Comparison of effects of gliclazide, metformin and pioglitazone monotherapies on glycemic control and cardiovascular risk factors in patients with newly diagnosed uncontrolled type 2 diabetes mellitus.

OBJECTIVE: The objective of this study was to evaluate and compare the effects of gliclazide-modified release (gliclazide-MR), metformine (MET) and pioglitazone (PIO) monotherapies on glycemic control and conventional/non-conventional cardiovascular risk factors in patients with newly diagnosed type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: A single center, randomized, 52-wk comparator-controlled clinical study was carried out in patients with newly diagnosed uncontrolled T2DM. A total of 57 patients were randomized into gliclazide-MR, metformin and pioglitazone groups. Drugs were administered for 12 months. Anthropometric measurements, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), HbA1c, insulin, HOMA-IR, lipid parameters, the markers of coagulation/fibrinolysis, inflammation and endothelial dysfunction were measured at baseline and at months 3, 6, and 12. RESULTS: In the gliclazide-MR group, HC, FPG, HbA1c, insulin, HOMA-IR, TC, trigylcerides, Lp (a), E-selectin and Hcy were significantly decreased after treatment compared to baseline. In the MET group, BMI, WC, FPG, PPG, HbA1c, ICAM-1 and Hcy significantly decreased after treatment compared to baseline. In PIO group, WC, HC, FPG, PPG, HbA1c, C-peptid, HOMA-IR, trigylcerides, vWF, IL-6, ICAM-1, E-selectin and Hcy significantly decreased after treatment compared to baseline, whereas, HDL-C increased. At the end of the month 12, the decreases in insulin and HOMA-IR score were more pronounced with PIO compared to gliclazide. CONCLUSIONS: Gliclazide-MR, MET and PIO monotherapies, were equally effective in proving glycemic control in patients with newly diagnosed, oral antidiabetic (OAD)-naive T2DM. But, improvements in conventional/non-conventional cardiovascular risk factors were more pronounced in patients on PIO therapy compared to gliclazide and MET therapies. Also, all of the 3 drugs represent effective and safe first-line pharmacological treatment options in these patients.

Efficacy of low and high fixed dose radioactive iodine therapy in patients with toxic nodular goiter.

AIM: The efficacy of low and high fixed dose radioactive iodine (RAI) therapy in patients with toxic nodular goiter was investigated. METHODS: Ninety-three patients (25 males, 68 females) were included into the study (32 patients with toxic adenoma, 61 patients with toxic multinodular goiter). Patients were treated with a fixed dose of 370 MBq (10 mCi) or 740 MBq (20 mCi) RAI. The average follow-up period was 17±10 months. RESULTS: The overall cure rate (eutyhroidism and hypothyroidism) was 81% in patients treated with 740 MBq RAI and 51% in patients treated with 370 MBq RAI (p<0.05). RAI therapy with a dose of 370 MBq and 740 MBq provided the cure in 73% and 91% of the patients with toxic adenoma and 42% and 76% of the patients with toxic multinodular goiter, respectively. No significant difference for gender was observed. Hypothyroidism developed in 4 and 15 patients with a dose of 370 MBq and 740 MBq RAI, respectively. CONCLUSION: A dose of 740 MBq RAI was found to be more effective for the treatment of toxic nodular goiter as compared to a dose of 370 MBq RAI.

Blood coagulation, fibrinolysis and lipid profile in patients with primary hyperparathyroidism: increased plasma factor VII and X activities and D-Dimer levels.

