G Kirilov

Medical University of Sofia, Sofia, Oblast Sofiya-Grad, Bulgaria

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Publications (49)59.68 Total impact

  • Article: Macroprolactinemia in patients with prolactinomas: prevalence and clinical significance.
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    ABSTRACT: Data on the prevalence of macroprolactinemia in patients with prolactinomas is quite limited as the presence of high-molecular prolactin forms is suspected mainly in subjects with mild hyperprolactinemia and negative pituitary imaging.The main objective of this observational case-control study was to assess the prevalence and clinical significance of macroprolactinemia among patients with prolactinomas.The study population consisted of 239 subjects: 131 prolactinoma patients and 108 sex-, age- and ethnicity- matched healthy controls. Macroprolactinemia was defined by a PRL recovery after PEG precipitation of<40%.The prevalence of macroprolactinemia among newly diagnosed prolactinoma patients did not differ statistically from the prevalence in the control group (3.5 vs. 3.7%; p=1.000) but was lower although non-significantly than the subgroup of patients treated with dopamine agonists (DA) (3.5 vs.10.8%; p=0.072). Significant association between disruptions of ovarian function and serum levels of the monomeric as well as high-molecular prolactin isoform was found.In few cases, the presence of typical hyperprolactinemia-related clinical symptoms and their disappearance after treatment with DA suggests biological activity of macroprolactin comparable with that of monomeric prolactin isoform. Decrease of macroprolactin levels after DA treatment could suggest tumoral origin of the high-molecular isoform in these rare cases. Although macroprolactinemia is considered a benign condition, pituitary imaging, DA treatment, and prolonged follow-up may be necessary in certain cases. An individualized approach to the management of patients with macroprolactinemia should be applied.
    Experimental and Clinical Endocrinology &amp Diabetes 04/2013; 121(4):201-5. · 1.69 Impact Factor
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    Chapter: Fluorescent Biomarker in Colorectal Cancer
    02/2012; , ISBN: 978-953-51-0062-1
  • Article: Anti-Müllerian hormone in women with polycystic ovary syndrome before and after therapy with metformin.
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    ABSTRACT: Anti-Müllerian hormone (AMH) is largely expressed throughout folliculogenesis and its levels may represent both the quantity and quality of ovarian follicle pool. We conducted this study to evaluate the levels of AMH in women with polycystic ovarian syndrome (PCOS) before and after metformin therapy. 22 consecutive patients with PCOS and 20 healthy age-matched controls were investigated. The patients received 2 550 mg/day metformin for 6 months. Serum levels of AMH, sex hormones, insulin, blood glucose, and lipids were measured before and after metformin therapy. The basal AMH levels in patients with PCOS (42.34±6.42 pmol/l) were significantly elevated in comparison with the controls (21.58±3.41 pmol/l), p=0.008. 17 patients completed 6 months therapy with metformin. Of them, 13 responded clinically by restoration of regular menstrual cycles. The AMH levels of these 13 women decreased from 45.67±9.30 pmol/l to 38.25±6.89 pmol/l (16.27%). In the other 4 patients who did not show satisfactory clinical response to metformin, AMH levels increased from 31.30±16.52 to 80.77±12.73 (p=0.021). The patients who responded to metformin were significantly overweight, had higher BMI, waist circumference, body fat, and blood pressure as compared to nonresponders. AMH levels are significantly elevated in women with PCOS and they may serve as a marker for evaluation of treatment efficacy with metformin. Furthermore, obese PCOS patients are more likely to respond to metformin therapy with maximal doses as compared to the ones with low body mass index.
    Hormone and Metabolic Research 09/2011; 43(10):723-7. · 2.19 Impact Factor
  • Article: Anti-Müllerian hormone and inhibin B levels reflect altered Sertoli cell function in men with metabolic syndrome.
