Effect of insulin glulisine on microvascular blood flow and endothelial function in the postprandial state.

OBJECTIVE: To investigate the effect of insulin glulisine on postprandial microvascular blood flow in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 15 patients with type 2 diabetes received insulin glulisine or human insulin before a liquid meal test. Thereafter, skin microvascular blood flow was measured by laser Doppler fluxmetry and blood samples were taken for measurement of plasma levels of glucose, insulin, intact proinsulin, asymmetric dimethylarginine, nitrotyrosine, interleukin-18, matrix metalloproteinase-9, oxidized LDL, and free fatty acids. RESULTS: Insulin glulisine injections resulted in higher postprandial insulin levels (means +/- SEM area under the curve [AUC](0-120) 51.0 +/- 6.8 vs. 38.2 +/- 5.4 mU/l; P = 0.004), while plasma glucose (AUC(0-240) 158 +/- 9 vs. 180 +/- 9 mg/dl; P < 0.05) and intact proinsulin (AUC(0-240) 26.2 +/- 3.5 vs. 31.2 +/- 4.3 pmol/l; P = 0.002) were lower. Microvascular blood flow increased after insulin glulisine injection (27.9 +/- 3.1 to 51.7 +/- 9.9 arbitrary units [AU]; P < 0.05), while only a minor increase was found during human insulin (27.9 +/- 3.1 to 34.4 +/- 7.8 AU; not significant). Asymmetric dimethylarginine and nitrotyrosine levels were reduced after insulin glulisine (P < 0.05). CONCLUSIONS: Insulin glulisine is superior to human insulin in restoring postprandial metabolic and microvascular physiology.

Influence of glucose control and improvement of insulin resistance on microvascular blood flow and endothelial function in patients with diabetes mellitus type 2.

OBJECTIVE: The study was performed to investigate the effect of improving metabolic control with pioglitazone in comparison to glimepiride on microvascular function in patients with diabetes mellitus type 2. METHODS: A total of 179 patients were recruited and randomly assigned to one treatment group. Metabolic control (HbA1c), insulin resistance (HOMA index), and microvascular function (laser Doppler fluxmetry) were observed at baseline and after 3 and 6 months. RESULTS: HbA1c improved in both treatment arms (pioglitazone: 7.52 +/- 0.85% to 6.71 +/- 0.89%, p < .0001; glimepiride: 7.44 +/- 0.89% to 6.83 +/- 0.85%, p < .0001). Insulin-resistance decreased significantly in the pioglitazone group (6.15 +/- 4.05 to 3.85 +/- 1.92, p < .0001) and remained unchanged in the glimepiride group. The microvascular response to heat significantly improved in both treatment groups (pioglitazone 48.5 [15.2; 91.8] to 88.8 [57.6; 124.1] arbitrary units [AU], p < .0001; glimepiride 53.7 [14.1; 91.9] to 87.9 [52.9, 131.0] AU, p < .0001, median [lower and upper quartile]). Endothelial function as measured with the acetylcholine response improved in the pioglitazone group (38.5 [22.2; 68.0] to 60.2 [36.9; 82.8], p = .0427) and remained unchanged in the glimepiride group. CONCLUSIONS: Improving metabolic control has beneficial effects in microvascular function in type 2 diabetic patients. Treatment of type 2 diabetic patients with pioglitazone exerts additional effects on endothelial function beyond metabolic control.