[Show abstract][Hide abstract] ABSTRACT: Metabolic disorders and cardiovascular events are increased in hypogonadism. Serum HDL composition is a better cardiovascular predictor than the HDL counts. However, there is no information about the HDL subfractions in patients with hypogonadism. We designed a prospective study to investigate the HDL subfractions in treatment naïve subjects with hypogonadism and the effects of 2 different testosterone replacement regimens on the HDL subfractions. Seventy young male patients with congenital hypogonadotropic hypogonadism (CHH) and 70 age and BMI-matched healthy males were enrolled in the present study. The patients were assigned to receive intramuscular injections of testosterone esters 250 mg every 3 weeks and transdermal testosterone applications 50 mg daily. Biochemical investigations including HDL subfractions and insulin resistance were done. Patients with CHH had higher levels of insulin, HOMA-IR, WC, triglyceride, and diastolic blood pressure. Although, the HDL cholesterol concentrations were similar in both groups, hypogonadal patients had lower HDL2 and higher HDL3 levels. The total testosterone levels were independent determinants of the HDL2 subfractions. During the follow-up, a significant increase in the BMI and WC values and a significant decrease in the levels of total cholesterol, HDL cholesterol, and HDL3 were observed. No difference was present between the 2 treatment arms. These results show that patients with hypogonadism have unfavorable HDL compositions in addition to the other dysmetabolic features. However, testosterone replacement for about six months neither improves the metabolic problems nor the HDL composition. Mechanistic studies are warranted to better understand the cardiovascular effects of unfavorable HDL compositions in hypogonadism.
Hormone and Metabolic Research 04/2013; 45(6). DOI:10.1055/s-0033-1343447 · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low grade inflammation has been reported to participate in the pathogenesis of insulin resistance. Chitotriosidase (ChT), a protein secreted by activated macrophages, has been shown to be involved in chronic inflammatory responses. In the present study, serum chitotriosidase activity and its relationship with insulin resistance were determined in patients with PCOS.34 patients with PCOS and 44 age and body mass index (BMI) matched healthy controls were enrolled in the study. ChT activity was measured by the fluorescence method. High sensitivity C reactive protein (hs-CRP) and adiponectin levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula.Plasma ChT activity, hs-CRP level and HOMA-IR score were significantly higher (p=0.024, p=0.002, p=0.001, respectively) while plasma adiponectin concentration was significantly lower (p=0.018) in women with PCOS compared to healthy controls. Blood ChT activity correlated positively with age, waist-to-hip ratio (WHR), BMI, hs-CRP, HOMA-IR and negatively with blood adiponectin level. After adjustment for age and BMI, ChT activity, total testosterone level and WHR remained as the independent predictors of HOMA-IR score in logistic regression analysis.ChT activity is increased in patients with PCOS in concordance with insulin resistance. These findings may reflect the pronounced risk for metabolic syndrome and atherosclerotic diseases in this particular patient group.
[Show abstract][Hide abstract] ABSTRACT: The amount of epicardial adipose tissue (EAT), a component of body visceral adiposity, has been linked to the presence and severity of cardiovascular disease through multiple mechanisms. Polycystic ovary syndrome (PCOS) is characterized by insulin resistance and subclinical inflammation, which participate in the mechanism of atherosclerosis. We searched if the patients with PCOS have increased EAT thickness (EATT), along with its relation to the measures of adiposity and insulin sensitivity. A total of 41 subjects with PCOS and 46 age and body mass index (BMI) matched healthy controls were enrolled. EAT was measured by echocardiography above the free wall of the right ventricle. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) formula, and plasma adiponectin level was measured by ELISA. Compared to healthy controls EATT and HOMA-IR score were significantly higher (p=0.0001 for both) while plasma adiponectin concentration was significantly lower (p=0.048) in women with PCOS. EATT correlated positively with total cholesterol, triglyceride, luteinizing hormone (LH) and negatively with sex hormon binding globuline (p<0.05 for all), whereas it displayed no correlation to plasma adiponectin level (p=0.924). Triglyceride level was the significant determinant of EATT in logistic regression analysis (p=0.035). Thickness of the EAT is increased in patients with PCOS in conjunction with hyperandrogenity. Prospective studies are required to identify the relation of EAT and cardiovascular risk in patients with PCOS.
