Abstract
BackgroundType 2 diabetes is associated with increased levels of Angiopoietin-2 (Ang-2) and soluble Tie-2 (sTie-2), but its impact on vascular disease is still unknown. This study aimed to further explore the associations of Ang-2 and sTie-2 with metabolic control and diabetic complications.MethodsIn a cross-sectional designed study, levels of Ang-2 and sTie-2 as well as their relationships to cardiometabolic parameters were determined in 80 type 2 diabetic subjects (age 65 ± 7 years, female 47.4%).ResultsAfter controlling for age and BMI, Ang-2 levels were associated with levels of sTie-2, diastolic blood pressure, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), creatinine, glomerular filtration rate (GFR), and gamma-glutamyl transferase (GGT) (all p < 0.02). Presence of diabetic macrovascular complications, polyneuropathy and insulin therapy were associated with higher Ang-2 levels (p < 0.05). Conversely, sTie-2 levels were associated with glycated hemoglobin (HbA1c), fasting plasma glucose and insulin, HOMA-IR, triglyceride, and liver function parameters (all p < 0.03). Multiple linear regression analysis showed that Ang-2 remained significantly associated only with levels of GGT (p < 0.04), whereas sTie-2 remained significantly associated with HbA1c, insulin levels, and HOMA-IR (p < 0.03). No differences in Ang-2 and sTie-2 levels were observed with regard to gender of participants.ConclusionsAng-2 is independently associated with levels of GGT while sTie-2 is independently associated with levels of HbA1c, plasma insulin and HOMA-IR in type 2 diabetic subjects. Therefore we suggest that the associations of Ang-2 and sTie-2 with type 2 diabetes are based on different patho-physiological mechanisms.
Highlights
Type 2 diabetes is associated with increased levels of Angiopoietin-2 (Ang-2) and soluble tyrosine kinase 2 (Tie-2), but its impact on vascular disease is still unknown
Ang-2 is expressed primarily in the vascular endothelium at sites of vascular remodeling [3]. Both Ang-1 and Ang-2 act by binding to the endothelium-specific receptor tyrosine kinase 2 (Tie-2)
50% presented with diabetic polyneuropathy (50% female), 29.1% with overt diabetic macrovascular complications, 3.8% with microalbuminuria and 3.8% with diabetic retinopathy
Summary
Type 2 diabetes is associated with increased levels of Angiopoietin-2 (Ang-2) and soluble Tie-2 (sTie2), but its impact on vascular disease is still unknown. This study aimed to further explore the associations of Ang-2 and sTie-2 with metabolic control and diabetic complications. Angiopoietins are growth factors that promote angiogenesis together with vascular endothelial growth factor (VEGF). Ang-2 is expressed primarily in the vascular endothelium at sites of vascular remodeling [3]. Both Ang-1 and Ang-2 act by binding to the endothelium-specific receptor tyrosine kinase 2 (Tie-2). A soluble form of the Tie-2 receptor can be detected in human biological fluids [4]. The Ang/Tie system tightly controls the endothelial phenotype during
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