3.5 Years of Insulin Therapy With Insulin Glargine Improves In Vivo Endothelial Function in Type 2 Diabetes

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 24; no. 2; pp. 325 - 330
• Main Authors: Vehkavaara, Satu, Yki-Järvinen, Hannele
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-02-2004; Hagerstown, MD Lippincott
• Subjects: Acetylcholine - pharmacology; Adult; Aged; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood Flow Velocity - drug effects; Blood Glucose - drug effects; Blood Glucose - physiology; Body Composition - drug effects; Body Composition - physiology; Cardiology. Vascular system; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug Administration Schedule; Drug Therapy, Combination; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Female; Humans; Insulin - analogs & derivatives; Insulin - therapeutic use; Insulin Glargine; Insulin, Long-Acting; Lipids - blood; Male; Matched-Pair Analysis; Medical sciences; Metformin - therapeutic use; Middle Aged; Nitroprusside - pharmacology; Reproducibility of Results; Time; Vasodilation - drug effects; Vasodilation - physiology; Vascular disease; Type 2 diabetes; Hyperglycemia; Insulin glargine; Treatment; Atherosclerosis; circulation; blood vessels; Cardiovascular disease; insulin therapy
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000113817.48983.c5

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 (age59±2 years; BMI29.7±0.9 kg/m; fasting plasma glucose226±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 months7.7±0.5; at 6 months9.9±0.6; P <0.01 for 6 versus 0 months; and 3.5 years11.6±1.1 mL/dL per minute; P <0.02 for 3.5 years versus 0 months) and high (blood flow at 0 months10.7±0.9; 6 months13.4±1.0; P <0.05 for 6 versus 0 months; and 3.5 years16.6±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.