Trace elements in diabetes mellitus. Peculiarities and clinical validity of determinations in blood cells

Significantly more information about trace element status can be obtained by investigating concentrations in blood cells instead of only evaluating the concentrations in plasma. This can be explained by the fact that essential trace elements such as zinc, copper, chromium and selenium take part in a variety of enzymatic processes on a molecular cellular level. Ignoring these important biochemical roles, trace element concentrations determined in whole blood or plasma very often lead to conclusions contrary to the actual intracellular concentration. Especially in metabolic diseases like diabetes mellitus, conclusions drawn from trace element concentrations in blood cells usually offer more valuable clinical information about the metabolic state than trace element concentrations in plasma or whole blood. In the present investigation copper and zinc concentrations were increased in all blood fractions of diabetic patients (IDDM). In insulin-dependent diabetic children significantly higher values of zinc in erythrocytes were also found, and they were higher in patients with poor metabolic control (HbA1c>9%). When different blood fractions in diabetic patients (NIDDM) were compared with a control group, chromium was significantly increased in plasma and polymorphonuclear cells. Patients with IDDM had pronounced decreased selenium concentrations in erythrocytes as compared to controls.     

Trace mineral status in post menopausal women: impact of hormonal replacement therapy.

The risks of disturbances in trace mineral nutrition and metabolism are high following menopause. The aim of the study was to investigate the trace mineral status in postmenopausal women and the influence of hormonal replacement therapy on this status. Forty-four healthy postmenopausal women, aged 50-60 years old participated in the study. Eighteen were treated by combined hormonal replacement therapy (HRT) per os for at least two years, and 26 were untreated. Plasma trace mineral levels (Zn, Se, Cr, Mn, Cu), red blood cell antioxidant enzymes (Cu-Zn SOD, Se-GPX, Cu), urinary Zn, Cr, Mg, and Ca excretion were measured. Zinc, selenium and manganese plasma levels, activities of Cu-Zn-SOD and GSH-Px in erythrocytes were not statistically different between the two groups. The percentage of zinc plasma levels below the cut off of 10.7 micromol/L was higher in HRT treated group than in untreated one, whereas zinc excretion was reduced. Plasma copper concentrations were higher in women treated by HRT, whereas erythrocyte copper levels were not modified. Plasma chromium concentrations were significantly higher in women receiving HRT and urinary Cr excretion was decreased. The HRT group also exhibited lower losses of urinary zinc and magnesium than untreated women. These data suggest that hormonal replacement therapy provides beneficial effects on trace mineral status related to menopause.     

Effects of halothane, enflurane, and isoflurane on plasma and erythrocyte antioxidant enzymes and trace elements

Alterations of the normal redox balance in mammals might be attributed to increases of plasma free-radical concentrations and/or a disruption of the protective mechanisms. These conditions lead to damage to cellular structure by the mechanism of lipoperoxidation, particularly in the liver, kidney, and central nervous system. In this study, the effect of general anesthesia on the oxidative metabolism of human plasma and erythrocytes was investigated. Forty-five patients undergoing anesthesia by using halothane, enflurane, or isoflurane were included in this study. Blood samples were taken preoperatively, the first hour, the first day, and the third day after the operation. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities and trace elements such as cofactor copper (Cu), zinc (Zn) and selenium (Se) levels were measured in plasma and red blood cells. Our results showed that halothane and enflurane administration increased the plasma GSH-Px activity and reduced zinc levels. In addition, they lowered SOD and GSH-Px activities and trace element levels on erythrocytes. Isoflurane had no effect on plasma antioxidant enzymes, but, similar to the other, isoflurane decreased the plasma zinc levels, erythrocyte SOD and GSH-Px activities and trace element levels. Gülhane Military Medical Academy     

Lipid peroxidation and antioxidant system in the blood of cancerous patients with metastasis

Free-radical-mediated damages may play an important role during metastasis. To investigate their relevance in the metastatic process MDA levels, glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities, and selenium, zinc and copper contents were determined in plasma and erythrocytes from 20 cancerous patients with metastasis and 30 age-matched controls. Significantly higher concentrations of MDA in plasma as well as in erythrocytes were found comparing to the control group. In both plasma and erythrocytes, GPX activity and selenium and zinc levels were significantly lower in patients than in controls. However, SOD activity in erythrocytes and copper levels in both plasma and erythrocytes were significantly higher in patients. The impaired antioxidant system may favor accumulation of free radicals which may induce the process of metastasis. On the other hand, it is possible that the antioxidant system is impaired as a consequence of abnormality in the antioxidative metabolisms due to the cancer process.     

