Browsing by Author "Micic, D. (7006038410)"

Objective: Was to investigate glucose and free fatty acid (FFA) responses to a graded maximal exercise test and recovery period in athletes and sedentary subjects. Subjects and methods: Twelve trained man (TG) and twelve untrained men (UTG) performed an incremental maximal treadmill test. Blood samples were taken from all subjects in the morning before, at the end of the test and after 30 minutes of recovery. Insulin, glucose and FFA levels were determined at these points in time. Results: Glucose concentration did not differ between TG and UTG at rest. Glucose levels increased steadily during exercise in both groups, but this increase was significant only in UTG at the end of the exercise test (+18.71%; P < 0.05) and after 30 min of recovery (+12.05%; P < 0.05) compared to basal levels. FFA concentrations at rest were significantly higher in TG than UTG (P < 0.05). FFA concentration initially significantly decreased during exercise in TG (-50.00%; P < 0.05), and increased during recovery period, but stayed significantly lower than rest values (-25.00%; P < 0.05). In UTG, FFA levels insignificantly decreased (P > 0.05) during exercise and recovery period. Insulin concentration significantly increased during exercise in both groups (+23.89% in TG and +47.64% in UTG, P < 0.05), and stayed significantly higher in recovery period in UTG (+60.82%; P < 0.05). Conclusion: The data presented indicate that chronic physical training markedly influences serum FFA profile in trained group. Our findings also indicate that metabolic response to one bout of maximal-intensity exercise test depends on training status of the subjects and that trained subjects (athletes) could have higher substrate flexibility under high energy demand. © 2015 Elsevier Masson SAS.

Background: Cardiovascular morbidity in adult patients with growth hormone deficiency (GHD) and hypopituitarism is increased. Clustering of cardiovascular risk factors leading to endothelial dysfunction and impaired fibrinolysis has also been reported and may account for progression to overt vascular changes in these patients. However, effect of long lasting GH replacement therapy on fibrinolytic capacity in GH deficient patients has not been investigated so far. Objective: To investigate fibrinolysis before and after challenge with venous occlusion in GHD patients with hypopituitarism before and during one year of growth hormone replacement. Design: Hospital based, interventional, prospective study. Investigated subjects: Twenty one patient with GHD and fourteen healthy control subjects matched for age, sex and body mass index (BMI). Methods: Anthropometric, metabolic and fibrinolytic parameters were measured at the start and after three, six and twelve months of treatment with human recombinant GH. Results: At baseline GHD patients had significantly impaired fibrinolysis compared to healthy persons. During treatment with GH, significant changes were observed in insulin like growth factor 1(IGF-1) [from baseline 6.9(2.4-13.5) to 22.0(9.0-33.0) nmol/l after one month of treatment; p < 0.01] and fibrinolysis. Improvement in fibrinolysis was mostly attributed to improvement of stimulated endothelial tissue plasminogen activator (t-PA) release in response to venous occlusion [from baseline 1.1(0.4-2.6) to 1.9(0.5-8.8) after one year of treatment; p < 0.01]. Conclusion: Growth hormone replacement therapy has favorable effects on t-PA release from endothelium and net fibrinolytic capacity in GHD adults, which may contribute to decrease their risk of vascular complications. © 2013 Elsevier Ltd.