    R Robeva, A Tomova, G Kirilov, P Kumanov
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    ABSTRACT: The aim of the present study was to investigate the Sertoli cell markers inhibin B and anti-Müllerian hormone (AMH) in men with metabolic syndrome (MS). Twenty patients with MS according to the criteria of the International Diabetes Federation and 20 non obese age-matched men were investigated. The levels of testosterone, sex hormone binding globulin (SHBG), gonadotropins, inhibin B and AMH were measured in all of them. In obese patients with MS total testosterone (15.74 ± 6.95 versus 27.84 ± 12.80 nmol l(-1), P = 0.001), SHBG (21.71 ± 11.08 versus 38.80 ± 17.51 nmol l(-1), P = 0.001) and free testosterone (430.35 ± 237.40 versus 613.85 ± 303.65 pmol l(-1), P = 0.040) were significantly lower than in the controls. Interestingly, the inhibin B (103.64 ± 56.77 versus 149.88 ± 68.31 pg ml(-1), P = 0.025) and AMH levels (30.84 ± 13.14 versus 43.14 ± 9.66 pmol l(-1), P = 0.002) were also significantly lower in MS group in comparison to the other participants. The lowest levels of AMH were found in patients with MS and carbohydrate disturbances. The decreased concentrations of testosterone, inhibin B and AMH in patients with MS could reflect an impaired Leydig and Sertoli cell function. Further studies in men with obesity, insulin resistance and diabetes type 2 could reveal more information about the interrelations between the metabolic disturbances and reproductive function in men.
    Andrologia 07/2011; 44 Suppl 1:329-34. · 1.55 Impact Factor
  • Article: Increased plasma endothelin level as an endothelial marker of cardiovascular risk in patients with active acromegaly: a comparison with plasma homocysteine.
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    ABSTRACT: The aim of the present study was to evaluate the plasma endothelin-1 (ET-1) and total homocysteine (tHcy) levels as biochemical markers of endothelial dysfunction and atherosclerosis in patients with active and cured acromegaly in order to assess the relationship between the secretory status of growth hormone (GH)/insulin-like growth factor I (IGF-I) and ET-1/tHcy levels. The patients were divided in two subgroups: 1) patients with active disease (n = 30); and 2) patients with nonactive cured acromegaly (n = 21). Plasma ET-1 levels were directly determined by a highly sensitive enzyme immunoassay and plasma tHcy concentrations were measured by a fluorescence polarization immunoassay. In active acromegaly subjects, plasma ET-1 levels were 1.24 +/- 0.2 pmol/L, significantly higher than in both nonactive acromegalics (0.39 +/- 0.1 pmol/L) and age-matched healthy controls (0.49 +/- 0.2 pmol/L) (P < 0.001). Plasma tHcy concentrations, however, did not differ significantly in all studied groups: nonactive acromegalics: 9.54 +/- 4.42 micromol/L; active acromegalics: 9.0 +/- 3.14 micromol/L; and control subjects: 9.96 +/- 2.95 micromol/L (P > 0.05). In conclusion, our study demonstrated that elevated ET-1 levels probably contributed to premature atherosclerosis and cardiovascular disease and represent a new risk factor for endothelial dysfunction and early vascular complications in acromegaly. We propose that GH and IGF-I secretory status are important determinants of plasma ET-1 but not tHcy levels.
    Methods and Findings in Experimental and Clinical Pharmacology 09/2009; 31(7):457-61. · 0.93 Impact Factor
  • Article: Homocysteine, renin and aldosterone in patients with Cushing's syndrome.
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    ABSTRACT: In the present study, we assessed the levels of fasting homocysteine in patients with active Cushing's syndrome using two different assay methods. To determine a possible link between homocysteine and renin-angiotensin-aldosterone system (RAAS), nine patients with Cushing's syndrome and nine patients with metabolic syndrome were given a 1-month treatment with angiotensin II (AII) receptor blocker valsartan. Plasma homocysteine, active renin and aldosterone did not differ significantly among patients with Cushing's syndrome, patients with metabolic syndrome and controls. As expected, active renin increased significantly during valsartan treatment in patients with Cushing's syndrome as well as in patients with metabolic syndrome. Plasma homocysteine did not change after valsartan treatment, suggesting a lack of direct relationship between homocysteine and RAAS. Our data suggest that homocysteine might not serve as a reliable marker of endogenous hypercortisolism or of cardiovascular risk associated with Cushing's syndrome and metabolic syndrome.
