Quantitative ultrasound techniques and biochemical markers to assess liver steatosis and fibrosis in newly diagnosed acromegaly.

PURPOSE: The liver is known to be protected from steatosis under the influence of high GH/IGF-1. Cytokeratin 18 (CK18) and insulin-like growth factor binding protein 7 (IGFBP7) increase in liver steatosis and fibrosis. The aim of this study was to use quantitative ultrasound techniques and biochemical markers to assess liver steatosis and liver fibrosis in newly diagnosed acromegaly. METHODS: This single-center, cross-sectional study included 23 patients with newly diagnosed acromegaly and 46 age, sex, body mass index (BMI) and waist circumference (WC)-matched controls. Liver steatosis was assessed using tissue attenuation imaging (TAI), and stiffness, indicative of fibrosis, was assessed by shear wave elastography (SWE). Serum IGFBP7 and CK18 were studied by ELISA. RESULTS: The acromegaly group had significantly lower liver steatosis (p = 0.006) and higher liver stiffness (p = 0.004), serum IGFBP7 (p = 0.048) and CK18 (p = 0.005) levels than the control group. The presence of fibrosis (p = 0.012) was significantly higher in the acromegaly group than in the control group. Moreover, CK18 was positively correlated with liver stiffness, WC, HOMA-IR, HbA1c, and triglyceride. In the acromegaly group, liver steatosis was negatively correlated with GH level. Stepwise multiple linear regression analysis revealed that BMI (p = 0.008) and CK18 (p = 0.015) were independent risk factors for increased liver stiffness. CONCLUSION: This study showed that there was an increased presence of liver fibrosis independent of liver steatosis in newly diagnosed acromegaly. Serum CK18 appears to be a potential marker of increased liver fibrosis in acromegaly.

Antithyroid drugs in Graves' hyperthyroidism: differences between "block and replace" and "titration" regimes in frequency of euthyroidism and Graves' orbitopathy during treatment.

PURPOSE: Whereas antithyroid drugs (ATD) are the preferred treatment modality for Graves' hyperthyroidism (GH), there is still controversy about the optimal regimen for delivering ATD. To evaluate whether 'Block and Replace' (B + R) and 'Titration' (T) regimes are equivalent in terms of frequency of euthyroidism and Graves' Orbitopathy (GO) during ATD therapy. METHODS: A prospective multicentre observational cohort study of 344 patients with GH but no GO at baseline. Patients were treated with ATD for 18 months according to B + R or T regimen in line with their institution's policy. RESULTS: Baseline characteristics were similar in both groups. In the treatment period between 6 and 18 months thyrotropin (TSH) slightly increased in both groups, but TSH was on average 0.59 mU/L (95% CI 0.27-0.85) lower in the B + R group at all time points (p = 0.026). Serum free thyroxine (FT4) remained stable during the same interval, with a tendency to higher values in the B + R group. The point-prevalence of euthyroidism (TSH and FT4 within their reference ranges) increased with longer duration of ATD in both groups; it was always higher in the T group than in the B + R group: 48 and 24%, respectively, at 6 months, 81 and 58% at 12 months, and 87 and 63% at 18 months (p < 0.002). There were no significant differences between the B + R and T regimens with respect to the fall in thyrotropin binding inhibiting immunoglobulins (TBII) or thyroid peroxidase antibodies (TPO-Ab). GO developed in 15.9% of all patients: 9.1 and 17.8% in B + R group and T group, respectively, (p = 0.096). GO was mild in 13% and moderate-to-severe in 2%. CONCLUSION: The prevalence of biochemical euthyroidism during treatment with antithyroid drugs is higher during T compared to B + R regimen. De novo development of GO did not differ significantly between the two regimens, although it tended to be higher in the T group. Whether one regimen is clinically more advantageous than the other remains unclear.

Asymmetry indicates more severe and active disease in Graves' orbitopathy: results from a prospective cross-sectional multicentre study.