Trace elements status in multinodular goiter

Importance of iodine and selenium in thyroid metabolism is well known, but the roles of other essential trace elements including copper, zinc, manganese and iron on thyroid hormone homeostasis remain unclear. The aim of this study was to investigate the status of those trace elements in benign thyroid diseases and evaluate possible links between trace element concentrations and thyroid hormones.The study group was composed of 25 patients with multinodular goiter. Concentrations of thyroid hormones (plasma-free thyroxine, FT₄; free triiodothyronine, FT₃; and thyrotropin, TSH), selenium, copper, zinc, manganese and iron in plasma, and urinary iodine were determined. The results were compared with those of a healthy control group (n=20) with no thyroid disorder.A mild iodine deficiency was observed in the patients with multinodular goiter whereas urinary iodine levels were in the range of “normal” values in healthy controls. All patients were euthyroid, and their thyroid hormone concentrations were not significantly different from the control group. Plasma selenium, zinc and iron concentrations did not differ from controls, while copper and manganese levels were found to be significantly higher in the patients with multinodular goiter indicating links between these trace elements and thyroid function and possibly in development of goiter. Besides iodine, there was a significant correlation between plasma copper concentration and FT₃/FT₄ ratio.     

Evaluation of superoxide dismutase and glutathione peroxidase enzymes and their cofactors in Egyptian children with Down's syndrome

The present work investigated the activity of Cu/Zn superoxide dismutase enzyme (SOD) in red blood cells and glutathione peroxidase enzyme (GPx) in whole blood by spectrophotometric methods. Plasma levels of the cofactors copper and zinc and whole-blood selenium were evaluated using atomic absorption spectrophotometer. The study included a population of 18 Down's syndrome (DS) patients with complete trisomy 21 (group 1), translocations (group 2), and mosaicism (group 3), and their 15 matched controls. The purpose of this work was to study the gene dosage effect of SOD and its consequence on GPx enzyme and the various cofactors, and to find out correlations with developmental fields. Our results showed that in the population with complete trisomy 21 and translocations, SOD and GPx activities were increased, whereas in cases with mosaicism, the enzymes activities were within normal limits. Plasma copper concentrations were increased, whereas whole-blood selenium concentrations were significantly decreased in the three DS groups. Plasma zinc levels were within normal in all patients. We concluded that changes in trace elements and enzyme activities were not related to age or sex. Also, there was no correlation between the enzyme levels and the developmental activities. Our results are useful tools for identifying nutritional status and guiding antioxidant intervention.     

Associations among plasma selenium,zinc, copper,and iron concentrations and immunoregulatory cytokine levels in patients with cutaneous leishmaniasis

Plasma essential trace elements, selenium, copper, zinc, and iron concentrations and the levels of immunoregulatory cytokines, interleukin-1β (IL-1β), interleukin-2 receptor (IL-2r), IL-6, IL-8, and tumor necrosis factor-α (TNF-α) were evaluated in patients with cutaneous leishmaniasis (CL) to investigate a possible role of these cytokines on selenium, zinc, copper, and iron homeostasis in CL patients. Plasma albumin levels were measured as an index of nutritional status. Plasma selenium, zinc, and iron concentrations, and IL-2r levels were significantly lower, and copper concentrations and IL-1β, IL-8, IL-6 and TNF-α levels were significantly higher in patients with CL than those of healthy controls. There was no significant difference in plasma albumin levels between two groups. There were positive important correlations between plasma selenium and IL-2r, copper and IL-6, and copper and IL-1β, and negative correlations between selenium and IL-8, iron and TNF-α, and zinc and IL-1β contents in patients with CL. Our results showed that plasma trace element contents change in patients with CL. These changes may not be a result of a specific deficiency from dietary inadequacies or imbalances, but, probably, a result of a part of the defense strategies of an organism that is regulated by immunoregulatory cytokines.     