    Methods and Findings in Experimental and Clinical Pharmacology 05/2008; 30(3):221-4. · 0.93 Impact Factor
  • Article: Melatonin-insulin interactions in patients with metabolic syndrome.
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    ABSTRACT: Metabolic syndrome (MS) as a group of risk factors is strongly associated with diabetes type 2 and cardiovascular disease. Insulin resistance plays a key role in the pathogenesis of MS. Recent studies have shown that melatonin may influence insulin secretion and glucose homeostasis. Therefore, the present study analyzed the relationships between the melatonin and the insulin in patients with MS and controls. The melatonin rhythm, insulin and lipid levels were studied in 40 subjects (21 patients and 19 controls) in reproductive age. The night melatonin-insulin ratio was correlated negatively with low-density lipoprotein cholesterol (r = -0.370, p = 0.024) and total cholesterol (r = -0.348, p = 0.030), and positively with high-density lipoprotein cholesterol levels (r = +0.414, p = 0.010). Night-time melatonin levels were related to night-time insulin concentrations (r = +0.313, p = 0.049). The correlation was pronounced in patients with MS (r = +0.640, p = 0.002), but did not reach statistical significance in controls (P > 0.05). In the patients with MS unlike the controls the night-day melatonin difference (%) correlated negatively with the fasting glucose (r = -0.494, p = 0.023) and positively to daily insulin (r = +0.536, p = 0.012). Our results show that melatonin-insulin interactions may exist in patients with MS, as well as relationships between melatonin-insulin ratio and the lipid profile. Pineal disturbances could influence the pathogenesis and the phenotype variations of the MS. Larger studies are needed to confirm or reject this hypothesis and to clarify the role of the melatonin in the metabolic disturbances.
    Journal of Pineal Research 02/2008; 44(1):52-6. · 5.79 Impact Factor
  • Article: Disturbances in gonadal axis in women with anorexia nervosa.
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    ABSTRACT: Anorexia nervosa negatively affects multiple body systems including the reproductive system. To assess the disturbances in the hypothalamic-pituitary-gonadal axis (HPG) and the relationship between the gonadotropins and body weight, duration of the disease and amenorrhea we studied 40 female anorexic patients (aged 14-31 years) with a body mass index (BMI) 15.14+/-1.80 kg/m(2) and a degree of weight loss 28.67+/-8.74%. Fifteen healthy, age-matched women with normal weight served as controls. We investigated the disturbances in the gonadotropin levels before and after stimulation with gonadotropin-releasing hormone (GnRH) 100 microg i.v. One week later 100 mg of clomiphene citrate (CC) was administered orally for 5 days. Basal levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were significantly lower in the patients. The responses of LH to GnRH were diminished, but those of FSH were exaggerated. However, after clomiphene citrate administration, LH increased 5.4 times whereas FSH increased 1.7 times. The basal levels of LH were significantly correlated with body weight (r=+0.373, p<0.05), BMI (r=+0.385, p<0.01) and percentage of the weight loss (r=-0.356, p<0.05). FSH levels were positively correlated with the duration of the disease (r=+0.481, p<0.01) and amenorrhea (r=+0.540, p<0.01). Our study demonstrates dissociation in the secretion of gonadotropins after hypothalamic stimulation in anorexic patients. It also reveals the relationship between alterations in the hormones of the HPG axis, not only with the changes in body weight, but also with the duration of the disease.
    Eating and weight disorders: EWD 01/2008; 12(4):e92-7. · 0.63 Impact Factor
  • Article: Influence of ageing and some lifestyle factors on male gonadal function: a study in Bulgaria.
