Maternal Serum Copper and Some Metabolic Indexes in Late Second Trimester of Gestational Diabetes Mellitus Pregnancy.

BACKGROUND: Copper (Cu) is a physiologically important trace element during pregnancy. The study aim is to assess the altered level of serum Cu and its association with some metabolic indexes in Gestational Diabetes Mellitus (GDM). METHODS: A total of 108 pregnant women (aged 18 - 40, second trimester) are included in the study and divided into two groups (GDM n = 54; pregnant with normal glucose tolerance (NGT), n = 54) after performing a 2-hour 75-g oral glucose tolerance test (OGTT). Maternal blood samples are collected at 26 - 28 gestational week. All biochemical parameters are measured in serum from fasting venous blood. Serum Cu levels are analyzed by flame atomic absorption spectrophotometry (Perkin Elmer AAnalyst 300, USA). Body Mass Index (BMI), insulin sensitivity/resistance, triglyceride-glucose (TyG), TyG-BMI (triglyceride glucose-body mass) indexes are calculated by formulas. RESULTS: The following data were observed: significantly higher levels of serum Cu (p = 0.009), pre-pregnancy BMI (pre-pBMI), BMI at the GDM diagnosis (pBMI), TyG, pregnancy TyG-BMI (pTyG-BMI) p < 0.001, and triglycerides (Tgl) (p = 0.02) in GDM compared to NGT pregnancy. The study presents a positive correlation between serum Cu and pre-pBMI (p < 0.02), pBMI and pTyG-BMI (p < 0.001). Besides, pre-pBMI (mean ≥ 25 kg/m2), pBMI (mean ≥ 30 kg/m2), and pTyG-BMI are associated with 14.5% (OR 1.145, 95% CI: 1.064 - 1.232; p < 0.001), 15.3% (OR 1.153, 95% CI: 1.070 - 1.243; p < 0.001), and 5.9% (OR 1.059, 95% CI: 1.022 - 1.086; p < 0.001) increased risk for GDM development. No association is found between Cu and Tgl levels, fasting plasma glucose e(FPG) and TyG. ROC analysis suggests the serum Cu as a possible risk factor for GDM development. The analysis shows that at a cutoff point of ≥ 31.9 µmol/L, serum Cu presents a sensitivity and specificity of 64.8% and 66.7% in the prediction of GDM development (AUC = 0.659, p < 0.012). After adjustment for maternal age, gestational age, and family predisposition, the odds ratios (ORs) (95% CIs) still show association of Cu levels with increased GDM risk (OR 1.099, 95% CI 1.018 - 1.184, p = 0.013). CONCLUSIONS: pTyG-BMI index exhibits a better interaction than TyG index, Tgl, and glucose separately with serum Cu levels where BMI has a mediator's role.

Evaluation of zinc, copper, and Cu:Zn ratio in serum, and their implications in the course of COVID-19.

BACKGROUND: The dynamics of essential metals such as Copper (Cu) and Zinc (Zn) may be associated with the novel coronavirus disease 2019 (COVID-19) that has spread across the globe. OBJECTIVES: The aim of this study is to investigate the relationship between serum levels of Cu and Zn, as well as the Cu:Zn ratio in the acute phase of COVID-19 along with the assessment of their connection to other laboratory parameters (hematological, biochemical, hemostatic). METHODS: Serum levels of Cu and Zn were measured by atomic absorption spectrometry in 75 patients in the acute COVID-19 phase and were compared with those of 22 COVID-19 patients evaluated three months after the acute phase of the disease ('non-acute' group) and with those of 68 healthy individuals. RESULTS: In comparison with both the non-acute patients and the healthy controls, the acute patients had lower levels of hemoglobulin and albumin, and higher levels of glucose, creatinine, liver transaminases, C-reactive protein (CRP), and higher values of the neutrophils to lymphocytes ratio (NLR) at the hospital admission. They also exhibited increased levels of Cu and decreased of Zn, well represented by the Cu:Zn ratio which was higher in the acute patients than in both non-acute patients (p = 0.001) and healthy controls (p < 0.001), with no statistical difference between the last two groups. The Cu:Zn ratio (log scale) positively correlated with CRP (log scale; r = 0.581, p < 0.001) and NLR (r = 0.436, p = 0.003). CONCLUSION: Current results demonstrate that abnormal dynamics of Cu and Zn levels in serum occur early during the course of COVID-19 disease, and are mainly associated with the inflammation response.

Serum hepcidin levels in Bulgarian population.