Altered Plasma Concentrations of Trace Elements in Ulcerative Colitis Patients Before and After Surgery

Ileal pouch-anal anastomosis (IPAA) is a classical surgery for ulcerative colitis patients. However, knowledge on trace element alteration in patients who had undergone this surgery is limited. This study was conducted to assess trace element alteration in patients with ulcerative colitis before and after ileal pouch-anal anastomosis. Preoperative (40) and postoperative (35) ulcerative colitis patients were studied. The dietary assessment of trace element intake was undertaken by a semiquantitative food frequency questionnaire. Patients' trace element status of zinc, copper, manganese, selenium, calcium, iron, and vitamin D₃ was assessed by measuring their blood concentrations. We found that with the similar dietary intake, there was no statistical difference in the concentrations of plasma copper, iron, calcium, and vitamin D₃ in the two groups (P?>?0.05). Compared with preoperative patients, postoperative patients had higher concentrations of plasma zinc (14.51?±?4.75 μmol/l) and manganese (0.21?±?0.11 μmol/l) and lower concentrations of plasma selenium (0.86?±?0.58 μmol/l). Both preoperative and postoperative mean concentrations of plasma calcium and vitamin D₃ were below their reference range, respectively. We conclude that IPAA does not seem to alter patients' abnormal trace elements completely. It is important to monitor and supply some specified trace elements even in postoperative patients.     

Effects of Multivitamin/Mineral Supplementation on Trace Element Levels in Serum and Follicular Fluid of Women Undergoing in Vitro Fertilization (IVF)

We investigated effects of multivitamin/mineral supplementation on element levels in serum and follicular fluid of women undergoing IVF. We used three groups in this study. The first group was used as an age-matched and nonpregnant control (n = 13). Group 2 (n = 30) constituted the IVF group and women in the third group who were undergoing IVF also received a multivitamin/mineral tablet daily for 45 days. Follicular fluid and serum selenium and zinc levels and follicular fluid copper levels were lower in IVF patients than in controls although follicular fluid aluminum and iron levels were higher in IVF patients than in controls. However, follicular fluid and serum aluminum, copper, zinc and selenium levels, and serum magnesium levels were higher in the multivitamin/mineral group than in the IVF group although follicular fluid iron levels were lower in the multivitamin/mineral group than in the IVF group. In conclusion, we observed that copper, zinc, and selenium in serum and follicular fluid decreased in women undergoing IVF. Multivitamin/mineral supplementation in serum and follicular fluid of women undergoing IVF normalized the trace element levels.     

Trace elements and melanoma.

Melanoma incidence has been steadily increasing in recent years in most western countries, thus suggesting a role of environmental risk factors. Among these determinants, it has been hypothesized that some trace elements of nutritional and toxicological interest may be implicated in the etiology of the disease. We examined patients with newly diagnosed melanoma of the skin and population controls from the Modena province northern Italy. Clinical and dietary data were collected through questionnaires, and toenails were sampled for trace element determination. Levels of cadmium, chromium, lead, selenium, zinc, copper and iron in toenails were measured by inductively coupled plasma optical emission spectrometry and by neutron activation analysis. Data obtained from 58 cases and 58 controls indicated higher levels of copper and lower concentrations of iron in melanoma patients, whilst no other differences were seen for the remaining elements. Patterns of correlations of zinc and copper with the estimated intake of some dietary factors were different between cases and controls. Results of the present study suggest that abnormal intake or metabolism of copper and of iron might be implicated in the etiology of melanoma, whilst they do not indicate an involvement of exposure to cadmium, chromium, lead, selenium and zinc in this disease.     

