Pioglitazone in addition to metformin improves erythrocyte deformability in patients with Type 2 diabetes mellitus.

The aim of the present study was to compare the effect of PIO (pioglitazone) or GLIM (glimepiride) on erythrocyte deformability in T2DM (Type 2 diabetes mellitus). The study covered 23 metformin-treated T2DM patients with an HbA1c (glycated haemoglobin) >6.5%. Patients were randomized to receive either PIO (15 mg, twice a day) or GLIM (1 mg, twice a day) in combination with metformin (850 mg, twice a day) for 6 months. Blood samples were taken for the measurement of fasting glucose, HbA1c, fasting insulin, intact proinsulin, adiponectin and Hct (haematocrit). In addition, the erythrocyte EI (elongation index) was measured using laser diffractoscopy. Both treatments significantly improved HbA1c levels (PIO, -0.9+/-1.1%; GLIM, -0.6+/-0.4%; both P<0.05) and resulted in comparable HbA1c levels after 6 months (PIO, 6.5+/-1.2%; GLIM, 6.2+/-0.4%) Treatment with PIO reduced fasting insulin levels (-8.7+/-15.8 milli-units/l; P=0.098), intact proinsulin levels (-11.8+/-9.5 pmol/l; P<0.05) and Hct (-1.3+/-2.3%; P=0.09), whereas adiponectin levels increased (8.2+/-4.9 microg/ml; P<0.05). No significant change in these parameters was observed during GLIM treatment. PIO improved the EI, resulting in a significant increase in EI at all physiological shear stress ranges (0.6-6.0 Pa; P<0.05). The improvement in EI correlated with the increase in adiponectin levels (r=0.74; P<0.001), and inversely with intact proinsulin levels (r=-0.47; P<0.05). This is the first study showing an improvement in EI during treatment with PIO, which was associated with an increase in adiponectin and a decrease in intact proinsulin levels, but independent of glycaemic control.

Increased arterial augmentation and augmentation index as surrogate parameters for arteriosclerosis in subjects with diabetes mellitus and nondiabetic subjects with cardiovascular disease.

BACKGROUND: Arterial augmentation (AP) and the augmentation index (Aix) are surrogate parameters of arterial stiffness and are commonly used as predictors for cardiovascular risk. The aim of this study is to compare these parameters in diabetic subjects and nondiabetic cardiovascular risk subjects with healthy control subjects. METHODS: One hundred sixty-six nonsmoking subjects aged between 35 and 70 years were included in the study, which included 100 subjects with cardiovascular disease but not diabetes (mean age 62.73+/-8.75 years), 33 subjects with type 2 diabetes (66.58+/-2.69 years), and 33 healthy controls (51.89+/-8.91 years). In these subjects, arterial stiffness was measured by the difference between the second and the first systolic peak of the central pressure waveform, and the Aix was calculated as the percentage of Aix from pulse pressure. RESULTS: Arterial augmentation was increased in subjects with diabetes (DM) with 10.21+/-6.97 mm Hg and in subjects with cardiovascular disease but not diabetes (CV) with 10.74+/-5.29 mm Hg in comparison to healthy controls (C) with 6.59+/-3.97 mm Hg (p < 0.0005 DM vs C; p < 0.00005 CV vs C). Moreover, Aix was increased with 26.00+/-9.91% in CV subjects compared to healthy controls with 19.84+/-9.37% (p < 0.02 CV vs C). The augmentation index was increased with 21.12+/-11.21% in subjects with type 2 diabetes mellitus compared to controls, but failed to be statistically significant. There was no statistical significance in arterial augmentation or the augmentation index between CV and diabetic subjects. CONCLUSION: The results of our study revealed a comparable increased augmentation index as a surrogate measure of arterial stiffness and arteriosclerosis in subjects with diabetes mellitus and in nondiabetic subjects with cardiovascular disease.

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.

Efecto de la fenitoína prenatal en fetos de rata: estudio morfológico y morfométrico de la glándula submandibular / Effect of prenatal phenytoin on rat fetuses: and morphometrical study of the submandibular gland

La fenitoína (difenil hidantoína) es una droga anticonvulsiva y antiarrítmica, que posee acción teratógena en animales y humanos, causando importantes alteraciones, aún cuando se administra en dosis no teratógenas. Con el objetivo de estudiar morfológica y morfométricamente los efectos de la droga sobre la glándula submandibular fetal, ratas Wistar fueron inyectadas el 10ª día de preñez, con 70, 100 ó 150 mg/kg de fenitoína. Las dosis más altas provocaron la muerte intrauterina de todos los fetos. El peso de los fetos de las ratas inyectadas con 70 mg/kg de fenitoína fue menor que el de los controles. El examen histopatológico de la glándulas submandibular reveló una glándula inmadura, constituida por acinos y conductos mayores y con luz disminuida. Las células de los acinos y conductos eran mayores, con núcleos más grandes. El tejido conjuntivo era más escaso en los fetos del grupo tratado. Morfométricamente, fue posible confirmar los hallazgos histopatológicos. Los resultados sugieren que la exposición prenatal a la fenitoína, en dosis no teratógenas, actúa en la embriogénesis, causando alteraciones en el desarrollo (menor peso, cordón umbilical más corto y glándula submandibular menos diferenciada), mostrando el feto tratado aspectos de inmaturidad