3.5 years of insulin therapy with insulin glargine improves in vivo endothelial function in type 2 diabetes.

OBJECTIVE To determine long-term effects of insulin glargine on vascular function in patients with type 2 diabetes. METHODS AND RESULTS A total of 49 in vivo endothelial function tests, intrabrachial artery infusions of endothelium-dependent (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside [SNP]) vasoactive agents, were performed in 11 patients with type 2 diabetes (age: 59+/-2 years; BMI: 29.7+/-0.9 kg/m2; fasting plasma glucose: 226+/-14 mg/dL) and 16 matched normal subjects. The tests in the type 2 diabetic patients were performed before and after 6 months and 3.5 years of combination therapy with insulin glargine and metformin. A control group of type 2 diabetic patients not treated with insulin was studied twice at 6-month intervals. Before treatment, blood flow during infusions of low and high doses of ACh were significantly lower in the type 2 diabetic patients than in the normal subjects (P=0.021 for ANOVA). In the patients with type 2 diabetes, blood flow during infusion of the low dose of ACh averaged 7.1+/-0.8 mL/dL per minute at baseline, 8.8+/-1.0 mL/dL per minute at 6 months (NS), and then increased compared with baseline by 87+/-29% to 11.6+/-1.4 mL/dL per minute at 3.5 years (P<0.02 versus baseline). Blood flow during infusion of the high dose of ACh increased from 8.8+/-0.9 at baseline to 13.0+/-1.9 mL/dL per minute at 6 months (P<0.05) and by 86+/-25% to 14.7+/-1.6 mL/dL per minute at 3.5 years (P<0.01 versus baseline), which was not different from normal subjects. Blood flow during infusion of low (blood flow at 0 months: 7.7+/-0.5; at 6 months: 9.9+/-0.6; P<0.01 for 6 versus 0 months; and 3.5 years: 11.6+/-1.1 mL/dL per minute; P<0.02 for 3.5 years versus 0 months) and high (blood flow at 0 months: 10.7+/-0.9; 6 months: 13.4+/-1.0; P<0.05 for 6 versus 0 months; and 3.5 years: 16.6+/-1.5 mL/dL per minute; P<0.05 for 3.5 years versus 0 months) doses of SNP also increased significantly during insulin therapy. CONCLUSIONS We conclude that insulin glargine therapy improves endothelium-dependent and endothelium-independent vasodilatation. These data support the idea that long-term insulin therapy has beneficial rather than harmful effects on vascular function in type 2 diabetes.