Trace Element Distribution in Selected Edible Tissues of Zebu (Bos indicus) Cattle Slaughtered at Jimma,SW Ethiopia

The amount of trace elements present in edible bovine tissues is of importance for both animal health and human nutrition. This study presents data on trace element concentrations in semitendinosus and cardiac muscles, livers and kidneys of 60 zebu (Bos indicus) bulls, sampled at Jimma, Ethiopia. From 28 of these bulls, blood samples were also obtained. Deficient levels of copper were found in plasma, livers, kidneys and semitendinosus muscles. Suboptimal selenium concentrations were found in plasma and semitendinosus muscles. Semitendinosus muscles contained high iron concentrations. Trace elements were mainly stored in the liver, except for iron and selenium. Cardiac muscles generally contained higher concentrations of trace elements than semitendinous muscles except for zinc. A strong association was found between liver and kidney concentrations of copper, iron, cobalt and molybdenum. Liver storage was well correlated with storage in semitendinosus muscle for selenium and with cardiac muscle for cobalt and selenium. Plasma concentrations of copper, selenium, cobalt were well related with their respective liver concentrations and for cobalt and selenium, also with cardiac muscle concentrations. The data suggest multiple trace element deficiencies in zebu cattle in South-West Ethiopia, with lowered tissue concentrations as a consequence. Based on the comparison of our data with other literature, trace element concentrations in selected edible tissues of Bos indicus seem quite similar to those in Bos taurus. However, tissue threshold values for deficiency in Bos taurus cattle need to be refined and their applicability for Bos indicus cattle needs to be evaluated.     

Trace element status in Saudi patients with established atherosclerosis

BACKGROUND: Traditional coronary risk factors do not fully explain variations in the incidence of cardiovascular disease (CVD). Epidemiological studies have implicated perturbations in selenium, copper, and zinc metabolism in the aetiology of CVD. However, these studies have been principally undertaken in Caucasian populations, in whom trace element intake is generally sufficient. METHOD: We have measured serum and urine selenium, copper, and zinc; and superoxide dismutase, glutathione peroxidase, and lipid peroxide concentrations in 130 Saudi male subjects with established CVD, and 130 age-matched controls. RESULTS: Diabetes mellitus, positive smoking habit (p<0.0001 for both), and hypertension (p<0.05) were more prevalent among CVD patients. Urinary copper (p<0.0001) and zinc (p<0.05) were higher among controls. Serum selenium concentrations were lower among CVD patients (p<0.001), and a high proportion (52%) had selenium levels below 79mug/L compared to controls (22%) (p<0.0001). Conditional logistic regression analysis, showed the characteristics differentiating CVD patients from controls were serum zinc (odds ratio (OR) 0.92, confidence interval (CI) 0.85-0.99, p<0.05), serum copper/zinc ratio (OR 0.31, CI 0.10-0.96), serum selenium (OR 0.07, CI 0.02-0.31, p<0.0001), and urine selenium (OR 3.34, CI 1.40-7.99, p<0.01). CONCLUSION: Measures of trace metals status appear to be associated with the risk of atherosclerosis in a Saudi male population.     

不育男性患者和健康男性血液与精浆中微量元素含量的对比分析

目的:研究不育患者精浆和血液中微量元素的含量,为男性不育的诊断和治疗提供理论依据。方法:对73例正常生育组男性和265例男性不育患者的精浆和血液中的锌、铁、铜、钙、镁、镉进行检测分析,分析两组血液和精浆微量元素的差异。结果:不育组患者精浆和血液中锌的含量明显低于正常对照组,铜、镉离子含量明显高于正常对照组,与正常对照组比较均有显著性差异(P<0.01);而两组中的钙、铁、镁的含量接近,差异无统计学意义(P>0.05)。不育组患者精浆中的锌元素水平明显高于血液锌含量,而血液中的镉含量明显高于精浆中的镉含量,差异有明显的统计学意义(P<0.05)。结论:精浆和血液中锌、铜、镉的变化与男性不育密切相关。     

Concentrations of seven trace elements in different hematological matrices in patients with type 2 diabetes as compared to healthy controls