[Show abstract][Hide abstract] ABSTRACT: Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low-grade inflammation has been anticipated to play role in the pathogenesis of both insulin resistance and atherosclerosis. Pentraxin 3 (PTX3) is an inflammatory mediator synthesized in a variety of cells and tissues including heart, vascular endothelial cells, macrophages and adipocytes. In the present study, serum PTX3 level and its relationship with insulin resistance were investigated in patients with PCOS.
Forty patients with PCOS and 40 age- and body mass index (BMI)-matched healthy controls were enrolled in the study. PTX3 and high-sensitivity C-reactive protein (hs-CRP) levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula.
Plasma levels of PTX3, hs-CRP and HOMA-IR scores were all significantly higher (p = 0.021, p = 0.002 and p = 0.0001, respectively) in women with PCOS compared with healthy controls. Blood PTX3 level correlated positively with hs-CRP, BMI, waist-to-hip ratio (WHR), HOMA-IR and negatively with high-density lipoprotein cholesterol level (p < 0.05, for all). After adjustment for age and BMI, PTX3, total testosterone levels and BMI remained as independent predictors of HOMA-IR scores (p < 0.05, for all).
PTX3 level is increased in patients with PCOS in concordance with insulin resistance.
[Show abstract][Hide abstract] ABSTRACT: The relationship between metabolic syndrome (MS) and hypogonadism has always been investigated in study groups confounded with aging, obesity or chronic metabolic disorders. So far, there has been no data about the presence of MS in young hypogonadal patients. Also, there is controversial data about the metabolic effects of testosterone replacement therapy. We investigated the frequency of MS in treatment-naïve, young men with congenital hypogonadal hypogonadism (CHH). We also searched for the effect of testosterone replacement on the metabolic profiles of this specific patient group.
A total of 332 patients (age 21.68 ± 2.09 years) were enrolled. The control group included 395 age- and body mass index (BMI)-matched healthy young men (age 21.39 ± 1.49 years). Standard regimen of testosterone esters (250 mg/3 weeks) was given to 208 patients.
MS was more prevalent in CHH (P<0.001) according to healthy controls. The patients had higher arterial blood pressure, waist circumference (WC), triglyceride (P<0.001 for all), fasting glucose (P=0.02), fasting insulin (P=0.004), homeostatic model assessment of insulin resistance (HOMA-IR) (P=0.002) and lower high density lipoprotein (HDL) cholesterol (P<0.001) levels. After 5.63±2.6 months of testosterone treatment, the BMI, WC (P<0.001 for both), systolic blood pressure (P=0.002) and triglyceride level (P=0.04) were increased and the total and HDL cholesterol levels were decreased (P=0.02 and P<0.001 respectively).
This study shows increased prevalence of MS and unfavorable effects of testosterone replacement in young patients with CHH. Long-term follow-up studies are warranted to investigate the cardiovascular safety of testosterone treatment in this specific population.
