The Role of Insulin on Function of Resistance Arteries from Obese Young Women at Risk of ‘Diabetes’ and Controls

Objectives: Vascular dysfunction is common in type 2 diabetes and obesity. The functional role of hyperinsulinaemia on human blood vessels in obese individuals remains unclear. We hypothesised that in young women, change in vessel function in a hyperinsulinaemic milieu would be influenced more by adiposity than plasma glucose. Methods and Results: Women in a pregnancy cohort were stratified into upper & lower quartiles of fasting plasma glucose (FPG) when seen at follow-up 20 months after delivery. After subcutaneous biopsy, small arteries were tested ex-vivo by wire myography for vasoconstrictor [Noradrenaline (NA)] and vasodilator [carbachol and sodium nitroprusside (SNP)] responses before and after incubation with 100 mU/ml human insulin. Results: Women with higher FPG had attenuated NA-contractile responses [0.8 (0.4–1.39) vs. 0.6 (−0.5 to 1.7) mN/mm, p=0.011), but differences in maximum response to carbachol (ΔEDDmax) before and after insulin incubation did not increase [26.8 (4.8–48.7) vs. 18.5 (−3.3 to 30.2) %, p=0.55) compared with those with lower FPG. Insulin reduced NA-induced contraction in those with higher [3.5 (2.4–4.6) vs. 2.4 (1.4–3.4) mN/mm: p=0.004] but not in those with lower BMI [4.1 (2.8–5.3) vs. 3.7 (2.5–5.0) mN/mm: p=0.33]. ΔEDDmax was greater in the high than low BMI group [37.7 (18.0 to 57.3) % vs.6.3 (−6.5 to 19.1) %, p=0.007]. Conclusions: Small arteries from women with greater adiposity and fasting glucose, exhibited reduced contraction with NA but only the former showed improved EDD, when tested in a hyperinsulinaemic milieu. Hyperinsulinaemia may be important in maintaining endothelial function in obesity.