BACKGROUND: Hepcidin is a 25-aminoacid cysteine-rich iron regulating peptide. Hepcidin quantification in human serum provides new insights for the pathogenesis of disorders of iron homeostasis. This study describes an ELISA immunoassay for hepcidin quantification in human serum and reference ranges for Bulgarian population. METHODS: We used a sandwich ELISA method from USCN Life Science inc. that consists of ready to use, pre-coated 96-well strip plate with 2 antihepcidin-25 monoclonal antibodies. A recombinant Hepcidin in 16 µg/L concentration is used as a standard. We correlated ELISA results of hepcidin-25 measurements in healthy population to ferritin, hemoglobin concentration in reticulocytes, transferrin, and iron levels. RESULTS: The sandwich ELISA was highly specific for hepcidin-25. We found that serum hepcidin levels for Bulgarian population are 3.052 µg/L - 37.750 µg/L, which is quite similar to that established by WCX-TOF MS from the Laboratory of Genetic, Endocrine and Metabolic Diseases; Dept. of Laboratory Medicine, Radbound University Medical Centre; Nijmegen, The Netherlands. Ferritin levels and hemoglobin concentration in reticulocytes correlated significantly to serum hepcidin levels (0.3 < r < 0.5, p < 0.010). Transferrin levels showed negative and no significant correlation to hepcidin in serum (r = -0.111). CONCLUSIONS: The use of two monoclonal antibodies in a sandwich ELISA format provides a reliable, reproducible, and not very expensive method for measuring serum concentrations of the bioactive form of hepcidin in Bulgarian laboratory practice.

Duodenal ascorbate and ferric reductase in human iron deficiency.

BACKGROUND: The first step in iron absorption requires the reduction of ferric iron to ferrous iron, a change that is catalyzed by duodenal ferric reductase. Iron deficiency is associated with high iron absorption, high ferric reductase activity, and high duodenal ascorbate concentrations in experimental animals, but it is not known whether a relation between reductase and ascorbate is evident in humans. OBJECTIVE: The objective of the study was to assess the relation between ferric reductase activity in human duodenal biopsy specimens and ascorbate concentrations in iron-replete and iron-deficient subjects. DESIGN: Patients and control subjects were overnight-fasted adults presenting sequentially for upper gastrointestinal endoscopic investigation. Ferric reductase activity in duodenal biopsy specimens was assayed by using nitroblue tetrazolium. Ascorbate was assayed in duodenal biopsy specimens and plasma. RESULTS: Iron-deficient patients had significantly higher reductase activity (n = 6-9; P < 0.05) and duodenal (n = 20; P < 0.001) and plasma (n = 6; P < 0.001) ascorbate concentrations than did control subjects. Incubation of biopsy specimens with dehydroascorbate (to boost cellular ascorbate) increased reductase activity in the tissues that initially had normal activity (n = 9; P < 0.01) but inhibited reductase activity in the tissues that already had high reductase activity (n = 13; P < 0.001). CONCLUSIONS: Iron deficiency in humans is associated with increased duodenal ascorbate concentrations. This finding suggests that increased reductase activity is partly due to an increase in this substrate for duodenal cytochrome b reductase 1.

Duodenal ascorbate levels are changed in mice with altered iron metabolism.

Ascorbate has long been thought to play an important role in intestinal iron absorption. The recent identification of a possible ascorbate-dependent duodenal ferric reductase suggests a role for intracellular ascorbate in the control of iron absorption. We set out to determine whether duodenal ascorbate concentrations are altered by treatments known to alter the rate of iron absorption and whether ascorbate levels affect duodenal reductase activity. Duodenal ascorbate was extracted and assayed by HPLC and/or a chemical assay. Ferric reductase was assayed in vitro with ferric nitrilotriacetate or nitroblue tetrazolium as substrates. Duodenal ascorbate concentrations were increased by iron deficiency, genetic hypotransferrinemia, and hypoxia. Parenteral iron overload increased iron stores but did not affect duodenal ascorbate concentrations. Hemolytic anemia induced in mice by phenylhydrazine injection also did not affect duodenal ascorbate concentrations. In vitro studies with incubated duodenum showed that decreased tissue ascorbate was associated with decreased mucosal ferric reductase activity, whereas incubation with dehydroascorbate prevented both the decrease in ascorbate concentration and reductase activity. Mouse duodenum ascorbate concentrations changed in response to treatments that altered iron absorption rates; in particular, ascorbate levels generally increased when iron absorption was increased by iron deficiency, hypoxia, or genetic hypotransferrinemia. We conclude that changes in ascorbate levels are associated with changes in ferric reductase activity. These findings are consistent with the proposal that duodenal ascorbate plays a role in intestinal iron absorption.