PURPOSE: Patients with Graves' orbitopathy can present with asymmetric disease. The aim of this study was to identify clinical characteristics that distinguish asymmetric from unilateral and symmetric Graves' orbitopathy. METHODS: This was a multi-centre study of new referrals to 13 European Group on Graves' Orbitopathy (EUGOGO) tertiary centres. New patients presenting over a 4 month period with a diagnosis of Graves' orbitopathy were included. Patient demographics were collected and a clinical examination was performed based on a previously published protocol. Patients were categorized as having asymmetric, symmetric, and unilateral Graves' orbitopathy. The distribution of clinical characteristics among the three groups was documented. RESULTS: The asymmetric group (n = 83), was older than the symmetric (n = 157) group [mean age 50.9 years (SD 13.9) vs 45.8 (SD 13.5), p = 0.019], had a lower female to male ratio than the symmetric and unilateral (n = 29) groups (1.6 vs 5.0 vs 8.7, p < 0.001), had more active disease than the symmetric and unilateral groups [mean linical Activity Score 3.0 (SD 1.6) vs 1.7 (SD 1.7), p < 0.001 vs 1.3 (SD 1.4), p < 0.001] and significantly more severe disease than the symmetric and unilateral groups, as measured by the Total Eye Score [mean 8.8 (SD 6.6) vs 5.3 (SD 4.4), p < 0.001, vs 2.7 (SD 2.1), p < 0.001]. CONCLUSION: Older age, lower female to male ratio, more severe, and more active disease cluster around asymmetric Graves' orbitopathy. Asymmetry appears to be a marker of more severe and more active disease than other presentations. This simple clinical parameter present at first presentation to tertiary centres may be valuable to clinicians who manage such patients.

Association of serum betatrophin with fibroblast growth factor-21 in women with polycystic ovary syndrome.

PURPOSE: Betatrophin and fibroblast growth factor-21 (FGF-21), which are recently discovered members of hepatokine/adipokine family, have been proposed to be associated with some metabolic disorders in which insulin resistance plays a major role. METHODS: We aimed to investigate serum betatrophin and FGF-21 concentrations in women with polycystic ovary syndrome (PCOS). In this cross-sectional study, we recruited 31 women with PCOS and 34 women as healthy controls. Serum betatrophin level and its relationship with serum FGF-21 level as well as metabolic parameters were examined. RESULTS: Serum betatrophin level was significantly higher in women with PCOS than the control group [1.10 (0.20-4.20) vs 0.70 (0.20-3.50) ng/ml, p = 0.004], whereas FGF-21 did not differ between the groups [74.80 (7.80-435.90) vs 119.30 (10.50-443.40) pg/ml, p = 0.13]. Serum betatrophin correlated positively with LH levels (r = 0.26, p = 0.03). After controlling BMI, there was a significant positive correlation between betatrophin and FGF-21 (r = 0.25, p = 0.04). Multivariate regression analysis revealed that FGF-21 and presence of PCOS were the significant predictors of betatrophin concentrations (R2 = 0.22, F = 2.56, p = 0.03). CONCLUSIONS: Our results indicate that betatrophin levels are increased and associated with LH and FGF-21 levels, but not with insulin resistance, in women with PCOS.

Graves' orbitopathy as a rare disease in Europe: a European Group on Graves' Orbitopathy (EUGOGO) position statement.

BACKGROUND: Graves' orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682). The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare. Recent published data on the incidence of GO and Graves' hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves' Orbitopathy. The prevalence of GO in Europe is about 10/10,000 persons. The prevalence of other clinical variants is also low: hypothyroid GO 0.02-1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with acropachy 0.03/10,000; asymmetrical GO 1.00-5.00/10,000; unilateral GO 0.50-1.50/10,000. CONCLUSION: GO has a prevalence that is clearly above the threshold for rarity in Europe. However, each of its clinical variants have a low prevalence and could potentially qualify for being considered as a rare condition, providing that future research establishes that they have a distinct pathophysiology. EUGOGO considers this area of academic activity a priority.

SERUM OMENTIN-1 LEVELS AND ENDOTHELIAL DYSFUNCTION IN OBESITY.

INTRODUCTION: Our aim was to investigate the relationship between serum omentin-1 levels and endothelial dysfunction in obese patients. MATERIAL AND METHODS: We evaluated 50 obese patients, and age/gender matched 45 healthy non-obese subjects as controls. Oral glucose tolerance test, lipid parameters, uric acid levels, homeostatic model assessment-insulin resistance (HOMA-IR) index, serum omentin-1 levels and flow mediated dilatation (FMD) % were measured in all subjects. Body compositions were analyzed with bioelectrical impedance method using a Tanita Body Composition Analyzer and ViScan. RESULTS: Serum omentin-1 levels were found significantly lower in obese population compared to the control subjects. FMD response was significantly decreased in obese population. There was a significant positive correlation between serum omentin-1 levels and FMD response (r=0.359, p<0.001). Serum omentin-1 levels were negatively correlated with body mass index (BMI), waist circumference, total fat percentage, visceral fat, fasting insulin and HOMA-IR index. CONCLUSION: Lower serum omentin-1 levels and decreased FMD response may be an early marker of endothelial dysfunction in obese patients.