Background: Cardiovascular morbidity in adult patients with growth hormone deficiency (GHD) and hypopituitarism is increased. Clustering of cardiovascular risk factors leading to endothelial dysfunction and impaired fibrinolysis has also been reported and may account for progression to overt vascular changes in these patients. However, effect of long lasting GH replacement therapy on fibrinolytic capacity in GH deficient patients has not been investigated so far. Objective: To investigate fibrinolysis before and after challenge with venous occlusion in GHD patients with hypopituitarism before and during one year of growth hormone replacement. Design: Hospital based, interventional, prospective study. Investigated subjects: Twenty one patient with GHD and fourteen healthy control subjects matched for age, sex and body mass index (BMI). Methods: Anthropometric, metabolic and fibrinolytic parameters were measured at the start and after three, six and twelve months of treatment with human recombinant GH. Results: At baseline GHD patients had significantly impaired fibrinolysis compared to healthy persons. During treatment with GH, significant changes were observed in insulin like growth factor 1(IGF-1) [from baseline 6.9(2.4-13.5) to 22.0(9.0-33.0) nmol/l after one month of treatment; p < 0.01] and fibrinolysis. Improvement in fibrinolysis was mostly attributed to improvement of stimulated endothelial tissue plasminogen activator (t-PA) release in response to venous occlusion [from baseline 1.1(0.4-2.6) to 1.9(0.5-8.8) after one year of treatment; p < 0.01]. Conclusion: Growth hormone replacement therapy has favorable effects on t-PA release from endothelium and net fibrinolytic capacity in GHD adults, which may contribute to decrease their risk of vascular complications. © 2013 Elsevier Ltd.

[No abstract available]

[No abstract available]

Objective: To compare the concentrations of cytokines belonging to Th17 axis (interleukin (IL)-17 and IL-23) and Th1 axis (IL-12 and interferon (IFN)-γ) in obese and lean women, and to investigate their relationships with the proinflammatory adipokine leptin, proinflammatory cytokine macrophage migration inhibitory factor (MIF) and anthropometric and metabolic parameters of obesity. Design: Cross-sectional study. Subjects: Twenty-six obese women (age 20-52 years, body mass index (BMI): 30-48 kg/m2) and 20 healthy lean women (age 23-46 years, BMI: 18-25 kg/m2). Measurements: Plasma levels of cytokines and leptin, BMI, waist circumference (WC) and insulin resistance index HOMA (homeostatic model assessment). Results: Blood concentrations of IL-17, IL-23, MIF and leptin, but not IL-12 or IFN-γ, were higher in obese compared with lean women (P=0.002, 0.046, 0.006 and 0.002, respectively). There was a positive correlation between IL-17 and IL-23 (r s=0.530), which was at the border of statistical significance (P=0.065). Neither IL-17 nor IL-23 correlated with leptin or MIF, and there was no association between IL-17 and IL-23 levels with BMI, WC or HOMA index. Conclusion: Interleukin-23/IL-17 axis is stimulated in obese women independently of the increase in abdominal fat, insulin resistance, leptin and MIF levels. © 2009 Macmillan Publishers Limited All rights reserved.

Objective: To compare the concentrations of cytokines belonging to Th17 axis (interleukin (IL)-17 and IL-23) and Th1 axis (IL-12 and interferon (IFN)-γ) in obese and lean women, and to investigate their relationships with the proinflammatory adipokine leptin, proinflammatory cytokine macrophage migration inhibitory factor (MIF) and anthropometric and metabolic parameters of obesity. Design: Cross-sectional study. Subjects: Twenty-six obese women (age 20-52 years, body mass index (BMI): 30-48 kg/m2) and 20 healthy lean women (age 23-46 years, BMI: 18-25 kg/m2). Measurements: Plasma levels of cytokines and leptin, BMI, waist circumference (WC) and insulin resistance index HOMA (homeostatic model assessment). Results: Blood concentrations of IL-17, IL-23, MIF and leptin, but not IL-12 or IFN-γ, were higher in obese compared with lean women (P=0.002, 0.046, 0.006 and 0.002, respectively). There was a positive correlation between IL-17 and IL-23 (r s=0.530), which was at the border of statistical significance (P=0.065). Neither IL-17 nor IL-23 correlated with leptin or MIF, and there was no association between IL-17 and IL-23 levels with BMI, WC or HOMA index. Conclusion: Interleukin-23/IL-17 axis is stimulated in obese women independently of the increase in abdominal fat, insulin resistance, leptin and MIF levels. © 2009 Macmillan Publishers Limited All rights reserved.

