Circulating angiopoietin-2 and soluble Tie-2 in type 2 diabetes mellitus: a cross-sectional study

BACKGROUND: Type 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. METHODS: In 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%). RESULTS: After 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 (HbA(1c)), 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 HbA(1c), 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. CONCLUSIONS: Ang-2 is independently associated with levels of GGT while sTie-2 is independently associated with levels of HbA(1c), 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.