THYROID MALIGNANCY RISK OF INCIDENTAL THYROID NODULES IN PATIENTS WITH NON-THYROID CANCER.

CONTEXT: Thyroid incidentaloma is a common disorder in endocrinology practice. Current literature regarding the risk of thyroid cancer in incidentalomas found in patients with non-thyroid cancer is limited. OBJECTIVE: The aim of the present study was to investigate the frequency of thyroid malignancy in thyroid incidentalomas detected in patients with non-thyroid cancer. DESIGN: Case control study. SUBJECTS AND METHODS: The database of 287 thyroid nodules from 161 patients with a history of non-thyroid cancer followed between 2008 and 2014 were retrospectively evaluated. RESULTS: From 287 thyroid nodules, 69.7 % had a benign final cytology. Thyroid cancer detected in one nodule while follicular neoplasia detected in 4 nodules, atypia of unknown significance (AUS) detected in 10 nodules, Hurthle cell neoplasia detected in 5 nodules and suspicious for malignancy detected in 6 nodules according to fine needle aspiration biopsy results. Metastasis of the non-thyroid cancer to the thyroid gland was detected in 4 nodules. Twenty seven nodules from 15 patients were removed with surgery. There were 3 malignant nodules found after surgery (1 papillary, 1 follicular and 1 medullary cancer). In addition to these three thyroid cancers, two patients with benign nodules had co-incidental thyroid cancer detected after surgery. Finally, 11.1 % of thyroid nodules which underwent thyroid surgery had malignant histopathology except for co-incidental and metastatic cancers. CONCLUSIONS: The frequency of thyroid malignancy seems not to be substantially increased in incidental thyroid nodules detected in patients with non-thyroid cancer when these patients were evaluated in nodule-based approach.

Cardiac structure and functions in patients with asymptomatic primary hyperparathyroidism.

BACKGROUND: The data about cardiovascular (CV) changes in patients with asymptomatic primary hyperparathyroidism (PHPT) are scarce. AIM: The aim of this study is to compare cardiac structure and functions in patients with asymptomatic PHPT and controls by using tissue Doppler echocardiography. SUBJECTS AND METHODS: Thirty-eight patients with asymptomatic PHPT and 31 sex- and age-matched controls with similar cardiac risk factors were evaluated. RESULTS: There was no significant difference in ejection fraction (EF) between the patients and the controls [64±5.95 vs 62±3.25% (p=0.094)]. Left ventricular mass index (LVMI) was significantly higher in patients than controls [105.96 (66.45-167.24) vs 93.79 (64.25- 139.25) g/m2, p=0.014]. There was a significant correlation between LVMI and serum calcium (Ca) (r=0.240, p<0.005). Myocardial performance index (MPI) was significantly higher in patients than controls [0.49 (0.35-0.60) vs 0.39 (0.33-0.62), p<0.001]. There was positive correlation between theMPI and serumCa levels (r=0.505, p<0.001), parathyroid hormone (PTH) levels (r=0.464, p<0.001) and LVMI (r=0.270, p<0.005). When the normotensive patients and controls were evaluated, the difference between the groups remained statistically significant considering LVMI and MPI [109 (66.45-167.24) g/m2 vs 94.17 (64.25-75.10) g/m2, p=0.03; and 0.49 (0.35-0.60) vs 0.39 (0.33-0.62), p<0.01, respectively]. There were significant correlations between MPI and Ca (r=0.566, p<0.001), and PTH (r=0.472, p<0.001). CONCLUSIONS: Our study results showed that cardiacmorphology and diastolic functions are altered in the patients with asymptomatic PHPT. High serum PTH and Ca levels may have an impact on these CV changes. Whether these subtle CV changes would affect cardiac systolic functions and mortality in patients with asymptomatic PHPT should be investigated in further prospective studies.

Association of polymorphisms in the IL-18 and IL-12 genes with susceptibility to Type 1 diabetes in Turkish patients.