OBJECTIVE: The goal of our study was to determine the rate of neoplasms in patients with other pituitary adenomas (non-functioning and prolactinomas) in comparison with acromegaly which is known to favour the development of neoplasia. DESIGN AND PATIENTS: We reviewed clinical records for 220 patients with acromegaly, 151 patients with non-functioning pituitary adenoma (NF) and 98 patients with prolactinomas. Incidence rates of cancer for patients with pituitary tumours were calculated per person-years of follow-up study. These rates were then compared with sex and age adjusted incidence rates reported by National Tumour Registry. An internal control group of 163 subjects with a nonneoplastic condition, i.e. Graves' disease followed chronically in the same clinic was also studied. The ratios observed to expected were expressed as standardized incidence rates (SIR). The only significant difference between the acromegalic and other pituitary tumours patients was in hypopituitarism, present in 18.2% (acromegaly) 47% (NF) and 18.6% (prolactinomas). RESULTS: Twenty-three malignant tumours were registered in 19 acromegalics (1 Hodgkin disease, 1 myelogenous leukaemia, 1 lymphocytic leukaemia, 3 papillary thyroid carcinomas, 1 ovarian carcinoma, 2 colorectal carcinoma, 1 renal cell carcinoma, 4 cervical carcinoma, 2 skin cancers, 2 pancreatic carcinoma, 4 breast carcinoma, 1 bladder carcinoma). Three acromegalics harboured two malignancies. Patients with acromegaly had a 3.39- fold increased rate of malignant tumours compared with the general population and a 3.21-fold increased rate compared with our internal control group. Eleven malignant tumours were found in patients with NF-pituitary adenomas and 2 in prolactinoma patients (1 lymphoma, 1 multiple myeloma, 1 colonic cancer, 1 renal cell cancer, 1 stomach cancer, 2 lung cancers, 1 cervix carcinoma, 1 breast cancer, 1 testicular carcinoma and 3 melanoma). Patients with NF pituitary adenomas had a 3.91-fold increased rate of malignant tumours compared with the general population and 4.07-fold increase compared with the internal control group. Patients harbouring prolactinomas did not have an increased incidence rate of malignancy compared with the general population or our internal controls. Female patients with acromegaly and male patients with NF-pituitary adenoma had higher incidences of neoplasia. CONCLUSION: We have demonstrated that the overall incidence of malignant tumours in patients with non-functioning pituitary adenomas and acromegaly is significantly higher than expected for general population and for our internal control group.

OBJECTIVE: The goal of our study was to determine the rate of neoplasms in patients with other pituitary adenomas (non-functioning and prolactinomas) in comparison with acromegaly which is known to favour the development of neoplasia. DESIGN AND PATIENTS: We reviewed clinical records for 220 patients with acromegaly, 151 patients with non-functioning pituitary adenoma (NF) and 98 patients with prolactinomas. Incidence rates of cancer for patients with pituitary tumours were calculated per person-years of follow-up study. These rates were then compared with sex and age adjusted incidence rates reported by National Tumour Registry. An internal control group of 163 subjects with a nonneoplastic condition, i.e. Graves' disease followed chronically in the same clinic was also studied. The ratios observed to expected were expressed as standardized incidence rates (SIR). The only significant difference between the acromegalic and other pituitary tumours patients was in hypopituitarism, present in 18.2% (acromegaly) 47% (NF) and 18.6% (prolactinomas). RESULTS: Twenty-three malignant tumours were registered in 19 acromegalics (1 Hodgkin disease, 1 myelogenous leukaemia, 1 lymphocytic leukaemia, 3 papillary thyroid carcinomas, 1 ovarian carcinoma, 2 colorectal carcinoma, 1 renal cell carcinoma, 4 cervical carcinoma, 2 skin cancers, 2 pancreatic carcinoma, 4 breast carcinoma, 1 bladder carcinoma). Three acromegalics harboured two malignancies. Patients with acromegaly had a 3.39- fold increased rate of malignant tumours compared with the general population and a 3.21-fold increased rate compared with our internal control group. Eleven malignant tumours were found in patients with NF-pituitary adenomas and 2 in prolactinoma patients (1 lymphoma, 1 multiple myeloma, 1 colonic cancer, 1 renal cell cancer, 1 stomach cancer, 2 lung cancers, 1 cervix carcinoma, 1 breast cancer, 1 testicular carcinoma and 3 melanoma). Patients with NF pituitary adenomas had a 3.91-fold increased rate of malignant tumours compared with the general population and 4.07-fold increase compared with the internal control group. Patients harbouring prolactinomas did not have an increased incidence rate of malignancy compared with the general population or our internal controls. Female patients with acromegaly and male patients with NF-pituitary adenoma had higher incidences of neoplasia. CONCLUSION: We have demonstrated that the overall incidence of malignant tumours in patients with non-functioning pituitary adenomas and acromegaly is significantly higher than expected for general population and for our internal control group.