BACKGROUND AND OBJECTIVES: Primary hyperparathyroidism (PHPT) is associated with an increased cardiovascular mortality and morbidity rate. However, the exact role of PTH and/or calcium in the development of cardiovascular disease (CVD) is still controversial. The influence of PHPT on hemostasis is yet unknown. Therefore, the main purpose of this study was to investigate the markers of endogenous coagulation/fibrinolysis and to evaluate the relationships between these hemostatic parameters, serum lipid profile and serum calcium and PTH in patients with PHPT. DESIGN AND METHODS: Twenty-three patients with PHPT and 20 age-matched healthy controls were included in the study. Fibrinogen, factors V, VII, VIII, IX and X activities, von Willebrand factor (vWF), antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipoprotein variables, were measured. The relationships between biochemical parameters and these hemostatic parameters were examinated. RESULTS: Compared with the control subjects, platelet count, FVII, FX activities, and D-Dimer levels were significantly increased in patients with PHPT (p<0.001, p<0.05, p<0.001, and p<0.05, respectively). Among the lipids, the levels of TC, TG and LDL-C were significantly increased in patients with PHPT (p<0.01, p<0.001, p<0.001, respectively) than those in controls. In patients with PHPT, we showed a positive correlation between urinary phosphorus excretion and factors VIII, IX, and X (r: 0.572, p<0.01; r: 0.543, p<0.01; r: 0.532, p<0.01, respectively). F IX activity was positively correlated with TC (r: 0.463, p<0.05) and LDL-C (r: 0.549, p<0.01) There was a positive correlation between serum ALP and PAI-1 levels (r: 0.451, p<0.05). ApoB was positively correlated with D-Dimer (r: 0.421, p<0.05). We did not find any significant correlation between iPTH and serum calcium and the hemostatic parameters that we measured. INTERPRETATION AND CONCLUSIONS: In conclusion, we found some important differences in the hemostatic parameters between the patients with PHPT and healthy controls. Increased platelet count, F VII and FX activities and D-Dimer levels in patients with PHPT represent a potential hypercoagulable state, which might augment the risk for atherosclerotic and atherothrombotic complications. This condition may contribute to the excess mortality rate due to CVD in patients with PHPT.

Subcutaneous lispro and intravenous regular insulin treatments are equally effective and safe for the treatment of mild and moderate diabetic ketoacidosis in adult patients.

In this prospective, randomised, open trial, we wanted to evaluate the efficacy and safety of hourly subcutaneous (SC) insulin lispro administration in the treatment of diabetic ketoacidosis (DKA) in comparison with intravenous (IV) regular insulin treatment. Twenty patients were enrolled in the study. The patients were randomly assigned into two groups. Following a bolus injection of 0.15 U/kg IV regular insulin, group L received half of this dose as hourly SC insulin lispro while group R was treated conventionally with IV regular insulin infusion. At the end of treatment period, time that needed for normalisation of serum glucose, beta-hydroxybutyrate, blood pH and urine ketone levels were not different in groups L and R. There was no mortality or serious side effects in both groups. In this study, we revealed that treatment of mild and moderate DKA with SC insulin lispro is equally effective and safe in comparison with IV regular insulin.

Pheochromocytoma combined with pre-clinical Cushing's syndrome in the same adrenal gland.

Pheochromocytoma (PHEO) occasionally associates with pathological lesions of the adrenal cortex. In most of them, ectopic adrenocorticotropic hormone (ACTH) produced by PHEO resulted in bilateral adrenocortical hyperplasia. The coexistence of PHEO and pre-clinical Cushing's syndrome (PCS) of the same adrenal gland has rarely been reported. We report on a patient and discuss the peculiar diagnostic aspects of this entity. A 52-yr-old Turkish woman was hospitalized at Farabi Hospital for further examinations of a right adrenal mass that was incidentally discovered by abdominal ultrasonography during examinations for abdominal bloating and "gas" in other hospital. The patient had a history of palpitations, nervousness, sweating and heat intolerance. On admission, her blood pressure was 140/90 mmHg. A physical examination revealed no signs of an excessive production of adrenocortical steroids such as in CS. Tension Holter monitoring revealed paroximal hypertension attacks (183/105 mmHg). Urinary catecholamines were markedly increased. Her serum cortisol concentrations ranged from 5 to 17 microg/dl, whereas ACTH levels were undetectable. Cortisol was not suppressed on the overnight 1 mg oral dexamethasone suppression test (DST), 2-day low-dose dexamethasone suppression test (DST). Abdominal computed tomography and magnetic resonance imaging studies revealed a solid round tumor approximately 4 cm in diameter, located in the right adrenal gland. A 131 lodine-metaiodobenzylguanidine (131 I-MIBG) scan revealed uptake within tumor in the right adrenal gland. Right adrenalectomy was performed; the surgical specimen revealed PHEO and adrenocortical hyperplasia. To our knowledge, the present report is a rare case of PHEO combined with PCS in the same adrenal gland.

