable information in the diagnosis of metabolic bone diseases in subjects with unexplained causes of low bone mineral density or in non-responders to anti-fracture agents. Despite of lack of quantitative information on bone mass and the degree of mineralization of bone tissue, few patients with osteoporosis may benefit from this diagnostic routine procedure.

Purpose. To correlate the volume of parathyroid adenomas with the hormonal and metabolic profile at patients diagnosed with primary hyperparathyroidism (pHPTH). Patients and Methods. Cross-sectional multicentric study, enrolling 52 patients with pHPTH from two medical institutions. Serum calcium and PTH were evaluated in all patients before surgery, whereas 25OHD3 was measured only in the 33 patients recruited form one medical unit. The volume of parathyroid adenoma was measured by using the formula of a rotating ellipsoid. Results. We observed a significant correlation of the volume of parathyroid adenomas with PTH at patients from the two units and in the whole group (p < 0.0001), but not with serum calcium (p = 0.494). Twenty-five out of the 33 patients at whom 25OHD3 was measured had levels in the range of deficiency. 25OHD3 was not correlated with PTH or calcium levels, but was negatively correlated to the adenoma volume and positively to the PTH/volume ratio (p = 0.041 and p = 0.048, respectively). Conclusions. The volume of parathyroid adenoma seems to be related to preoperative PTH and 25OHD3, but not to calcium level. Vitamin D deficiency is frequently found at patients with pHPTH and may contribute to particular disease profiles, including larger parathyroid adenomas.

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. Both human immunodeficiency virus (HIV) infection and hepatitis C virus (HCV) infection represent systemic diseases that may develop metabolic complications, thus HIV/HCV coinfection metabolic changes need to be depicted. Objective. We aimed to evaluate the body composition changes in patients with either HIV and HCV monoinfections or HIV/HCV coinfection. Methods. 123 young men divided into three groups: 41 with HIV/HCV coinfection, 42 with HIV-monoinfection, and 40 with HCV-monoinfection were evaluated for total and regional bone and soft tissue body composition assessments using a Dual-energy X-ray absorptiometry (DXA) and were compared with 40 healthy men with age and body mass index similar to the study groups. To detect sarcopenia, we calculated the appendicular limbs’ lean mass index (ALMI), for obesity, we used the percent of body fat, and for lipodystrophy, we calculated the trunk/limbs index. Results. HIV/HCV coinfection is associated with a significant higher bone demineralization in all regions of interest compared to HCV or HIV monoinfections and to controls. The prevalence of bone demineralization in HIV/ HCV patients was 31.7%, more frequently at lumbar spine. Fat mass and lean mass were significantly lower in HIV/ HCV-coinfected patients than in controls. Lipodystrophy was found in similar percentages in all three evaluated groups (80.4% in HIV/HCV, 92.5% in HIV, and 95% in the HCV group). Sarcopenia was higher in HIV/HCV group (43.9%) and important in HCV-monoinfection group (30%). Conclusions. HIV/HCV-coinfected patients had the highest prevalence of bone demineralization, fat mass, and lean mass loss, compared to controls and to HIV and HCV monoinfections.

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.

Background. Insulin degludec/aspart (IDegAsp) is a co-formulation with IDeg and IAsp. Different insulin regimens may be switched to IDegAsp. In this study, we aimed to find out the effect of switch to IDegAsp on glycemic control and whether the basal characteristics and treatment modalities of the patients affect the change in glycemic control brought by switch to IDegAsp. Methods. We retrospectively analyzed the records of 78 patients whose insulin therapies (basal+bolus, premixed analogues or basal only) were switched on a 1:1 unit basis to IDegAsp±bolus insulin. Oral antidiabetic agents (OADs) given were recorded. At the end of 12th and 24th week, total insulin doses of patients and HbA1c were compared to the baseline. Results. There was a statistically significant decrease at HbA1c at 12 weeks (1.4%; p<0.001). There was not a significant difference in HbA1c between the OAD added group and the group with no new OADs(p=0.1). Basal insulin dose was not statistically different from baseline, whereas bolus insulin dose was significantly lower (p=0.007). At the end of 24 weeks the decrease in HbA1c level from baseline was preserved. Conclusion. Regardless of the baseline insulin regimen, diabetes type and oral antidiabetic drugs given, HbA1c is significantly lowered after switching to IDegAsp.

Our aim was to explore the interactions of intercellular adhesion molecule (sICAM-1), TNF-&#945; (tumor necrosis factor-&#945;), interleukin-1&#945; (IL-1&#945;) and interleukin-6 (IL-6) with\r\ndopamine agonists in a culture of adenomatous cells from an nonfunctional macroadenoma.\r\nMaterials and methods. Tissue specimen from pituitary macroadenoma removed in transsphenoidal surgery was prepared for primary culture. Cells were counted and plated at 105/well into 24-well plates in a final volume of 1ml. Cabergoline in molar doses of 10-6, 10-7, 10-8, 10-9 was added and the cells were incubated for 4 days. sICAM-1, TNF-&#945;, IL-1&#945;, IL-6 were measured from cell-culture supernatants by ELISA kits.\r\nResults. sICAM-1, TNF-&#945;, IL-1&#945; and IL-6 were detected in the untreated control cultures after a 4d period. There was a negative correlation between TNF&#945; and IL-1&#945; (p=0.007).\r\nThe levels of PRL and hGH had measurable values above those found in culture medium without tumor cells. PRL positively correlated with IL-1&#945; ( p=0.05). hGH positively correlated with cell proliferation (p=0.049). Cabergoline treatment showed that IL-6 progressively decreased with the dose, ranging from -27.41% to -76.44%. TNF-&#945; significantly decreased (-65.90%; p<0.03)at the cabergoline 10-7 M dose. IL-1&#945; progressively increased with cabergoline dose, ranging\r\nfrom -2.53% to 345 %. sICAM-1 was significantly reduced by cabergoline at 10-9 (-47.12 %; p=0.045) and 10-6 M (-59.16%; p=0.01) doses. TNF-&#945; positively correlated with PRL (p=0.025); IL-6 positively correlated with hGH (p=0.044); sICAM-1 negatively correlated with hGH\r\n(p=0.009), TNF&#945; (p=0.025) and IL-1&#945; (p=0.044).\r\nConclusions. These data support the existence of an immunoendocrine network in pituitary tumorigenesis; TNF-&#945;, IL-6, IL-1&#945;, sICAM-1 significantly interfered by cabergoline\r\ntreatment in a dose-dependent way. However, future studies on different types of pituitary tumours are needed to confirm these findings.

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.