This study has shown that there were not any significant increments (during ITT) or decrements (during OGTT) of plasma gastrin values in patients with acromegaly. Neither did gastrin response to ITT or OGTT differ in patients who had hyperprolactinaemia also. There is experimental evidence for increased concentration of gastrin in blood following insulin injection and for reduced concentration in the presence of hyperglycaemia. The release of gastrin depends both on the degree of hypoglycaemia achieved and the adrenergic response provoked as shown by Frier, Cirall, Adrian and Bloom (1982). There is no clear evidence however that these agents are involved in the physiological control of gastrin release (Blair, Grund, Kay, Lund, Reed, Sanders, Thompson and Venables 1978). The fact that gastrin circulates in a number of different molecular forms with different biological potencies further complicates the interpretation.

This study has shown that there were not any significant increments (during ITT) or decrements (during OGTT) of plasma gastrin values in patients with acromegaly. Neither did gastrin response to ITT or OGTT differ in patients who had hyperprolactinaemia also. There is experimental evidence for increased concentration of gastrin in blood following insulin injection and for reduced concentration in the presence of hyperglycaemia. The release of gastrin depends both on the degree of hypoglycaemia achieved and the adrenergic response provoked as shown by Frier, Cirall, Adrian and Bloom (1982). There is no clear evidence however that these agents are involved in the physiological control of gastrin release (Blair, Grund, Kay, Lund, Reed, Sanders, Thompson and Venables 1978). The fact that gastrin circulates in a number of different molecular forms with different biological potencies further complicates the interpretation.

[No abstract available]

[No abstract available]

Context. Cardiovascular risk is increased in women with polycystic ovary syndrome (PCOS). Do insulin sensitizing agents such as metformin (MET) and myoinositol (MI) ameliorate biomarkers of cardiovascular risk? Objective. To compare the effects of MET and MI on blood pressure, lipid profile and high sensitive C-reactive protein (hs-CRP) in women with PCOS in respect to their body mass index (BMI). Design. Open label, parallel randomized, single center study. Subjects and Methods. Sixty six women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of hormones, lipid profile, oxidized LDL (ox-LDL), hs-CRP, blood pressure measurement and clinical assessment of BMI, waist circumference (WC) and Ferriman Gallwey score (FG score) were performed before and after treatment. Results. Thirty patients in each group completed the trial. Compared with MET, MI significantly decreased diastolic blood pressure (DBP) (p=0.036) and significantly increased serum hs-CRP (p=0.043). No differences between groups in total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, ox-LDL and triglycerides were reported after 6 months. Treatment with MI reduced BMI (p=0.037), WC (p=0.005), DBP (p=0.021) and TC (p=0.008). During MET treatment a significant decrease in BMI (p=0.005), WC (p=0.004), FG score (p=0.001), testosterone (p=0.013) and free androgen index (FAI) (p=0.006) was observed. Conclusions. Our study showed an advantage of MI in reduction of DBP and TC thus predicting favorable metabolic and cardiovascular outcomes in PCOS women. MET more effectively decrease indices of hyperandrogenism. © 2021, Acta Endocrinologica Foundation. All rights reserved.