QT dispersion in type 2 diabetic patients with altered diurnal blood pressure rhythm.

BACKGROUND: QT dispersion (QTd) is a good prognostic marker in type 2 diabetic patients without previous cardiovascular disease. Diabetic patients with an attenuated decline in nocturnal blood pressure (non-dippers) have been shown to have increased risk of diabetic complications, vascular events and mortality. AIM: The aim of this study was to evaluate the relationship between diurnal blood pressure rhythm, QTd and microvascular complications in type 2 diabetic patients. METHODS: Cardiovascular autonomic function tests, 24-h ambulatory blood pressure monitoring and urinary albumin excretion measurements were performed in healthy controls (n = 25), normoalbuminuric (n = 34) and microalbuminuric (n = 23) type 2 diabetic patients. QTd was assessed manually from 12-lead surface electrocardiograms. RESULTS: Compared with the controls, both normoalbuminuric and microalbuminuric diabetic patients had increased QTd (59.11 +/- 15.86; 60.27 +/- 17.95 vs. 40.48 +/- 10.92, p < 0.001 and p < 0.001, respectively). Similarly, diabetic patients had increased QTd regardless of the presence of autonomic neuropathy. On the other hand, non-dipper diabetic patients had increased QTd compared with the controls and dipper diabetic patients (69.73 +/- 14.50 vs. 40.48 +/- 10.92; 47.84 +/- 9.62 ms, p < 0.001). There was a negative correlation between QTd and diurnal diastolic blood pressure change (r = -0.48, p < 0.0005). CONCLUSION: Patients with type 2 diabetes mellitus were found to have increased QT dispersion irrespective of the presence of diabetic autonomic neuropathy. However, QT dispersion in dipper diabetic patients was similar to the controls. This finding might point out that attenuated decline of nocturnal blood pressure could be a more sensitive marker for autonomic neuropathy.

Effect of low-dose metoprolol in combination with sibutramine therapy in normotensive obese patients: a randomized controlled study.

OBJECTIVE: Sibutramine is an effective appetite suppresser agent, but treatment is often complicated with side effects, including palpitations and hypertension. In this study, we aimed to assess the effect of low-dose cardio-selective beta blocker combination with sibutramine treatment. METHODS: In total, 57 obese subjects were enrolled in the study and separated into two groups in order to receive sibutramine 10 mg/day plus placebo (group P) or sibutramine 10 mg/day plus metoprolol 25 mg/day (group M). Patients were evaluated in the beginning and at the end of the third month with anthropometric measurements, biochemical analysis, peripheral insulin resistance, and ambulatory 24 h blood pressure monitoring. Side effects were evaluated with a visual analog scale. RESULTS: During the study period, the drop-out rate was significantly higher in group P compared with group M (55 and 21%, respectively, P=0.014). Palpitations and headache were prominent symptoms in group P. Diastolic blood pressure (78.6+/-11.6 and 70.6+/-4.8 mmHg, respectively, P=0.013) and mean heart rate (84.3+/-6.1 and 75.8+/-8.4 beats/min, respectively, P=0.003) were significantly higher in group P compared with group M at the end of the third month. Weight loss was similar between the two groups (100.9+/-11.5 to 91.8+/-12.8 kg for group P, P<0.0001 and 97.9+/-13.2 to 88.9+/-13.8 kg for group M, P<0.0001). We did not find any deleterious effect of metoprolol on metabolic parameters. CONCLUSION: Addition of low-dose metoprolol to sibutramine therapy increased patient compliance to the treatment, and decreased the frequency and severity of side effects including hypertension and palpitations, without decreasing the drug efficacy or causing significant deleterious changes in metabolic parameters.

Blood coagulation and fibrinolytic activity in hypothyroidism.