BACKGROUND: Recent studies have indicated that polymorphisms of the interleukin-18 (IL-18) and interleukin- 12 (IL-12) genes are associated with the development of Type 1 diabetes mellitus (T1DM) in some populations, but not all. AIM: The present study was designed to examine the roles of polymorphisms in the IL-18 promoter and IL-12p40 with respect to susceptibility to T1DM in Turkish patients. SUBJECTS AND METHODS: Ninety-one patients with T1DM and 87 unrelated healthy subjects were included in the study. The IL-18 polymorphisms at positions -607 and -137 were detected by a sequence-specific PCR method. The single nucleotide polymorphism in the IL-12p40 3' untranslated region (3'-UTR) at position +1188 was analyzed by the PCR-restriction fragment length polymorphism (RFPL) method. RESULTS: The allelic and genotypic frequencies of the IL-18 and IL-12p40 polymorphisms did not differ significantly between subjects with T1DM and the controls (p>0.05). However, diabetic patients with the -137 (CC) genotype showed a younger onset age compared to patients with the -137 (GG) genotype (p=0.02). In addition, patients with the -607 (CC) genotype had higher levels of glycated hemoglobin (HbA1c) than patients with the -607 (AC) genotype (p=0.004). Furthermore, patients with the IL-12p40 (AC) genotype had higher HbA(1c) levels than patients with the IL-12p40 (AA) genotype (p=0.01). CONCLUSIONS: The results of the present study show that the IL- 18 and IL-12p40 polymorphisms may have some effect on the onset age and deterioration of glycemic control in Turkish patients with T1DM.

Plasma visfatin concentrations in subjects with type 1 diabetes mellitus.

BACKGROUND/AIMS: Visfatin is a recently discovered adipokine, and its circulating concentrations have not been adequately studied in type 1 diabetes mellitus (DM). Therefore, this study was designed to examine plasma visfatin levels in type 1 diabetic patients and to determine the relationships between visfatin and duration of diabetes, body mass index, glycemic control, insulin dosage and lipid profile. METHODS: Forty-eight patients with type 1 DM and 26 healthy controls were investigated. RESULTS: Type 1 diabetic patients had significantly low visfatin levels compared with controls (18.8 +/- 1.7 vs. 20.2 +/- 0.3 ng/ml; p < 0.0001). Visfatin levels were comparable between patients with a short duration of diabetes (<10 years) and patients with a long duration of diabetes (>or=10 years) (18.9 +/- 1.7 vs. 18.2 +/- 2.0 ng/ml; p > 0.05). There was a significant correlation between visfatin and hemoglobin A1c (HbA1c) even after the adjustment for age, sex, body mass index and duration of diabetes (r = -0.48, p = 0.005) in the patient group. Multivariate analysis showed that significant determinants of visfatin concentrations were HbA1c and duration of diabetes (r(2) = 0.27). CONCLUSION: These data emphasize that plasma visfatin concentrations are lower in patients with type 1 DM and related to glycemic control reflected by HbA1c.

Atherogenic lipoprotein phenotype and LDL size and subclasses in women with gestational diabetes.

AIMS: Women with gestational diabetes are more likely to develop Type 2 diabetes and cardiovascular disease after pregnancy; however, the exact nature of the lipid alterations present is not clear. In Mediterranean women with gestational diabetes, we measured low-density lipoprotein (LDL) size and all seven subclasses, as well as the 'atherogenic-lipoprotein phenotype'[ALP, e.g. concomitant presence of elevated triglycerides, reduced high-density lipoprotein (HDL)-cholesterol and increased small, dense LDL]. METHODS: In 27 women with gestational diabetes and 23 healthy pregnant women matched for age, weeks of gestation and body mass index, we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis between 24 and 28 weeks of gestation. RESULTS: Although no significant differences were found in the concentrations of any of the plasma lipids, compared with control subjects women with gestational diabetes had lower LDL size (P = 0.0007) due to reduced LDL-I (P = 0.0074) and increased LDL-IVA (P = 0.0146) and -IVB (P < 0.0001) subclasses. Correlation analysis revealed that fasting glucose, homeostasis model assessment and glycated haemoglobin were inversely correlated with LDL-I and positively with LDL-IVA and -IVB (all P < 0.05). ALP due to high HDL-cholesterol levels was not seen in either group, whereas elevated small, dense LDL were more common in women with gestational diabetes than control subjects (33% vs. 4%, P = 0.0107). CONCLUSIONS: Increased levels of small, dense LDL are common in Mediterranean women with gestational diabetes. Whether these findings affect the atherogenic process and clinical end-points in these women remains to be determined by future prospective studies.