    P Kumanov, A Tomova, R Robeva, G Kirilov
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    ABSTRACT: There are few systematic studies on the relationship between blood testosterone concentrations and the symptoms of androgen deficiency in ageing males. To assess the changes in sex hormone levels with age in relation with some lifestyle factors, the serum levels of total testosterone (TT), sex-hormone binding globulin (SHBG), luteinising hormone (LH) and follicle stimulating hormone (FSH) were measured in 33 men, age range 40-89 years. In addition, free testosterone (FT) and the free androgen index (FAI) were calculated. Seventeen healthy men under 40 years were involved as controls. The men over 40 years revealed significantly decreased TT, FT and FAI, and in the subgroup of men over 60 years, FSH and SHBG were significantly increased. Pearson's analysis showed that TT levels were significantly correlated with body mass index (BMI) (r = -0.464, P < 0.01) and body weight (r = -0.413, P < 0.05). SHBG levels were significantly correlated not only with age (r = +0.407, P < 0.05), but also with LH (r = +0.605, P < 0.001) and alcohol consumption (r = +0.382, P < 0.05). In conclusion, the TT, FT and FAI decreased in males over 40 years, but the alterations in hormone levels with age are more pronounced in men over 60 years. The important determinants of sex hormones are age, BMI and some lifestyle factors.
    Andrologia 08/2007; 39(4):136-40. · 1.55 Impact Factor
  • Article: Low testosterone levels and unimpaired melatonin secretion in young males with metabolic syndrome.
    R Robeva, G Kirilov, A Tomova, P Kumanov
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    ABSTRACT: The interrelations between testosterone, insulin and melatonin levels in males with metabolic syndrome (MS) are still not clarified, especially in young age groups. The aim of the present study was to compare the testosterone serum levels in young men with MS to those in healthy controls, and to determine the possible changes in their melatonin rhythm, as well as the relation between melatonin, insulin and lipid profile. Fasting insulin and testosterone concentrations were measured in 10 healthy nonobese and 10 MS patients. Blood samples for melatonin, insulin and luteinizing hormone (LH) were collected at 19.00, 03.00 and 11.00 hours. A significant difference was found between the testosterone levels in controls and patients. Luteinizing hormone levels in both groups were similar, however, higher night LH levels in MS patients were observed. No changes in the melatonin concentrations of the two groups were found. In conclusion, total testosterone levels were significantly lower in young men with MS compared with healthy age-matched controls. Mild hypoandrogenia in hyperinsulinaemic patients was not related with changes in their melatonin levels. No alterations in the endogenous melatonin rhythm of the MS patients were found.
    Andrologia 01/2007; 38(6):216-20. · 1.55 Impact Factor
  • Article: Gender-dependent effect of ageing on peripheral insulin action.
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    ABSTRACT: The aim of the present study was to investigate the effect of both gender and age on insulin secretion, peripheral insulin effectiveness and insulin-receptor binding. Eighty healthy volunteers, 40 females of mean age 38.47 +/- 11.37 years and mean BMI 21.99 +/- 2.06 kg/m(2) and 40 males of mean age 34.87 +/- 11.22 years and mean BMI 22.65 +/- 2.31 kg/m(2), with normal glucose tolerance participated in the study. Peripheral insulin effectiveness was measured by the artificial endocrine pancreas, using the euglycaemic hyperinsulinaemic clamp technique and insulin-receptor binding on circulating mononuclear blood cells. Peripheral insulin sensitivity was significantly higher in females as compared to males (p < 0.001), while males demonstrated higher total number of insulin receptors (p < 0.0001) and number of high-affinity receptors (p < 0.01). Peripheral insulin sensitivity decreased with ageing in both males and females, the reduction in females being more pronounced (p < 0.05). In the group under 40 years, the females demonstrated significantly higher insulin sensitivity as compared to males (p < 0.001) and lower insulin-receptor binding. Over 40 years, females presented higher peripheral insulin sensitivity and higher insulin-receptor binding. The percentage of specifically bound insulin increased significantly with ageing in females and decreased in males. We consider that probably the higher androgen level in males affects the post-receptor processes in insulin action and despite the higher insulin-receptor binding, males have lower insulin sensitivity. The androgen levels in females increase with ageing, which could probably affect peripheral insulin sensitivity at the post-receptor level. In conclusion, our results demonstrate that when analysing peripheral insulin effectiveness and insulin-receptor binding, one should always consider both gender and age.
    International Journal of Clinical Practice 05/2005; 59(4):422-6. · 2.41 Impact Factor
  • Article: Markers of vascular function in hypertension due to Cushing's syndrome.