European Journal of Endocrinology 02/2011; 164(5):759-64. DOI:10.1530/EJE-10-0951 · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mechanism of testosterone therapy on insulin sensitivity is unclear. The aim of the present study was to determine effects of androgen therapy on glucose metabolism, body composition, and adipocytokines in patients with idiopathic hypogonadotrophic hypogonadism (IHH). One hundred two male subjects with IHH were enrolled in the study. Body fat and fat-free mass were determined by bioelectrical impedance analysis (BIA), fasting plasma leptin, resistin levels were measured by using ELISA kits commercially available and antropometric measurements were obtained before and after six months of androgen replacement therapy. Insulin sensitivity was calculated by HOMA-IR and QUICKI formulas. Following six months of androgen replacement therapy, statistically significant reductions were seen in body fat mass (27.41 ± 6.32% vs. 12.23 ± 3.74%, p= 0.001), HOMA-IR (5.61 ± 1.98 vs. 2.13 ± 0.72, p= 0.001), plasma leptin (15.32 ± 4.21 vs. 5.63 ± 1.34 ng/mL, p= 0.001) and resistin (6.48 ± 1.52 vs. 2.91 ± 1.94 ng/mL, p= 0.001) levels. Plasma free testosterone levels (2.64 ± 1.32 vs. 22.74 ± 2.52 pg/mL, p= 0.001), body fat-free mass (72.92 ± 6.73 % vs. 89.64 ± 4.18 %, p= 0.001), body mass index (21.71 ± 2.2 vs. 22.41 ± 1.89 kg/m(2), p= 0.001) and QUICKI index (0.31 ± 0.02 vs. 0.35 ± 0.01, p= 0.001) significantly increased after androgen replacement therapy. It was demonstrated that testosterone therapy may not only treat hypogonadism, but also have ameliorating effects on insulin sensitivity. Reduction in leptin and resistin concentrations may contribute to this phenomenon.
[Show abstract][Hide abstract] ABSTRACT: Home glucose meters (HGMs) may not be accurate enough to sense hypoglycemia. We evaluated the accuracy and the capillary and venous comparability of five different HGMs (Optium Xceed [Abbott Diabetes Care, Alameda, CA, USA], Contour TS [Bayer Diabetes Care, Basel, Switzerland], Accu-Chek Go [Roche Ltd., Basel, Switzerland], OneTouch Select [Lifescan, Milpitas, CA, USA], and EZ Smart [Tyson Bioresearch Inc., Chu-Nan, Taiwan]) in an adult population.
The insulin hypoglycemia test was performed to 59 subjects (56 males; 23.6 +/- 3.2 years old). Glucose was measured from forearm venous blood and finger capillary samples both before and after regular insulin (0.1 U/kg) was injected. Venous samples were analyzed in the reference laboratory by the hexokinase method. In vitro tests for method comparison and precision analyses were also performed by spiking the glucose-depleted venous blood.
All HGMs failed to sense hypoglycemia to some extend. EZ Smart was significantly inferior in critical error Zone D, and OneTouch Select was significantly inferior in the clinically unimportant error Zone B. Accu-Chek Go, Optium Xceed, and Contour TS had similar performances and were significantly better than the other two HGMs according to error grid analysis or International Organization for Standardization criteria. The in vitro tests were consistent with the above clinical data. The capillary and venous consistencies of Accu-Chek Go and OneTouch Select were better than the other HGMs.
The present results show that not all the HGMs are accurate enough in low blood glucose levels. The patients and the caregivers should be aware of these restrictions of the HGMs and give more credit to the symptoms of hypoglycemia than the values obtained by the HGMs. Finally, these results indicate that there is a need for the revision of the accuracy standards of HGMs in low blood glucose levels.
[Show abstract][Hide abstract] ABSTRACT: Both apelin and asymetric dymethyl arginine (ADMA) regulate blood pressures. Low apelin and high ADMA levels have been reported in several cardiometabolic disorders. However, there is no data about ADMA and apelin levels in essential hypertension and any relationship between them. We investigated a group of newly diagnosed and untreated 30 young hypertensive men and 30 healthy controls. Apelin levels were significantly lower and the ADMA levels were significantly higher in the patients (p = 0.04 for both). Both ADMA and apelin were related to the systolic blood pressures (SBP) (beta = -0.393, p = 0.003; beta = 0.285, p = 0.03, respectively). Future studies are necessary in order to clearly define the role of ADMA and apelin in the pathogenesis of essential hypertension.
[Show abstract][Hide abstract] ABSTRACT: The objective of the present study was to evaluate the role of visfatin in gestational diabetes mellitus.
Forty-five pregnant women at 24 to 28 weeks' gestation were assigned to consume an initial screening test using a 1-h 50-g glucose load, and then a 3-h 100-g glucose load. The study group consisted of 23 patients who were diagnosed with gestational diabetes mellitus and the control group consisted of 22 healthy pregnant women. We studied the levels of visfatin and the other parameters of inflammation, glucose and lipid metabolism between the 24th and 28th week of gestation and also between the 6th and 10th week after delivery.
