title: 3.5 years of insulin therapy with insulin glargine improves in vivo endothelial function in type 2 diabetes.
abstract: OBJECTIVE
  To determine long-term effects of insulin glargine on vascular function in patients with type 2 diabetes.
  
  
  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.
authors.affiliation: Department of Medicine, Division of Diabetes, University of Helsinki,Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Vehkavaara
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D001823:Body Composition / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008055:Lipids / Q000097:blood; D008297:Male; D016555:Matched-Pair Analysis; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D015203:Reproducibility of Results; D013995:Time; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D049528:Insulin, Long-Acting; D008055:Lipids; D009599:Nitroprusside; D000069036:Insulin Glargine; D008687:Metformin; D000109:Acetylcholine