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    ABSTRACT: There are limited data regarding the role of vascular endothelial growth factor (VEGF) in arterial hypertension. The aim of the study was to determine some markers of vascular function, including VEGF, active renin and prostaglandin E (2) (PGE (2)) in patients with endocrine hypertension resulting from Cushing's syndrome. The study comprised 32 patients with active Cushing's syndrome, 22 patients with essential hypertension, and 24 healthy volunteers. VEGF was significantly elevated in the groups of patients compared to controls. VEGF levels in the patients with Cushing's syndrome were significantly higher than in patients with essential hypertension. We did not find significant differences in VEGF levels between patients with Cushing's disease and Cushing's syndrome due to adrenal tumor. Active renin and PGE (2) levels did not differ significantly among groups. VEGF levels were significantly elevated in endocrine hypertension due to glucocorticoid excess. Higher VEGF levels were detected in patients with Cushing's syndrome compared to patients with essential hypertension. Based on our results, we could not judge the extent to which this VEGF elevation in the patients with Cushing's syndrome was due to the hypertension itself and/or to the presence of adrenal tumor/hyperplasia.
    Hormone and Metabolic Research 02/2005; 37(1):36-9. · 2.19 Impact Factor
  • Article: Sibutramine in the treatment of obesity in type 2 diabetic patients and in nondiabetic subjects.
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    ABSTRACT: Obesity is considered a chronic disease requiring treatment. The effect of sibutramine combined with hypocaloric diet and exercise on body weight, body fat mass, lipids, glycemic control, insulin secretion and insulin resistance was evaluated in a randomized, controlled, open-label study. A total of 44 obese type 2 diabetic patients (aged 45.2+/-5.2 years, BMI 33.62+/-2.2 kg/m(2)) and 49 obese nondiabetic subjects (aged 41.9+/-5.7 years, BMI 34.3+/-2.6 kg/m(2)) were treated with sibutramine for 3 months. Moreover, 39 age-matched obese type 2 diabetic patients and 41 obese nondiabetic subjects only on hypocaloric diet and exercise served as control groups. Insulin secretion was estimated during intravenous glucose tolerance test; insulin resistance was assessed by the HOMA index. There was a significant reduction in body weight in both sibutramine-treated diabetic patients (7.1%) and nondiabetic subjects (9.1%), accompanied by a significant reduction in body fat mass. HbA1c decreased significantly in the diabetic patients after sibutramine treatment. There was a significant improvement of lipid parameters in the two groups. Insulin resistance decreased by 21.9% in the sibutramine-treated diabetic patients and by 38.5% in the nondiabetic group. Weight loss was accompanied by an increase of 43.8% in first phase insulin secretion in the sibutramine-treated diabetic group; in the treated nondiabetic subjects there was a decrease in first and second phase insulin secretion and the area under the curve for total insulin secretion. In conclusion, sibutramine leads to a significant reduction in body weight, body fat mass and waist and hip circumferences; it improves insulin sensitivity, insulin secretion, glycaemic control and lipid parameters in both diabetic and nondiabetic obese subjects.
    Acta Diabetologica 01/2005; 41(4):146-53. · 2.78 Impact Factor
  • Article: Vascular endothelial growth factor (VEGF), prostaglandin E2(PGE2) and active renin in hypertension of adrenal origin.
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    ABSTRACT: There are limited data regarding the role of vascular endothelial growth factor (VEGF) in arterial hypertension. The aim of the present study was to determine some markers of vascular function, including VEGF, active renin and prostaglandin E2 (PGE2) in patients with endocrine hypertension. The study comprised: 30 patients with primary aldosteronism; 32 patients with active Cushing's syndrome; 19 patients with pheochromocytoma; 22 patients with essential hypertension and 24 healthy volunteers. VEGF was significantly elevated in all groups of patients as compared to the controls. VEGF levels in patients with Cushing's syndrome were significantly higher than those in patients with essential hypertension and primary aldosteronism. We did not find significant differences in VEGF levels between patients with Conn adenomas and idiopathic aldosteronism as well as between patients with Cushing's disease and Cushing's syndrome. PGE2 levels were not significantly different among the groups. Active renin was significantly the lowest in patients with primary aldosteronism and significantly the highest in those with pheochromocytoma compared to controls. The level of active renin in patients with primary aldosteronism was significantly lower than in patients with Cushing's syndrome and pheochromocytoma. In conclusion, VEGF levels were significantly elevated in patients with endocrine hypertension due to glucocorticoid, mineralocorticoid and/or catecholamine excess. The highest VEGF levels were detected in patients with Cushing's syndrome. The latter is associated with accelerated development of atherosclerosis and increased cardiovascular risk. VEGF might contribute to the cardiovascular risk in this disease. This effect was not likely to be PGE2 mediated.
