Diagnostic and Treatment Monitoring Potential of Serum Vascular Endothelial Growth Factor-D in Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare multisystem disease occurring almost exclusively in premenopausal women and characterized by cystic lung destruction, abdominal tumors (renal angiomyolipomas (AML)), and involvement of the axial lymphatics (adenopathy, lymphangioleiomyomas). Serum vascular endothelial growth factor-D (VEGF-D), a lymphangiogenic factor, has been recently considered as a novel marker for LAM. Herein we report the diagnostic and differential diagnostic value of serum VEGF-D in LAM patients and evaluate the change of serum VEGF-D levels before and after treatment with sirolimus. The study group included 66 patients with LAM (47 definite LAM and 19 probable LAM based on European Respiratory Society guidelines), 14 patients with other polycystic lung diseases, and 20 healthy female controls. Serum VEGF-D levels were quantified by enzyme-linked immunoassay (ELISA). Serum VEGF-D levels were significantly increased in definite LAM patients compared with healthy controls (3890.3±373.3 pg/ml vs. 413.3±33.2 pg/ml, p<0.05). The optimal cutoff point for LAM diagnosis was 692.5 pg/ml with sensitivity of 97.9% and specificity of 100%. In probable LAM patients, serum VEGF-D levels were all greater than 692.5 pg/ml. Serum VEGF-D levels were significantly increased in definite LAM patients who had chylothorax compared with those without chylothorax (5153.9±598.3 pg/ml vs. 2869.8±372.8 pg/ml, p<0.05). But serum VEGF-D levels in LAM patients with/without pneumothorax, AML, and lymphangioleiomyomas were not significantly changed. Serum VEGF-D levels in definite LAM patients and patients with other cystic lung diseases were 3890.3±373.3 pg/ml and 412.6±27.5 pg/ml, respectively (p <0.05). We determined an optimal cutoff value of 688.5pg/ml, resulting in sensitivity of 97.9% and specificity of 100%. Following a median of 12-month treatment with sirolimus, serum VEGF-D levels decreased from 3135.0±909.4 pg/ml to 1731.8±621.2 pg/ml and symptoms improved. Our study found that serum VEGF-D levels were significantly higher in LAM patients compared with healthy controls and patients with other polycystic lung diseases and that the levels were further increased when complicated by chylothorax. Serum VEGF-D levels may be useful for diagnosis and differential diagnosis with high specificity and sensitivity as well as for following treatment response with sirolimus.

The effects of rosiglitazone on atherosclerotic progression in patients with Type 2 diabetes at high cardiovascular risk.

AIMS: Cardiovascular mortality remains high despite intensive treatment of people with Type 2 diabetes mellitus. Meta-analyses on rosiglitazone have raised concerns regarding its cardiovascular safety. We studied the effects of rosiglitazone on ultrasonic indices of carotid arterial disease and inflammatory markers in a group of Type 2 diabetic patients at high cardiovascular risk. METHODS: A trial of rosiglitazone in Type 2 diabetic patients with high cardiovascular risk and internal carotid artery plaque compared changes in carotid ultrasound intima-media thickness (IMT), plaque thickness, arterial stiffness and compliance, and inflammatory markers at baseline, 26 and 52 weeks. RESULTS: In the rosiglitazone group (n=28), carotid artery plaque thickness was reduced by 0.08 mm, compared with an increase of 0.19 mm (P=0.075) in the placebo group (n=29). There were no significant differences in changes of IMT, carotid wall compliance and stiffness between the two groups. Glycated haemoglobin reduced by -0.9 vs. 0.1% (-7 vs. 2 mmol/mol), (P<0.001); insulin resistance (HOMA-IR) reduced by -37.6 vs. -1.1% (P=0.016); and B cell function (HOMA-B) increased by 36.8 vs. 0.7% (P=0.009). Non-esterified fatty acids reduced by -23.5 vs. 7.9% (P=0.005); tissue plasminogen activator reduced by -25.0 vs. 0.6% (P=0.001); and plasminogen activator inhibitor activity reduced by -57.4 vs. -34.6% (P=0.052). CONCLUSIONS: Rosiglitazone reduced carotid artery plaque thickness, though not significantly, and there was no significant change in intima media thickness or other ultrasonic indices of carotid arterial disease. There were significant improvements in glycaemic control, insulin sensitivity and fibrinolytic, but not inflammatory, markers. There was no evidence in this study of any adverse effects on progression of carotid arterial disease.