Context. Cardiovascular risk is increased in women with polycystic ovary syndrome (PCOS). Do insulin sensitizing agents such as metformin (MET) and myoinositol (MI) ameliorate biomarkers of cardiovascular risk? Objective. To compare the effects of MET and MI on blood pressure, lipid profile and high sensitive C-reactive protein (hs-CRP) in women with PCOS in respect to their body mass index (BMI). Design. Open label, parallel randomized, single center study. Subjects and Methods. Sixty six women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of hormones, lipid profile, oxidized LDL (ox-LDL), hs-CRP, blood pressure measurement and clinical assessment of BMI, waist circumference (WC) and Ferriman Gallwey score (FG score) were performed before and after treatment. Results. Thirty patients in each group completed the trial. Compared with MET, MI significantly decreased diastolic blood pressure (DBP) (p=0.036) and significantly increased serum hs-CRP (p=0.043). No differences between groups in total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, ox-LDL and triglycerides were reported after 6 months. Treatment with MI reduced BMI (p=0.037), WC (p=0.005), DBP (p=0.021) and TC (p=0.008). During MET treatment a significant decrease in BMI (p=0.005), WC (p=0.004), FG score (p=0.001), testosterone (p=0.013) and free androgen index (FAI) (p=0.006) was observed. Conclusions. Our study showed an advantage of MI in reduction of DBP and TC thus predicting favorable metabolic and cardiovascular outcomes in PCOS women. MET more effectively decrease indices of hyperandrogenism. © 2021, Acta Endocrinologica Foundation. All rights reserved.

Previous studies demonstrated insulin resistance and increased prevalence of impaired glucose tolerance and type 2 diabetes mellitus in patients with primary hyperparathyroidism (PHPT). The effect of curative parathyroidectomy on insulin sensitivity was associated with conflicting results depending on which method for measuring the insulin sensitivity has been used. There was no improvement using HOMA and QUICKI while minimal model demonstrated significant improvement in insulin sensitivity. The aim of our study was to evaluate the insulin sensitivity before and after parathyroidectomy in patients with PHPT using a euglycemic clamp. 44 patients with PHPT and 11 age and body mass index matched healthy controls participated in study protocol. Before surgery M values and HOMA IR suggest insulin resistance in patients with PHPT. There was no difference in M index (3.74±1.89 vs. 4.62±2.27, p>0.05), HOMA IR (2.94±1.39 vs. 3.29±0.81, p>0.05), AUC glucose (863.0±261.3 vs. 842.3±165.5, p>0.05), AUC insulin (7068.7±4159.0 vs. 7229.6±2581.7, p>0.05), ISI (4.73±2.77 vs. 4.25±2.94, p>0.05) and AIR (47.89±32.05 vs. 38.96±21.20, p>0.05) between patients with PHPT and HC. There was significant improvement in insulin sensitivity after parathyroidectomy but both preoperative and postoperative M values were not significantly different in comparison to HC. There were no significant changes in HOMA IR, AUC glucose, AUC insulin, ISI and AIR before and after therapy. In conclusion, we observed significant improvement in insulin sensitivity after parathyroidectomy in patients with PHPT. There was no difference in parameters of insulin secretion before and after parathyroidectomy in patients with PHPT. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart New York.

Previous studies demonstrated insulin resistance and increased prevalence of impaired glucose tolerance and type 2 diabetes mellitus in patients with primary hyperparathyroidism (PHPT). The effect of curative parathyroidectomy on insulin sensitivity was associated with conflicting results depending on which method for measuring the insulin sensitivity has been used. There was no improvement using HOMA and QUICKI while minimal model demonstrated significant improvement in insulin sensitivity. The aim of our study was to evaluate the insulin sensitivity before and after parathyroidectomy in patients with PHPT using a euglycemic clamp. 44 patients with PHPT and 11 age and body mass index matched healthy controls participated in study protocol. Before surgery M values and HOMA IR suggest insulin resistance in patients with PHPT. There was no difference in M index (3.74±1.89 vs. 4.62±2.27, p>0.05), HOMA IR (2.94±1.39 vs. 3.29±0.81, p>0.05), AUC glucose (863.0±261.3 vs. 842.3±165.5, p>0.05), AUC insulin (7068.7±4159.0 vs. 7229.6±2581.7, p>0.05), ISI (4.73±2.77 vs. 4.25±2.94, p>0.05) and AIR (47.89±32.05 vs. 38.96±21.20, p>0.05) between patients with PHPT and HC. There was significant improvement in insulin sensitivity after parathyroidectomy but both preoperative and postoperative M values were not significantly different in comparison to HC. There were no significant changes in HOMA IR, AUC glucose, AUC insulin, ISI and AIR before and after therapy. In conclusion, we observed significant improvement in insulin sensitivity after parathyroidectomy in patients with PHPT. There was no difference in parameters of insulin secretion before and after parathyroidectomy in patients with PHPT. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart New York.