This study aimed to compare the trace element status of patients with type 2 diabetes (n=53) with those of nondiabetic healthy controls (n=50). The concentrations of seven trace elements were determined in the whole blood, blood plasma, erythrocytes, and lymphocytes of the study subjects. Vanadium and iron levels in lymphocytes were significantly higher in diabetic patients as compared to controls (p<0.05 for iron and p<0.01 for vanadium). In contrast, lower manganese (p<0.01) and selenium (p<0.01) concentrations were detected in lymphocytes derived from patients with type 2 diabetes versus healthy subjects. Furthermore, significantly lower chromium levels (p<0.05) were found in the plasma of diabetic individuals as compared to controls. Trace element concentrations were not dependent on the degree of glucose control as determined by correlation analysis between HBA_1c versus metal levels in the four blood fractions. In summary, this study primarily demonstrated that trace element levels in lymphocytes of patients with type 2 diabetes could deviate significantly from controls, whereas, in general, no considerable differences could be found when comparing the other fractions between both patient groups. Therefore, it seems reasonable to analyze metal levels in leukocytes to determine trace element status in patients with type 2 diabetes and perhaps in other diseases.     

Rapid and direct determination of selenium, copper, and zinc in blood plasma by flow injection-inductively coupled plasma-mass spectrometry

A flow injection-inductively coupled plasma-mass spectrometry (FI-ICP-MS) with a simple sample preparation procedure was developed for the determination of selenium, copper, and zinc in blood serum/plasma. A serum/plasma sample was filtered through a 0.45-μm membrane filter and diluted with a mixture of trace elements in a standard solution (9∶1, v/v). Measurement of the reference serum sample confirmed the accuracy of our method for selenium, copper, and zinc concentration. In the case of blood plasma samples obtained from six healthy adult males, the selenium, copper, and zinc concentrations were similar to those of a typical healthy male in Japan. These results suggest that the sample prepartive procedure coupled with FI-ICP-MS can be used for the routine determination of selenium, copper, and zinc in human blood serum/plasma.     

Idiopathic scoliosis and concentrations of zinc,copper, and selenium in blood plasma

The concentration of zinc, copper, selenium, albumin, and ceruloplasmin in blood plasma and the activity of superoxide dismutase and glutathione peroxidase in erythrocytes were determined in a set of patients with idiopathic scoliosis (n=51). A significant decrease of selenium concentration (0.50±0.16 μmol/L) was found when compared with a control group (0.69±0.07 μmol/L) (p<0.01). The same levels of significance were found out for selenium levels corrected for albumin content. In a group of patients with a curvature over 45° indicated for a surgical correction, the average plasma concentrations of selenium were significantly lower (p<0.05) in comparison with a group of patients with a curvature below 45° treated conservatively. The GSH-Px activity in erythrocytes was the same in both sets. In comparison with the controls, no significant differences were revealed in all of the other parameters. The detection of the decreased blood plasma concentration of selenium has suggested possible disturbance of well-proportioned distribution and of general optimal availability of selenium in the organism of patients with idiopathic scoliosis with likely effects on the process of synthesis and maturation of collagen affecting the axial skeleton stability.     

Changed serum trace element profile in Down's syndrome

Being cofactors of important antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), which are significantly modified in Down's syndrome (trisomy 21), serum levels of microtrace elements zinc, copper, and selenium and of macroelement magnesium are reported in 16 subjects with Down's syndrome (DS) and their respective well age- and sex-matched controls. Serum zinc and selenium levels were significantly lowered in DS subjects, whereas copper levels were elevated. Consequently, a marked increase (40%) of the copper/zinc ratio in DS persons was observed. There were no differences in serum levels of magnesium between DS and control subjects.     

Concentations of copper, Zinc, and magnesium in sera from patients with idiopathic dilated cardiomyopathy

Trace elements are known to have a key role in myocardial metabolism. The accumulation (cobalt, arsenic, copper) or deficiency (selenium, zinc) of trace elements may be responsible for idiopathic dilated cardiomyopathy. We investigated the trace element concentrations (Cu, Zn, Mg) in sera from patients with dilated cardiomyopathy by atomic absorption spectrophotometry. We observed that patients with dilated cardiomyopathies have higher copper and lower zinc concentrations in serum than healthy controls. The magnesium concentrations of patients did not differ significantly from that of control subjects.     