    Journal of endocrinological investigation 10/2004; 27(8):742-6. · 1.57 Impact Factor
  • Article: The effect of smoking on peripheral insulin sensitivity and plasma endothelin level.
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    ABSTRACT: The aim of the present study was to investigate the effect of smoking on peripheral insulin effectiveness. Seven healthy volunteers, nonsmokers, of mean age 39.6 +/- 7.1 Years and mean BMI 22.65 +/- 11.98 kg/m2, without family history of diabetes mellitus, with normal blood pressure participated in the study. All the parameters were studied twice - at baseline as well as after smoking (4 cigarettes per one hour). The study was performed in three days: at the first day we studied peripheral insulin effectiveness (M) in vivo by the artificial endocrine pancreas (Biostator), using the euglycaemic hyperinsulinaemic clamp technique, and insulin-receptor binding on circulating mononuclear blood cells; at the second day - the same parameters after one-hour smoking during the third hour of clamping; at the third day - plasma endothelin level, blood pressure and heart rate at baseline and after one-hour smoking. There was a significant decrease in glucose utilization during the second clamp test, when the volunteers smoked during the third hour as compared to the test at baseline (p=0.04). This was accompanied by a significant decrease in insulin receptor affinity (p=0.04). Systolic blood pressure and heart rate increased significantly after one-hour smoking (p=0.03 and p=0.001, respectively). Plasma endothelin level increased significantly after smoking (from 0.62 +/- 0.15 pg/ml to 2.05 +/- 1.67 pg/ml, p=0.03). Our results demonstrate that smoking decreases peripheral insulin sensitivity reducing insulin receptor affinity. We have confirmed that smoking increases plasma endothelin level, which probably by causing vasoconstriction and consequent tIssue hypoxaemia could decrease peripheral glucose utilization. We consider that smoking could also have a direct effect on insulin receptor affinity, thus leading to decreased peripheral insulin effectiveness.
    Diabetes & Metabolism 05/2004; 30(2):147-52. · 2.41 Impact Factor
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    Article: Elevated plasma endothelin as an additional cardiovascular risk factor in patients with Cushing's syndrome.
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    ABSTRACT: Recently the pathophysiological role of endothelin (ET) has been presumed in a number of adrenal disorders such as primary hyperaldosteronism, pheochromocytoma and adrenocortical insufficiency. The aim of the present study was to evaluate circulating ET-1 levels in patients with endogenous Cushing's syndrome. Plasma ET-1 levels were determined by highly sensitive RIA. Thirteen untreated subjects with Cushing's syndrome were studied: eight women and five men of mean age 44.2+/-9.5 Years (s.d.). In ten of them, Cushing's disease had been diagnosed and three had adrenal adenomas. ET-1 was 3-fold higher in the patient group than in age-matched healthy controls (n=13): 1.59+/-0.78 vs 0.46+/-0.20 pmol/l respectively, P<0.001. In adrenal adenoma patients, ET-1 was not significantly higher than in the Cushing's disease subjects (1.84+/-0.67 vs 1.51+/-0.83 pmol/l respectively, P>0.05). In three patients who died of severe cardiovascular complications, plasma ET-1 was significantly higher than in the remaining patients (2.34+/-0.35 pmol/l, P<0.05). A positive correlation was found between the total cholesterol (6.94+/-1.75 mmol/l) and ET-1 levels in the patients with Cushing's syndrome: r=+0.73, P<0.02. No correlation was observed, however, between the levels of ET-1 and blood pressure (183+/-37/106+/-18 mmHg), plasma cortisol levels (455.2+/-74.5 nmol/l) or urinary cortisol excretion (1463+/-726 nmol/24 h). The successful treatment and correction of hypercortisolism in seven patients led to insignificant reduction in plasma ET from 1.34+/-0.69 to 0.73+/-0.53 pmol/l, P>0.05. Our results clearly demonstrate that the ET system is activated in Cushing's syndrome. Elevated plasma ET-1 levels probably play a role in the pathogenesis of accelerated and early atherosclerosis development in this disorder.
