The effects of rosiglitazone and metformin on inflammation and endothelial dysfunction in patients with type 2 diabetes mellitus.

Diabetic patients have a markedly increased risk of cardiovascular disease compared with non-diabetics. Two drug groups today target insulin resistance; biguanides and thiazolidinediones. In addition, these may have other effects on cardiovascular risk factors. The aim of this study was to evaluate the effects of metformin and rosiglitazone on non-traditional cardiovascular risk factors. Forty type 2 diabetic patients were randomized into metformin and rosiglitazone groups. After receiving the optimal doses, the patients were monitored for 12 weeks. Biochemical parameters, lipid parameters, CRP, insulin, c-peptide, and HbA1c levels were analyzed. VWF, PAI-1, ICAM-1, TNF-α, IL-6, E-selectin, and fibrinogen levels were measured in order to assess coagulation status and endothelial dysfunction. In the metformin group, body mass index, PPG, HbA1c, IL-6, ICAM-1, and TNF-α levels were significantly decreased after 12 weeks compared with the basal levels. IL-6 levels decreased from 75 pg/ml ± 20 to 42 pg/ml ± 9 (P 0.023) and TNF- α levels from 61 pg/ml ± 31 to 39 pg/ml ± 10 (P 0.018). In the rosiglitazone group, FPG, PPG, HbA1c, insulin, HOMA-IR, IL-6, and TNF-α levels decreased significantly after 12 weeks compared with the basal levels. IL-6 levels decreased from 78 pg/ml ± 21 to 41 pg/ml ± 9 (P 0.028) and TNF-α levels from 62 pg/ml ± 19 to 37 pg/ml ± 10 (P 0.012). At the end of the study, no significant differences were determined between groups. Insulin resistance and type 2 diabetes are strongly associated with low grade inflammation. Both metformin and rosiglitazone were effective in controlling inflammatory markers in addition to metabolic parameters.

Blood coagulation and fibrinolysis in patients with Cushing's syndrome: increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels.

BACKGROUND AND OBJECTIVES: Cushing's syndrome (CS) is associated with an increased cardiovascular mortality and morbidity. Chronic endogenous and exogenous hypercortisolism frequently induce a hypercoagulable and thrombotic condition. Little is known about hemostatic features of patients with CS. To our knowledge, plasma tissue factor pathway inhibitor (TFPI) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels in these patients have not been investigated. Therefore, the main purpose of this study was to evaluate the markers of endogenous coagulation/fibrinolysis, including TFPI and TAFI, and to investigate the relationships between cortisol and these hemostatic parameters and serum lipid profile in patients with CS. DESIGN AND METHODS: Twenty-four patients with CS and 24 age-matched healthy controls were included in the study. Prothrombin time (PT), activated partial thromboplastin time (aPTT), 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), tissue plasminogen activator inhibitor-1 (PAI-1), TFPI and TAFI, as well as common lipid variables, were measured. The relationships between serum cortisol and these hemostatic parameters were examined. RESULTS: Compared with the control subjects, platelet count, PT, fibrinogen, AT-III and PAI-1 were significantly increased in patients with CS (p<0.05, p<0.0001, p<0.01, p<0.05, and p<0.0001, respectively), whereas aPTT and TFPI levels were significantly decreased (p<0.0001 and p<0.01, respectively). Plasma TAFI Ag levels did not significantly change in patients with CS compared with the controls. In patients with CS, we showed a negative correlation between serum cortisol: 08:00 h and aPTT (r:-0.469, p<0.05). Serum cortisol: 24:00 h was positively correlated with PAI-1 Ag levels (r: 0.479, p<0.05). INTERPRETATION AND CONCLUSIONS: In conclusion, we found some important differences in the hemostatic parameters between the patients with CS and healthy controls. Increased platelet count, fibrinogen, PAI-1, and decreased TFPI levels in these patients represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. This condition may contribute to the excess of mortality due to cardiovascular disease seen in patients with CS.

Neurofibromatosis type 1 associated with pheochromocytoma: a case report and a review of the literature.

Pheochromocytoma (PHEO) occurs in 0.1-5.7% of patients with neurofibromatosis type 1 (NF1). We report a case of adrenal PHEO in a patient with NF1. A 30-yr-old Turkish man was admitted to our hospital for further examinations of a right adrenal mass, that was incidentally discovered by abdominal ultrasonography during examinations for acute hepatitis B infection in another hospital. In his past medical history, the patient had only had one palpitation, sweating and headache episode 4 yr before. On admission, his blood pressure was 110/70 mmHg. Physical examination revealed signs of NF1. He had multiple neurofibromas over the entire skin, café-au-lait spots on the trunk and extremities and skinfold freckling. Bilateral opthalmic examination revealed multiple Lisch nodules. The 24-h ambulatory blood pressure monitoring revealed paroximal hypertension attacks (190/148 mmHg). Urinary catecholamines were markedly increased. Magnetic resonance imaging (MRI) revealed a solid round tumor approximately 5 cm in diameter, located in right adrenal gland. A 131Iodine-metaiodobenzylguanidine (131I-MIBG) scan showed uptake in the right adrenal gland. The pre-operative treatment with an alpha-blocker (phenoxybenzamine) was performed. Right adrenalectomy was performed; the surgical specimen revealed PHEO. Urine catecholamines and their metabolites returned to normal ranges on post-operative day 7. In conclusion, an adrenal mass can be incidentally discovered in any patient. After diagnosis of NF1, patients who have episodes of hypertension, sweating, headache and palpitation should be evaluated for PHEO.

The effects of losartan and fosinopril in hypertensive type 2 diabetic patients.

The aim of this study is to evaluate the effects of losartan on blood pressure (BP), creatinine clearance (Ccr) and urinary albumin excretion (UAE), and to assess metabolic parameters in comparison with ACEI. Thirty-three type 2 diabetic hypertensive patients were enrolled in the study. Twenty patients were randomized to receive 50 mg/day losartan and 13 patients to 10 mg/day fosinopril. Patients were studied at baseline and after 1 and 6 months. BP was significantly decreased in both groups at the end of the 1st and 6th month to a similar extent. Ccr had fallen in both groups at the end of 1st and 6th months. The effect of each drug on Ccr was similar (64.2+/-70.6 and 42.8+/-53.8 ml/min, respectively, NS). In the subgroup with microalbuminuria at baseline, UAE rate was lower in both groups at the end of the 1st and 6th months. However, when compared with the end of 1st month, the antiproteinuric effect of losartan was slightly decreased at the end of 6th month. Metabolic parameters did not change with either drug. Both drugs were well tolerated. Thus the antihypertensive effects of the two drugs were comparable. In conclusion, this study confirms the efficacy and safety of losartan as an antihypertensive drug in diabetic patients.