on December 18, 2003
Published online before print December 18, 2003, doi: 10.1161/01.ATV.0000113817.48983.c5
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Submitted on October 12, 2003
Accepted on November 27, 2003
3.5 Years of Insulin Therapy With Insulin Glargine Improves In Vivo Endothelial Function in Type 2 Diabetes
Satu Vehkavaara and Hannele Yki-Järvinen *
From the Department of Medicine, Division of Diabetes, University of Helsinki, Finland.
* To whom correspondence should be addressed. E-mail: ykijarvi{at}helsinki.fi.
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.
Key words: hyperglycemia • circulation • blood vessels • insulin therapy
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