    European Journal of Endocrinology 12/2003; 149(6):549-53. · 3.42 Impact Factor
  • Article: L-carnitine consecutively administered to patients on hemodialysis improves beta-cell response.
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    ABSTRACT: Eight patients with end stage renal disease (ESRD) on chronic hemodialysis (CHD) treatment were supplemented with 1 g L-carnitine intravenously (i.v.) after each dialysis session for one month. A Tolbutamide test was done and blood sugar (BS), serum C-peptide (CP) were measured at 0, 20 and 60 minutes, as well as the plasma L-carnitine level before and after treatment. Delta CP and the area under CP curve were ascertained. After L-carnitine application delta CP was significantly increased (1.33 +/- 0.63 vs. 2.24 +/- 1.0 nmol/L; p<0.05) and also the area of the stimulated secretion under the CP curve (14.93 +/- 11.11 vs. 36.88 +/- 25.36 nmol/L x 60 min.; p<0.05). The fasting BS-level was significantly lower after the treatment--3.85 +/- 0.43 vs. 4.76 +/- 1.02 mmol/L; p<0.05 and plasma L-carnitine level significantly increased (72.8 +/- 43.2 vs. 35.2 +/- 18.3 mcmol/L; p<0.05) Improving the oxidative processes in peripheral tissues, L-carnitine increases the peripheral effectiveness of insulin and relieves the overstretched beta-cell apparatus.
    The International journal of artificial organs 05/2003; 26(4):304-7. · 1.86 Impact Factor
  • Article: The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients.
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    ABSTRACT: The aim of this study was to evaluate the effect of vitamin D3 supplementation on insulin secretion and insulin resistance. Ten females with type 2 diabetes being treated with oral hypoglycaemic agents and with normal serum and urine calcium levels were enrolled in the study. The study was conducted in March, when levels of vitamin D are lowest in our region. The level of plasma 25(OH)D was measured (normal range in winter 25-120 nmol/l). The first (FPIS) and second (SPIS) phases of insulin secretion were studied during IVGTT. Peripheral insulin resistance was measured. A group of 17 age- and BMI-matched females with normal glucose tolerance served as a control group. The diabetic patients were treated with cholecalciferol 1332 IU daily for one month. The mean plasma 25(OH)D level was 35.3 +/- 15.1 nmol/l at baseline, 70% of patients being vitamin D deficient. After one month of treatment with vitamin D3, the plasma 25(OH)D level increased by a mean of 75.8%; 70% of the patients achieved normal vitamin D levels. FPIS increased significantly by 34.3%, while the change in SPIS of 20.4% was not significant (p > 0.8). We found a significant correlation between the change in FPIS and the change in 25(OH)D level after vitamin D3 supplementation (p < 0.018). The results showed a decrease of 21.4% in insulin resistance after one month, but the change was not significant. Bearing in mind that the main defects in type 2 diabetes mellitus are reduced FPIS and insulin resistance, and the favourable effect vitamin D3 had on them, we suggest vitamin D3 deficiency may at least partly contribute to the impairment of insulin secretion and probably of insulin action. Our results suggest that vitamin D3 supplementation could be an element in the complex treatment of type 2 diabetes mellitus during the winter.