Plasma visfatin and glucose levels at 60 min after a 50-g and a 100-g glucose load between the 24th and 28th week of gestation were significantly higher in the gestational diabetes group than in the control group. There were no statistical differences in visfatin levels between the groups at 6-10 weeks post-partum.
Visfatin levels were significantly elevated in women with gestational diabetes mellitus and during the course of pregnancy and increased visfatin concentrations were reduced within 6 to 10 weeks after delivery.
[Show abstract][Hide abstract] ABSTRACT: Diabetes mellitus (DM) is a complex disease that affects many systems. The most important cells of the immune system are lymphomononuclear (LMN) cells. Here, we aimed to evaluate the energy metabolism of LMN cells in patients with diabetes and impaired glucose tolerance. We measured LMN cell energy metabolism in patients with type 2 diabetes mellitus, impaired glucose tolerance (IGT) and healthy subjects. Cells were freshly isolated from peripheral blood and the subgroups were determined by flow cytometric method. Lactate production and glycogen utilization were significantly increased in the LMN cells of patients with type 2 DM and IGT when compared with healthy volunteers. No statistical difference was observed between the patients with type 2 DM and IGT. There was a significant correlation between fasting plasma glucose and lactate production in LMN cells. LMN cells changed their energy pathway in a diabetic state and preferred anaerobic glycolysis. Prediabetic range also affected energy metabolism in LMN cells. This abnormal energy production might cause dysfunction in LMN cells and the immune system in diabetic and prediabetic patients. In conclusion, we concluded that impaired glucose metabolism could change energy metabolism.
[Show abstract][Hide abstract] ABSTRACT: Hemoglobin (Hb) regulates the endothelial function by modulating the bio-availability of NO at the tissue level. A significant direct relationship is present between the Hb levels and endothelial functions in patients with Type 2 diabetes. Testing whether this association also exists in subjects with prediabetes is important because prediabetes is associated with an increased risk of cardiovascular disease and mortality. Therefore, we investigated the association of Hb both with the classical cardiac risk factors and the markers for endothelial dysfunction and inflammation, in subjects with impaired glucose tolerance (IGT).
We enrolled 69 normotensive, and cardiovascular events free subjects with IGT (M=40, age=45.50+/-6.8 yr). Plasma insulin, hsCRP, soluble CD40L, vonWillebrand factor, p-selectin levels were measured. The parameters given according to the higher and lower median Hb values of the subjects were compared.
Subjects with the higher Hb levels exhibited lower HDL-C (46.68+/-10.8 mg/dl vs 51.5+/-8.9 mg/dl; P=0.04) and higher systolic (122.57+/-6.2 mmHg vs 116.17+/-7.4 mmHg; p < 0.001) and diastolic (79.14+/-3.73 mmHg vs 75.58+/-6.1 mmHg; P=0.005) blood pressures and sCD40L (7.9+/-3.8 ng/ml vs 6.07+/-2.1 ng/ml; P=0.02) levels. Hb levels were correlated to the HDL cholesterol, sCD40L, systolic and diastolic blood pressures and waist circumference (r=-0.28, P=0.02; r=0.29, P=0.02; r=0.53, P < 0.001; r=0.41, P=0.001; r=0.42, P < 0.001 respectively). According to the multiple logistic regression analysis, Hb was the determinant of sCD40L levels (beta=0.437, P < 0.001).
These results indicate that there may be a link with higher Hb values and cardiovascular risk factors in patients with IGT. Further investigation is warranted to understand the clinical implications of these findings in subjects with prediabetes.