The association of neurofibromatosis, bilateral pheochromocytoma and primary hyperparathyroidism.

Neurofibromatosis (NF) is a hereditary disease and carries increased risk of both benign and malignant tumor development. Pheochromocytoma or hyperparathyroidism have been reported to be associated with NF type 1 (NF1). However, the coexistance of pheochromocytoma and parathyroid adenoma in a patient with NF1 is very rare. We report a case of a 37-year-old male with NF1, bilateral pheochromocytoma and parathyroid adenoma. This association sould be kept in mind in patients with NF1 in initial evaluation as well as during follow-up.

Gait deviations of patients with diabetes mellitus: looking beyond peripheral neuropathy.

AIM: The aim of this paper was to define the gait deviations in patients with diabetes mellitus (DM), to investigate the associations between electrophysiological findings and gait characteristics, and to interpret the findings in preventive and therapeutic rehabilitation protocols. METHODS: Forty-six patients with DM and 20 healthy control subjects were enrolled into this controlled study. Electrophysiological studies and computerized gait analysis were performed. Gait deviations of DM patients with diabetic peripheral neuropathy (DPN) (n=20), without diabetic peripheral neuropathy (NDPN) (n=26) and healthy control subjects (C) (n=20) were compared, and associations between electrophysiological findings and gait characteristics were investigated. RESULTS: NDPN, but not DPN, group revealed slower gait, shorter steps, limited knee and ankle mobility, lower ankle plantar flexor moment and power than C group, and the difference was statistically significant. HbA1c levels and F-wave latency were significantly correlated with ankle mobility, peak ankle plantar flexion moment and power. CONCLUSION: Neuropathy may not be the only reason for gait deviations in DM patients. Considering the spectrum of hyperglycemic complications including the mechanical characteristics of bones, muscles and soft tissues, patients with DM should start mobility and strengthening exercises in early stages.

The effects of rosiglitazone and metformin on insulin resistance and serum androgen levels in obese and lean patients with polycystic ovary syndrome.

AIM: The aim of this study was to assess the effects of metformin and rosiglitazone on insulin resistance and serum androgen levels in both obese and lean patients with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: Forty lean [body mass index (BMI) < 25 kg/m2] and 40 overweight and obese (BMI > 25 kg/m2) patients were included in the study. Waist and hip measurements, serum sex steroid levels, insulin response to 75-g oral glucose tolerance test, fasting insulin, fasting C-peptide levels and homeostasis model assessment of insulin resistance (HOMA-IR) were determined in all patients. The degree of hirsutism was determined by the Ferriman-Gallwey scoring system. Patients were divided into two groups, with 40 (20 overweight and obese; 20 non-obese) patients each. One group was treated with metformin (MET group) 850 mg bid while the other received rosiglitazone (ROSI group) 4 mg/day for 12 weeks. All measurements were repeated at the end of this period. RESULTS: After the 12-week treatment period, HOMA-IR, area under the curve of insulin, fasting insulin and C-peptide levels were observed to have be decreased significantly in all groups. The decrease in the parameters mentioned above was similar in the four groups. The serum levels of free testosterone, androstenedione and DHEA-S decreased in all groups, but the decrease was statistically significant only in the ROSI groups. Within the lean MET group one patient became pregnant and was hence excluded from the final data analysis. Menstruations became regular after metformin therapy in 41.6% of lean and 35.7% of obese patients who had menstrual disturbance prior to the study. Rosiglitazone therapy improved menstrual disturbance in 61.5 % of lean and 53.8% of obese patients. CONCLUSIONS: Our data showed that both metformin and rosiglitazone increased insulin sensitivity in obese patients with PCOS as expected, and in lean patients as well. Rosiglitazone seemed to be more effective in decreasing the androgen levels and in achieving slightly greater improvement in menstrual disturbance than metformin.

Effects of PPARgamma and PPARalpha agonists on serum leptin levels in diet-induced obese rats.