The influence of hypothyroidism on haemostasis is controversial; both hypocoagulable and hypercoagulable states have been reported. Hypothyroidism has been associated with atherosclerosis; a hypercoagulable state in addition might represent a risk factor for thromboembolic disease. The aim of the present study was to investigate the markers of endogenous coagulation and vascular endothelial cell function and to evaluate the relationship between serum lipid profile, thyroid hormones and haemostatic parameters in hypothyroid patients. We investigated various haemostatic parameters in 20 patients with hypothyroidism and compared them with 20 euthyroid controls. The relationship between serum thyroid hormones and the haemostatic parameters was examined. The plasma levels of fibrinogen, AT III and PAI-1 were significantly increased in hypothyroid patients compared with the control group, whereas factors VIII and X activity was decreased. We showed that free T3 levels correlated with factor IX activity. Free T4, FT3 and TSH did not correlate with fibrinogen, vWF, AT III, t-PA, or PAI-1. aPTT correlated inversely with t-PA activity and positively with protein C activity. Anti-Tg correlated inversely with FV. There was a positive correlation between triglycerides and protein C. Protein S correlated inversely with high density lipoprotein cholesterol. We found a hypofibrinolytic state in patients with hypothyroidism. Our results suggest that the risk of developing thrombosis and ultimately myocardial infarction via high PAI-1 levels may be increased in patients with hypothyroidism, a result in line with recent epidemiological data. However, thyroid hormones may play a role at different levels of the complex haemostatic system.

Blood coagulation and fibrinolysis in patients with hyperthyroidism.

Several papers concerning abnormalities of blood coagulation and fibrinolysis during hyperthyroidism, have been published. Increased von Willebrand Factor (vWF) activity and high fibrinogen levels have been reported. However, there is controversy concerning the presence of a hypercoagulable state in hyperthyroidism. We investigated various hemostatic parameters in 41 hyperthyroid patients and compared them to 20 euthyroid controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors V, VII, VIII, IX and X activities, vWF, antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipid variables, were measured. The relationships between serum thyroid hormones and these hemostatic parameters were examined. Compared with control subjects, fibrinogen, factor IX, vWF, AT III and PAI-1 were significantly increased in patients (p<0.05, p<0.0001, p<0.05, p<0.01 and p<0.0001; respectively), whereas factor X and t-PA were decreased (p<0.05). We showed that free T4 (FT3) levels were correlated with factor VIII activity (r=0.35, p<0.05). FT4, FT3 and TSH did not correlate with fibrinogen, vWF, AT III, t-PA, or PAI-1. AT III was inversely correlated with factor VII activity (r=-0.48, p<0.01). Protein C and S were correlated with vWF levels (r=0.58, p<0.0001; r=0.55, p<0.0001, respectively). Protein C was inversely correlated with t-PA (r=-0.39, p<0.01). There was a negative correlation between triglycerides, LDL-C and F X (r=-0.45, p<0.05; r=-64, p<0.01, respectively). Mean platelet volume (MPV) was correlated with anti-thyroid peroxidase (TPO) antibodies (in Graves'disease) and F IX activity (r=0.57, p<0.05 and r=0.39, p<0.05; respectively). We found important differences in the coagulatory /fibrinolytic parameters between the hyperthyroid patients and healthy controls. Hyperthyroid patients may experience vascular endothelial dysfunction and decreased fibrinolytic activity in blood. This endothelial activation may represent a situation with a higher thromboembolic potential.

Effects of aminoguanidine on glomerular basement membrane thickness and anionic charge in a diabetic rat model.

We investigated the effect of aminoguanidine (AG) administration on GBM thickness, glomerular heparan sulfate (HS) content, and urinary albumin and HS excretion in diabetic rats. After induction of diabetes, female Wistar rats were divided into 2 groups: Group AGDM (n = 11) received 1 g/L aminoguanidine bicarbonate in drinking water, group DC (n = 12) was given only tap water. Control rats received AG (group AGH, n = 8) or tap water (group HC, n = 8). At the end of a period of 8 weeks, urinary albumin and glycosaminoglycan (GAG) excretion was detected. GBM heparan sulfate distribution and count was determined under the electron microscope. The AGDM group had lower urinary albumin and GAG excretion than diabetic controls. GBM thickness was increased in diabetic rats compared to groups of AGDM and HC. In AGDM group alcian blue stained particle distribution and count in the GBM was similar to healthy controls. In conclusion AG prevents the decrease of anionic charged molecules in the GBM and GBM thickening. This can be one of the mechanisms by which AG decreases albuminuria in diabetic rats.