Clinical and investigative medicine. Medecine clinique et experimentale 12/2009; 32(6):E244. · 1.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemoglobin (Hb) is the main carrier and buffer of nitric oxide. Evidence has been produced that Hb concentration is inversely related with endothelial function in human diseases. Testing whether this association exists also in diabetic patients stage 1 to 2 chronic kidney disease (CKD) is important because anemia in these patients starts at an earlier stage than in other renal diseases. The relationship was investigated between Hb and flow-mediated dilation (FMD) levels of the patients with diabetic nephropathy in a cross-sectional design.
Eighty-nine diabetics with mild to moderate proteinuria and normal to mildly reduced GFR who were normotensive, nondyslipidemic, and cardiovascular-events free were enrolled. None of the patients was taking metformin or renin-angiotensin system blockers.
FMD was inversely related with Hb levels. Furthermore, there was an inverse link between proteinuria and FMD. However, further analysis of this association showed that the FMD-proteinuria link was confined to patients with proteinuria exceeding 150 mg/d, while no such association existed in patients with proteinuria <150 mg/d. Adjustment of the Hb-FMD relationship for pertinent Framingham risk factors, proteinuria, homeostasis model assessment (HOMA) index, and GFR levels had a modest influence on this association, which remained significant.
Endothelial function is inversely associated with Hb levels in diabetic patients with stage 1 to 2 CKD, and proteinuria is an effect modifier of this association. Overall, the observations of this study generate the hypothesis that proteinuria exposes a situation wherein Hb may limit the endothelium-mediated vasoregulation in diabetes.
Clinical Journal of the American Society of Nephrology 10/2009; 5(1):45-50. DOI:10.2215/CJN.05080709 · 4.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gynecomastia is defined as a palpable enlargement of the mammary gland in males that is distinguishable from lipomastia. The aim of this study was to assess the prevalence and characteristics of different causes of breast enlargement in young males referred to our tertiary center, and evaluation of the factors associated with gynaecomastia.
One hundred thirty-five male recruits aged 20-30 years were enrolled in the study. A control group comprising 32 age-matched healthy individuals aged 20-25 years was also studied.
Idiopathic gynecomastia (IG) was diagnosed in 31 of 135 patients (23%) and Klinefelter' syndrome (KS) was diagnosed in 70 cases (52%). Patients with KS had significantly higher body mass index (BMI) and waist and hip circumference waist/hip ratio than the control group. FSH, LH and SHBG were significantly higher and DHEAS, free testosterone (fT) and total testosterone (tT) were lower in patients with KS than the control group. Anthropometric measurements revealed significant increase in body weight and BMI in patients with IG compared with healthy controls. FSH and LH levels were significantly higher in the patients with IG. Patients with pseudogynecomastia alone were not obese and hypogonadism was observed in 35.1% of patients.
We concluded that gynaecomastia in young adult males is mostly because of KS or idiopathic in origin. IG seems to be the result of androgen resistance and in part increased aromatization because of increased adiposity. Symptoms or findings for hypogonadism must be evaluated carefully in patients with pseudogynecomastia. We also suggest that the presence of both gynecomastia and azoospermia necessitate further karyotypic analyses for KS.
Irish Journal of Medical Science 07/2009; 179(4):575-83. DOI:10.1007/s11845-009-0345-1 · 0.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In clinical practice, the human chorionic gonadotrophin (hCG) stimulation test is widely used to evaluate testicular function. Inhibin B, a gonadal peptide regulating follice-stimulating hormone (FSH) secretion, is an established marker of Sertoli cell function and spermatogenesis in adults. The aim of this study was to determine whether basal inhibin B levels are able to predict testosterone response to hCG in idiopathic hypogonadotropic hypogonadism (IHH) patients and to evaluate the correlation between inhibin B and gonadotropins in these patients and controls. Inhibin B (n=15) and other hormones (n=29) were measured in 29 patients with IHH and 32 controls. Inhibin B (n=8) and testosterone levels (n=25) before and after hCG stimulation were measured in 25 male patients with IHH by an immunoassay specific for inhibin B. Basal inhibin B was compared to the testosterone increase after hCG. There was a significant increase in inhibin B (22.6 +/- 9.8 vs 45.07 +/- 13 pg/mL; p=.005), free testosterone (2.92 +/- 0.55 vs. 7.9 +/- 1.5 pg/mL; p=.002), and total testosterone (69.0 +/- 15.9 vs. 184.9 +/- 44.1 ng/mL; p = .013) levels 72 hours after hCG injection. Inhibin B and the hCG-induced free testosterone and total testosterone increment correlated strongly (r=0.802, P<.001; r=0.793, P<.001, respectively). We conclude that basal inhibin B predicts the testosterone response to hCG in IHH patients and therefore gives reliable information about Leydig cell reserve. Furthermore, inhibin B levels show negative correlation with luteinizing hormone (LH) in control patients and positive correlation with FSH and LH in IHH patients. LH may effect inhibin B secretion. Further studies are necessary to define the physiology of inhibin B in human males.