Levels of selenium, zinc, copper, and antioxidant enzyme activity in patients with leukemia

Essential elements, mainly selenium and zinc, were involved in protection against oxidative stress in cells. Oxidation could lead to the formation of free radicals that have been implicated in the pathogenesis of many diseases, including leukemia. Leukemia is a neoplastic disease that is susceptible to antioxidant enzyme and essential elements alterations. This study was undertaken to examine the levels of essential elements, antioxidant enzymes activities, and their relationships with different types of leukemia. Serum selenium, zinc, and copper concentrations, red blood cell glutathione peroxidase (GPx) activities, plasma Cu−Zn superoxide dismutase (Cu−Zn SOD) activities and lipid peroxidation (LPO) levels were determined in 49 patients with different types of leukemia before initial treatment. Serum selenium and zinc concentrations were lower in leukemia patients than those of controls (p<0.01). Serum copper concentration was higher in leukemia patients than that of controls (p<0.01). The activities GPx and Cu−Zn SOD were significantly increased in leukemia patients, especially with acute leukemia (AL), acute lymphoid leukemia (ALL), and acute nonlymphoid leukemia (ANLL) (p<0.05), whereas no difference was found between those of chronic myelogeneous leukemia and the controls. The levels of LPO were normal as controls. Serum selenium concentration was not correlated with GPx, and serum levels of zinc and copper were not related to Cu−Zn SOD. Serum zinc levels had a negative correlation with the absolute peripheral blast cells, whereas serum copper had a positive correlation with the absolute peripheral blast cells. Increased GPx and Cu−Zn SOD activities and normal levels of LPO, which were a protective responses, were an indicator of mild oxidative stress; it mights indicate that the essentials elements alterations in leukemia patients were mostly dependent on tumor activity. Changes of their levels demonstrated that there are low selenium, zinc, and high copper status in leukemia patients. The decrease of plasma zinc and increase of the Cu/Zn ratio could be the index that showed an unfavorable prognosis of acute leukemia.     

Effects of Vitamins C and E Combination on Element Levels in Blood of Smoker and Nonsmoker Radiology X-Ray Technicians

X-ray radiation is detrimental to human cells and may lead to development of life-threatening diseases. Cigarette paper and cigarette smoke contain toxic elements, whereas vitamins C and E (VCE) may have regulator effects on the elements. We investigated effects of VCE administration on X-ray-induced element changes in blood of smoker and nonsmoker X-ray technicians. Twenty technicians and 30 healthy age-matched control subjects were used in the study. Ten of the X-ray technicians and 15 of the control were smokers. Blood serum samples were taken from the control. Oral vitamins C (500 mg) and E (150 mg) were supplemented daily to the smoker and nonsmoker X-ray technicians for 5 weeks. Serum samples were taken from the X-ray technicians before and after 5 weeks. Copper, zinc, selenium, aluminum, iron, magnesium, and calcium levels were investigated in control and X-ray technicians, both smokers and nonsmokers. Copper, zinc, and selenium levels were lower in the total X-ray group and smoker X-ray group than in control and nonsmoker X-ray group, although iron, magnesium, and calcium levels were higher in X-ray group than in control. The copper, zinc, selenium, and aluminum levels were higher in the VCE treatment group than those in X-ray group, although magnesium and calcium levels were decreased by the treatment. The serum zinc, copper, selenium, and magnesium levels were lower in smoker control group when compared to nonsmoker control group. The serum zinc levels were lower in smoker X-ray group than nonsmoker X-ray group, although iron level was higher in smoker X-ray group than in nonsmoker X-ray group. VCE prevents the smoke and X-ray-induced selenium, zinc, magnesium, and copper decrease to strengthen the antioxidant trace element levels in the serum of the technicians.