Combined pioglitazone and metformin treatment maintains the beneficial effect of short-term insulin infusion in patients with type 2 diabetes: results from a pilot study.

BACKGROUND: The aim of our study was to examine the efficacy of short-term intravenous insulin intervention followed by oral pioglitazone/metformin therapy to prevent patients from continuous insulin application. METHODS: This prospective, open-label, 4-month pilot study comprised of 14 diabetes patients (5 female, 9 male; age 60 +/- 2 years; body mass index 29 +/- 3.2 kg/m(2); hemoglobin A1c [HbA1c] 7.6 +/- 1.1%) with (1) insufficient glycemic control under a dose of metformin >or=1700 mg/day and/or metformin plus additional oral antidiabetes drugs (OADs) and (2) appropriate residual beta-cell function. Initially, an inpatient 34 h continuous intravenous insulin infusion was performed, and metformin was given (2x 850 mg/day). Insulin was stopped, and pioglitazone 30 mg/day was added at the second inpatient day. Patients were followed for four months. Efficacy parameters [change of HbA1c, fasting blood glucose [FBG], intact proinsulin, adiponectin, and high-sensitivity C-reactive protein (hsCRP)] were assessed after initial normalization of blood glucose values by intravenous insulin and at the study end point. RESULTS: During the acute insulin intervention, FBG levels were stabilized in all study subjects. In the following OAD treatment period, five patients showed an improvement of HbA1c > 0.5% [35.7%; seven patients remained stable (50.0%), two patients were nonresponders (14.3%)]. Fasting glucose values dropped after insulin infusion (-17.7%; p < .001). This effect was maintained during the consecutive OAD treatment period (glucose +0.3%, not significant (NS); HbA1c -6.0%; p < .05). The initial decrease in fasting intact proinsulin levels was also maintained during the study (end value -41%, p < .05). Improvements in hsCRP values (postinsulin value, -15%, NS; end value -37%; p < .05) and adiponectin values (postinsulin value +15%, NS; end value +128%; p < .001) were demonstrated at end point only after continued glitazone intake. CONCLUSIONS: Our pilot study demonstrated that a beneficial effect of a short-term intravenous insulin application on glycemic control was effectively maintained by pioglitazone/metformin treatment for at least 4 months. In addition, the oral therapy significantly improved cardiovascular risk parameters.

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.