A total of 75 in vivo endothelial function tests (intrabrachial artery infu
sions of endothelium-dependent [acetylcholine] and -independent [sodium nit
roprusside] vasoactive agents) were performed in 18 type 2 diabetic patient
s (aged 58+/-2 years, body mass index 28.5+/-0.6 kg/m(2), and fasting plasm
a glucose 229+/-11 mg/dL) and 27 matched normal subjects. These tests were
performed before and 6 months after combination therapy with insulin and me
tformin and before and 6 months after metformin therapy only. Before insuli
n therapy, blood flow responses to acetylcholine (15 mu g/min) were signifi
cantly blunted in type 2 diabetic patients (7.5+/-0.7 mL . dL(-1) . min(-1)
) compared with normal subjects (11.6+/-0.9 mL . dL(-1) . min(-1), P<0.01).
During insulin therapy, the acetylcholine response increased by 44% to 10.
8+/-1.6 mL . dL(-1) . min(-1) (P<0.05). Insulin therapy also significantly
increased the blood flow responses to both low and high doses of sodium nit
roprusside. We conclude that insulin therapy improves endothelium-dependent
and -independent vasodilatation. These data support the idea that insulin
therapy has beneficial rather than harmful effects on vascular function.