Leptin and peroxisome proliferator-activated receptors are two important adipose tissue factors involved in energy metabolism regulation. It has been shown that PPARgamma agonists decrease leptin levels. However, the effects of PPARalpha agonists on leptin have not been investigated much. The aim of this study was to compare the effects of a PPARgamma agonist rosiglitazone (RSG) and PPARalpha agonist gemfibrozil (G) on body weight and serum insulin and leptin levels in diet-induced obese rats. Male Wistar rats were divided into six groups according to diet and drug therapy. After four weeks, serum glucose, triglyceride, insulin and leptin levels were significantly decreased in the high-fat-fed and RSG-treated groups compared to the group fed a high-fat diet only (162 +/- 19 vs. 207 +/- 34 mg/dl, 58 +/- 20 vs. 112 +/- 23 mg/dl, 3.1 +/- 1.0 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.5 vs. 3.6 +/- 1.6 ng/ml, respectively). However, these parameters were not statistically different in RSG animals treated with a standard diet compared to the standard diet group. The high fat+RSG group gained much more weight compared to high-fat and high-fat+G groups (p > 0.05). Additionally, serum glucose, insulin and leptin levels were significantly decreased in the high-fat-fed and G-treated group compared to high-fat group (149 +/- 19 vs. 207 +/- 34 mg/dl, 57 +/- 16 vs. 112 +/- 23 mg/dl, 4.3 +/- 2.1 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.4 vs. 3.6 +/- 1.6 ng/ml, respectively). These results suggest that PPARalpha agonists may decrease serum glucose, insulin and leptin levels as PPARgamma agonists do in diet-induced obese rats.

Treatment effect of sibutramine compared to fluoxetine on leptin levels in polycystic ovary disease.

Weight reduction on its own is observed to cause improvement in some of the abnormalities seen in patients with polycystic ovary syndrome (PCOS). With respect to this observation, we studied the possible effects of different serotonin reuptake inhibitors (fluoxetine and sibutramine) on serum leptin levels that might play a role in the obesity component seen in patients with PCOS. In a random design, sixteen patients were assigned to fluoxetine and sibutramine for a period of 10 days. In both treatment groups, no significant differences were observed between pre-treatment and post-treatment values in insulin levels (p > 0.05). There was no significant difference between pretreatment and post-treatment serum leptin levels in the fluoxetine treatment group (p > 0.05). However, a significant reduction was observed in the serum leptin levels at the end of treatment in the sibutramine group (p < 0.05). The observed difference in the serum leptin response to the treatment effect of sibutramine compared to fluoxetine seems to be due to a mechanism independent of serotonin reuptake inhibition, possibly to the thermogenic effect of the sibutramine itself. Further studies with larger groups are warranted, to examine the mechanism of the weight-reducing effect of sibutramine. Detailed analyses of basal metabolic activity and change in serum leptin levels should be carried out.

The relationship between levels of alpha1-acid glycoprotein and metabolic parameters of diabetes mellitus.

The aim of this study was to investigate the relationship of alpha1-acid glycoprotein (AGP, orosomucoid), which is an acute-phase reactant, in patients with Type 1 (T1DM) and Type 2 diabetes mellitus (T2DM), with the metabolic parameters and complications of diabetes mellitus. A total of 119 diabetic patients (89 T2DM, 30 T1DM) and 33 healthy controls were included in the study. The mean AGP level in the diabetic group was not different from the control group (82.4 +/- 28.9 and 81.6 +/- 16.6 mg/dl, respectively), but it was higher in T2DM than in T1DM subjects (86.6 +/- 28.3 and 69.7 +/- 26.9, respectively). AGP plasma levels showed a significant correlation with age and body mass index (r = +0.348 and r = +0.296, respectively). AGP plasma levels resulted higher in obese diabetic patients (97.7 +/- 28.0) than in non-obese diabetic patients (77.6 +/- 28.7 mg/dl) and controls (81.6 +/- 16.6), and also higher in diabetic subjects with poor glycaemic control (85.1 +/- 33.3 mg/dl) than in diabetic subjects with optimal glycaemic control (79.5 +/- 23.1 mg/dl). A relationship between AGP and macro- and microvascular complications of diabetes mellitus was not found. In conclusion, inflammatory findings were more prominent in obese diabetic patients.

Insulin secretion and insulin sensitivity in normal pregnancy and gestational diabetes mellitus.

