Effects of Diabetes and Obesity on Vascular Reactivity, Inflammatory Cytokines, and Growth Factors

Abstract

We examined the influences of obesity and diabetes on endothelium-dependent and -independent vasodilation, inflammatory cytokines, and growth factors. We included 258 subjects, age 21–80 years in four groups matched for age and gender: 40 healthy nonobese (BMI <30 kg·m−2) nondiabetic subjects, 76 nonobese diabetic patients, 37 obese (BMI >30) nondiabetic subjects, and 105 obese (BMI >30) diabetic patients. The flow-mediated dilation (FMD, endothelium-dependent) and nitroglycerin-induced dilation (NID, endothelium-independent) in the brachial artery, the vascular reactivity at the forearm skin and serum growth factors and inflammatory cytokines were measured. FMD was reduced in the nonobese diabetic patients, obese nondiabetic controls, and obese diabetic patients (P < 0.0001). NID was different among all four groups, being highest in the obese nondiabetic subjects and lowest in the obese diabetic patients (P < 0.0001). The resting skin forearm blood flow was reduced in the obese nondiabetic subjects (P < 0.01). Vascular endothelial growth factor (VEGF) was higher in the obese nondiabetic subjects (P < 0.05), tumor necrosis factor–α was higher in the obese diabetic patients (P < 0.0001) and C-reactive protein was higher in both the obese nondiabetic and diabetic subjects (P < 0.0001). Soluble intercellular adhesion molecule-1 was elevated in the two diabetic groups and the obese nondiabetic subjects (P < 0.05). We conclude that diabetes and obesity affect equally the endothelial cell function but the smooth muscle cell function is affected only by diabetes. In addition, the above findings may be related to differences that were observed in the growth factors and inflammatory cytokines.

Association of endothelial proliferation with the magnitude of weight loss during calorie restriction

“…Whilst the concentration of VEGF, a key angiogenic mediator, has been reported to increase in obesity [34], we did not observe its changes following the intervention. Similarly, Cullberg et al [35] did not find significant thrombospondin-1, MMP-9 matrix metalloproteinase-9, bFGF basic fibroblast growth factor Angiogenesis changes in VEGF in serum and adipose tissue in response to diet-induced weight loss.…”

VEGF-A i PDGF-BB — czynniki angiogenne a stopień zaawansowania zespołu stopy cukrzycowej

“…A similar result was obtained by Doupis et al Their research showed increased VEGF level in the serum of non-obese patients with diabetes, and in obese patients with diabetes. However, the highest concentration of VEGF was observed in the group of obese non-diabetics [16].…”

“…However, the concentration of PDGF in the combination AB/BB was elevated in both study groups [26]. Three years later, Doupis et al presented decreased levels of PDGF-AA in the serum of non-obese diabetic patients and obese diabetic patients [16]. Animal studies conducted by Tanii et al demonstrated that in STZ-DM mice (streptozotocin induced diabetes mellitus), PDGF-B gene expression is impaired.…”

Long-Term Effects of Weight Loss and Exercise on Biomarkers Associated with Angiogenesis

“…(23,24) Adipogenesis is dependent upon angiogenesis,(25–27) and VEGF is elevated in the obese state. (28,29) Expansion of fat mass induces hypoxia, a driver of VEGF expression, via HIF-1 stabilization. (30)…”