    International Journal of Clinical Practice 05/2003; 57(4):258-61. · 2.41 Impact Factor
  • Article: Intravenous glucose tolerance test and anti‐GAD65 antibodies in the diagnosis of the type of diabetes mellitus
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    ABSTRACT: The aim of the present study was to evaluate the importance of the phases of insulin secretion, measured during an intravenous glucose tolerance test (IVGTT), and anti-GAD65 antibodies as a beta-cell autoimmune marker, in the proper early diagnosis of the type of diabetes in normal-weight patients aged 30–45 years. Forty-two newly diagnosed diabetic patients (25 males and 17 females), of mean age 37.2±6.9 years and BMI 24.4±2.7kg/m2, were enrolled in the study; 19 subjects with normal glucose tolerance, of mean age 36.8±7.4 years and mean BMI 24.3±2.3 kg/m2, served as a control group. Using the data from IVGTT and anti-GAD65 antibodies, the diabetic patients were divided into two groups—type 1 diabetic patients (n=19), showing loss of first (FPIS) and second (SPIS) phases of insulin secretion: 12.9±5.1mU/L versus 134.4±43.7mU/L in the control group, p < 0.001; and 15.4±6.4mU/L versus 64.4±23.6mU/L in the control group, p<0.001, respectively, as well as high prevalence of anti-GAD65 antibodies: 73.7%; and type 2 diabetic patients (n=23), who demonstrated declined FPIS: 25.9±11.5mU/L (p<0.001 compared with the healthy controls and p<0.01 compared with type 1 diabetic patients), and relatively preserved but retarded SPIS (61.1±17.7mU/L, p>0.1 compared with the healthy controls), none of them being anti-GAD65 positive. Our results demonstrate that IVGTT allows precise assessment of the phases of insulin secretion and helps to set proper early diagnosis of the type of diabetes. The presence of anti-GAD65 antibodies alone can set the diagnosis type 1 diabetes, while anti-GAD65 negativity requires the performance of IVGTT, which can then distinguish between anti-GAD65 negative type 1 diabetic patients and type 2 diabetic patients. The combination of IVGTT and anti-GAD65 antibodies appears to be of clinical importance in distinguishing between type 1 and type 2 diabetes mellitus in normal weight newly diagnosed patients aged 30–45 years and in prescribing adequate treatment. Copyright © 2003 John Wiley & Sons, Ltd.
    Practical Diabetes International 03/2003; 20(1):13 - 17.
  • Article: [Cyproterone acetate improves beta-cell function in postmenopausal women with diabetes mellitus type 2].
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    ABSTRACT: Menopause is associated with two main risk factors for the development of type 2 diabetes mellitus--impaired beta-cell insulin secretion and insulin resistance. Physiologically estrogens improve carbohydrate metabolism, but this is not the case with different progestogens. The aim of the present study was to evaluate the effect of Cyproterone acetate (a progestogen with antiandrogenic activity) on insulin secretion, peripheral insulin sensitivity, lipid parameters and parameters of oxidative stress. Seven type 2 diabetic females, of mean age 55.4 +/- 4.7 years and mean BMI 30.8 +/- 9.39 kg/m2, in menopause for average 5 years, in good borderline glycaemic control (mean HbAic 7.8%), with dyslipidaemia, normal parameters of calcium and phosphate metabolism and with osteopenia (T-score < 88%) were enrolled in the study. They were treated with Estradiol valerate + Cyproterone acetate (Climen, Schering) for three months. Phases of insulin secretion--first phase (FPIS), second phase (SPIS) and AUC for FPIS and SPIS were assessed during IVGTT. Insulin sensitivity was determined with the manual method of euglycaemic hyperinsulinaemic clamp technique. The postmenopausal diabetic women in the present study were with overweight and obesity; they did not increase their body weight during HRT and even decreased it by mean 0.7%. Insulin secretion improved after Climen--FPIS increased by 16% and SPIS by 44%. Insulin sensitivity increased by 15%; triglycerides decreased by 16% and HDL-cholesterol increased by 27%. Total antioxidant capacity of the serum (TAOK) increased by 7%. The favourable effect on the pathophysiological mechanisms improved metabolic control--HbAic was reduced by mean 3% after 3 months. In conclusion, our results suggest that HRT with the progestogen Cyproterone acetate (Climen) should be preferred in postmenopausal type 2 diabetic females with predominant beta-cell insulin secretion defect.
    Akusherstvo i ginekologiia 01/2003; 42(5):8-14.