The purpose of this study was to evaluate insulin sensitivity, beta-cell function and islet-cell-directed autoimmunity in pregnant women with normal glucose tolerance and gestational diabetes mellitus (GDM). A total of 21 women with normal glucose tolerance and 21 women with GDM were evaluated at 24-36 weeks' gestation. Insulin resistance and beta-cell function were evaluated using the continuous infusion of glucose with model assessment (CIGMA) method, which aims to give a near-physiological stimulus and to evaluate the endogenous insulin and glucose response. Islet-cell autoantibody was positive in one woman with GDM, and glutamic acid decarboxylase autoantibodies were negative in both groups. The calculated CIGMA insulin resistance (CIGMA IR) was 2.04 +/- 1.74 and 1.08 +/- 1.22 in patients with GDM and in control subjects, respectively (p < 0.05). CIGMA percentage beta-cell values were 64.04 +/- 44.55% and 87.07 +/- 52.77% in patients with GDM and control subjects, respectively (p > 0.05). Decreased insulin sensitivity in late pregnancy was more evident in lean GDM subjects with mild hyperglycemia who did not require insulin therapy, and beta-cell function was partially preserved in this group of patients.

Serum leptin, prolactin and vascular endothelial growth factor (VEGF) levels in patients with breast cancer.

Angiogenesis plays an important role in tumor growth and metastasis in solid tumors. VEGF is an important regulator of tumor angiogenesis. Both leptin and prolactin have also been suggested to have roles in the regulation of angiogenic process. In our study, we measured serum leptin, prolactin and VEGF levels in 30 metastatic, 55 non-metastatic breast cancer patients and 25 control subjects. Serum leptin levels were found to be similar in non-metastatic (38.1+/-19.5 ng/ml), metastatic patients (39.6+/-16.3 ng/ml) and control subjects (35.6+/-13.9 ng/ml) (p>0.05). There was no statistically significant difference between patients with visceral metastasis (44.0+/-16.8 ng/ml) and patients with bone metastasis (35.2+/-15.0 ng/ml) (p>0.05). Serum prolactin levels were found to be similar in non-metastatic (12.2+/-10.7 ng/ml), metastatic patients (11.6+/-8.2 ng/ml) and control subjects (12.3+/-8.1 ng/ml), (p>0.05). Moreover, serum prolactin levels were not different in patients with visceral (11.4+/-8.8 ng/ml) and bone metastasis (11.8+/-8.0 ng/ml), (p>0.05). Metastatic patients had higher serum VEGF levels (249.8+/-154.9 pg/ml), when compared to the non-metastatic patients (138.7+/-59.3 pg/ml) and control subjects (108.4+/-47.7 pg/ml), (p<0.05). There was no difference in serum VEGF levels in non-metastatic patients and control subjects (p>0.05). Patients with visceral metastasis (337.0+/-168.0 pg/ml) had higher serum VEGF levels, when compared to patients with bone metastasis (162.6+71.8 pg/ml), (p<0.05). Serum VEGF activity may be used to evaluate angiogenic and metastatic activity in breast cancer patients. However, serum leptin and prolactin levels does not seem to be related with angiogenic activity and metastasis in breast cancer patients.

Tamoxifen therapy and hepatic steatosis.

Tamoxifen has been used for a long time as a hormonal treatment in breast cancer. Recent studies in pre and postmenopausal women have shown that tamoxifen exhibits favorable effects on the lipid profile. In this study we investigated the effects of tamoxifen on lipid profile and hepatic steatosis. Fifty two (31 postmenopausal and 21 premenopausal) women with breast cancer treated with tamoxifen at a dose of 20 mg daily were included in the study. Serum lipid parameters (total cholesterol, high and low density lipoprotein cholesterol and triglyceride) were measured baseline and at the 6th month of tamoxifen treatment. Upper abdominal ultrasonography was performed before and at the 6th month of therapy for assessment of liver steatosis. We obtained decreased levels of serum total cholesterol after 6 months of tamoxifen treatment (p < 0.05). However, we did not detect any changes in triglyceride and high-density lipoprotein cholesterol levels (p > 0.05). Increased liver steatosis was observed in 22 patients (42.3%) after tamoxifen treatment. We could not detect increase in lipid levels in these patients. There was no significant difference between the lipid levels in the patients with increased liver steatosis and stable or no liver steatosis. Whether hepatic steatosis is dependent on lipid changes in tamoxifen use should be further investigated.