Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease

Objective： Type 2 diabetes coexistent with lower extremity artery disease （peripheral arterial disease （PAD）） can be observed in numerous patients. The mechanism compensating for ischemia and contributing to healing is angiogenesis-the process of forming new blood vessels. The purpose of this study was to assess the likely impact of type 2 diabetes on the plasma levels of proangiogenic factor （vascular endothelial growth factor A （VEGF-A）） and angiogenesis inhibitors （soluble VEGF receptors type 1 and type 2 （sVEGFR-1 and sVEGFR-2）） in patients with PAD. Methods： Among 46 patients with PAD under pharmacological therapy （non-invasive）, we identified, based on medical history, a subgroup with coexistent type 2 diabetes （PAD-DM2＋, n=15） and without diabetes （PAD-DM2-, n=31）. The control group consisted of 30 healthy subjects. Plasma levels of VEGF-A, sVEGFR-1, and sVEGFR-2 were measured using the enzyme-linked immunosorbent assay （ELISA） method. Results： The subgroups of PAD-DM2＋ and PAD-DM2- revealed significantly higher concentrations of VEGF-A （P=-0.000007 and P=0.0000001, respectively） and significantly lower sVEGFR-2 levels （P=-0.02 and P=-0.00001, respectively）, when compared with the control group. Patients with PAD and coexistent diabetes tended to have a lower level of VEGF-A and higher levels of sVEGFR-1 and sVEGFR-2 comparable with non-diabetic patients. Conclusions： The coexistence of type 2 diabetes and PAD is demonstrated by a tendency to a lower plasma level of proangiogenic factor （VEGF-A） and higher levels of anglogenesis inhibitors （sVEGFR-1 and sVEGFR-2） at the same time. Regardless of the coexistence of type 2 diabetes, hypoxia appears to be a crucial factor stimulating the processes of angiogenesis in PAD patients comparable with healthy individuals, whereas hyperglycemia may have a negative impact on angiogenesis in lower limbs.

Overweight and obesity versus concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 in plasma of patients with lower limb chronic ischemia

Objective： Being overweight or obese comprises a significant risk factor for atherosclerosis. Fat tissue also generates factors stimulating angiogenesis, the process by which new blood vessels form. The purpose of this paper is to assess concentrations of the vascular endothelial growth factor A （VEGF-A） and its soluble type-1 and type-2 re- ceptors （sVEGFR-1 and sVEGFR-2） in plasma of patients with peripheral arterial disease （PAD） depending on the level of nutrition according to body mass index （BMI）. Methods： The study group included patients suffering from symptomatic PAD （n=46） in Fontaine classes Ila-lV without any history of neoplastic disease and who have a normal BMI （n=15）, are overweight （n=21） or are obese （n=10）. The control group （n=30） consisted of healthy non-smoking volunteers who were neither overweight nor obese. Venous blood plasma samples were collected from both groups at rest in the morning to determine plasma concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 using the enzyme- linked immunosorbent assay （ELISA） method. Results： The group of patients with PAD co-existent with being over- weight or obese tended to have higher mean concentration levels of VEGF-A and sVEGFR-2 when compared with patients suffering from PAD with normal BMIo A statistically significant positive correlation was obtained between BMI and average plasma concentrations of sVEGFR-2 （R=0.37, P=-0.0103）. However, no significant correlation was no- ticed between BMI and VEGF-A or sVEGFR-1 concentrations. Conclusions： A positive correlation determined be- tween the level of antiangiogenic factor and BMI value may be indicative of the linearly growing prevalence of some antiangiogenic factors in patients with metabolic disorders, which may be one of numerous factors contributing to incomplete efficiency of collateral circulation development in patients with PAD.

CRP, but not TNF-α or IL-6, decreases after weight loss in patients with morbid obesity exposed to intensive weight reduction and balneological treatment

Objective：The aim of this study was to evaluate the concentrations of C-reactive protein （CRP）, tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6）, and the degree of homeostasis model assessment-insulin resistance （HOMA-IR） in patients with morbid obesity exposed to a three-week low-calorie diet and balneotherapy. Methods：The study included 33 patients （25 females and 8 males; mean age 46 years） with body mass index （BMI） values of〉40 kg/m2. Evaluations of CRP, IL-6, TNF-α, lipid profile, HOMA-IR, and fasting glucose were carried out before （baseline data） and three weeks after the treatment. The control group consisted of 20 healthy volunteers （15 females and 5 males） with a mean age of 39 years and BMI values of≤24.9 kg/m2. Results：In the blood of patients with morbid obesity we found significantly elevated levels of CRP, TNF-α, triglycerides, HOMA-IR and fasting glucose, but a de-creased level of high density lipoprotein （HDL）-cholesterol, compared with the healthy individuals. The treatment resulted in about a 9.4%reduction in body weight from 122.5 to 111.0 kg and a significant decrease in the concen-tration of CRP, but no change in TNF-αor IL-6. HOMA-IR was significantly reduced. Conclusions：The decrease in CRP level without changes in TNF-α or IL-6 concentrations after the low-calorie diet and balneological treatment, suggests that an essential amount of adipose tissue must be removed before proper adipocyte function is restored. The decrease in HOMA-IR indicates an improvement in insulin sensitivity, which is beneficial in obese patients.