Journal of the National Medical Association 01/2009; 101(1):71-6. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of growth hormone are mediated in part by stimulating the production of insulin-like growth factor-1. Insulin-like growth factor-1 has significant effects on cell proliferation and differentiation, it is a potent mitogen, and it is a powerful inhibitor of programmed cell death (apoptosis). Insulin-like growth factor-1 also has a well-established role in the transformation of normal cells to malignant cells. Case reports on a possible association between elevated growth hormone and cancer risk in a variety of patient groups have been published. Here, we describe clinical and laboratory findings for a patient with acromegaly who first developed thyroid cancer, and then, in the follow up period, probably due to poorly controlled insulin-like growth factor-1 levels, developed a large cell non-Hodgkin's lymphoma. A search revealed that a case with these peculiarities had not previously been reported.
Medical Oncology 08/2008; 26(1):62-6. DOI:10.1007/s12032-008-9084-9 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Whether to treat subclinical hypothyroidism (SH) remains controversial. Serum chitotriosidase activity, a marker of activated macrophages, predicts new cardiovascular events. Chitotriosidase activity (ChT) is a new cardiovascular risk marker and is independent of C-reactive protein. The purpose of this study was to determine ChT levels in SH and to examine the effect of levothyroxine replacement on ChT.
A cohort of 60 patients with subclinical hypothyroidism and 62 healthy controls were enrolled in this study. Serum total and LDL cholesterol, total homocysteine (t-Hyc), highly sensitive C-reactive protein (hsCRP) levels and serum ChT in patients with subclinical hypothyroidism at baseline and after achieving euthyroid state by levothyroxine were assessed.
Pretreatment levels of TSH (10.06+/-5.09 vs. 2.08+/-0.95 mIU/L, p<0.05), and free T4 (0.94+/-0.21 vs. 1.35+/-0.26 ng/dl, p<0.05) were significantly higher than controls while total cholesterol, LDL cholesterol, t-Hyc, ChT and hsCRP levels were not different. ChT levels significantly increased after replacement therapy (137.2+/-14.18 vs. 156.88+/-13.10 nmol/mL/h, p<0.05). T-Hyc and hsCRP levels were not significantly different after treatment with levothyroxine therapy even in this subgroup of patients. None of the other biochemical risk factors improved after euthyroidism in patients with SH with average dose of 85+/-30 mug/day when compared to pretreatment levels.
We conclude that clinical management of subclinical hypothyroidism does not decrease the serum hsCRP or t-Hyc levels but does increase the serum ChT levels. The clinical significance of this increment should be studied in further studies.
Internal Medicine 01/2008; 47(14):1309-14. DOI:10.2169/internalmedicine.47.1013 · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Type 1 (distal) and type 2 (proximal) renal tubular acidosis (RTA) are uncommon disorders, particularly in adults. HDR syndrome (hypoparathyroidism, sensorineural deafness and renal disease) is an autosomal dominant condition, defined by the triad hypoparathyroidism, renal dysplasia and hearing loss. Here, we describe a 19-year-old man with HDR syndrome accompanied by renal tubular acidosis and endocrinopathic changes.
Internal Medicine 01/2008; 47(11):1003-7. DOI:10.2169/internalmedicine.47.0917 · 0.90 Impact Factor