Controversial data were reported concerning fasting ghrelin (decreased, normal or elevated) in polycystic ovary syndrome (PCOS). The aim of our study was to clarify ghrelin levels in non-obese, overweight, and obese PCOS patients; to investigate the effect of acute insulin infusion on ghrelin in PCOS as a chronic insulin-resistant state, with and without the impact of obesity, and to examine ghrelin-androgen interaction. In that order, we evaluated 1) ghrelin levels among 8 non-obese patients with PCOS [body mass index (BMI): 20.52±1.31 kg/m2], 8 overweight and obese patients with PCOS (BMI: 34.36±6.53 kg/m2) and their respective controls, 2) ghrelin suppression during euglycemic hyperinsulinemic clamp, and 3) ghrelin-androgen interrelationship. After overnight fast, 2-h euglycemic hyperinsulinemic clamp, was performed in all investigated women. Fasting ghrelin was significantly lower in non-obese PCOS than in controls (64.74±25.69 vs 108.36±52.60; p<0.05) as well as in overweight and obese PCOS in comparison with controls (38.71±14.18 vs 98.77±40.49; p<0.05). Insulin infusion significantly suppressed ghrelin in all subgroups of investigated women. Analysis of variance for repeatable measures confirmed that there was no significant difference in pattern of response between PCOS and controls. In conclusion, women with PCOS had lower fasting ghrelin and decreased insulin sensitivity independently of their BMI, compared to the controls. In addition, there were no differences between fasting ghrelin levels among non-obese, overweight, and obese women with PCOS. During euglycemic hyperinsulinemic clamp, ghrelin decreased in all studied groups to a similar extent, implying that, compared to chronic hyperinsulinemia, acute hyperinsulinemia reduces ghrelin levels independently of the degree of insulin resistance. ©2007, Editrice Kurtis.

Controversial data were reported concerning fasting ghrelin (decreased, normal or elevated) in polycystic ovary syndrome (PCOS). The aim of our study was to clarify ghrelin levels in non-obese, overweight, and obese PCOS patients; to investigate the effect of acute insulin infusion on ghrelin in PCOS as a chronic insulin-resistant state, with and without the impact of obesity, and to examine ghrelin-androgen interaction. In that order, we evaluated 1) ghrelin levels among 8 non-obese patients with PCOS [body mass index (BMI): 20.52±1.31 kg/m2], 8 overweight and obese patients with PCOS (BMI: 34.36±6.53 kg/m2) and their respective controls, 2) ghrelin suppression during euglycemic hyperinsulinemic clamp, and 3) ghrelin-androgen interrelationship. After overnight fast, 2-h euglycemic hyperinsulinemic clamp, was performed in all investigated women. Fasting ghrelin was significantly lower in non-obese PCOS than in controls (64.74±25.69 vs 108.36±52.60; p<0.05) as well as in overweight and obese PCOS in comparison with controls (38.71±14.18 vs 98.77±40.49; p<0.05). Insulin infusion significantly suppressed ghrelin in all subgroups of investigated women. Analysis of variance for repeatable measures confirmed that there was no significant difference in pattern of response between PCOS and controls. In conclusion, women with PCOS had lower fasting ghrelin and decreased insulin sensitivity independently of their BMI, compared to the controls. In addition, there were no differences between fasting ghrelin levels among non-obese, overweight, and obese women with PCOS. During euglycemic hyperinsulinemic clamp, ghrelin decreased in all studied groups to a similar extent, implying that, compared to chronic hyperinsulinemia, acute hyperinsulinemia reduces ghrelin levels independently of the degree of insulin resistance. ©2007, Editrice Kurtis.