Open Access

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/m2; hemoglobin A1c [HbAlc] 7.6 ± 1.1%) with (1) insufficient glycemic control under a dose of metformin >1700 mg/day and/or metformin plus additional oral antidiabetes drugs (OADs) and (2) appropriate residual ?-cell function. Initially, an inpatient 34 h continuous intravenous insulin infusion was performed, and metformin was given (2? 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.

BACKGROUND Type 2 diabetes mellitus (T2DM) is characterized by a proinflammatory and procoagulant condition. This study investigates the impact of a pioglitazone plus metformin therapy on biomarkers of inflammation and platelet activation in comparison to a treatment with glimepiride plus metformin. METHODS The study was designed as a multicenter, randomized, double-blinded two-arm trial. Patients with T2DM and dyslipidemia under metformin monotherapy with hemoglobin A1c value between 6.5% and 9.0% were eligible for trial participation. Blood was drawn at baseline and after 24 weeks of treatment from patients of five centers. Markers of inflammation and thrombocyte function (soluble CD40 ligand, thromboxane, vWillebrand factor, adhesion molecules, clotting reaction) were evaluated subsequently in a central laboratory. RESULTS A total of 46 patients were included in the final analyses. Mean (± standard deviation) age was 58.5 ± 9.0 years (13 women, 33 men; disease duration 6.3 ± 5.0 years; body mass index 32.0 ± 4.8 kg/m(2)). A total of 25 patients were treated with pioglitazone plus metformin, and 21 patients were in the glimepiride arm. There was a significant decline of E-selectin (-3.7 ± 4.8 ng/ml, p < .001 versus baseline), vWillebrand factor (-19.5 ± 32.0%, p < .05), and high-sensitivity C-reactive protein concentrations (-1.08 ± 0.91 mg/liter, p < .05) in the metformin + pioglitazone arm only (metformin + glimepiride, -0.5 ± 3.4 ng/ml, +1.4 ± 33.2%, + 0.08 ± 0.72 mg/liter, respectively, all not significant). Also, all other surrogate markers for platelet function and inflammation showed slight improvements in the metformin + pioglitazone arm but not in the metformin + glimepiride arm. CONCLUSIONS The fixed metformin + pioglitazone combination treatment showed an overall improvement of laboratory surrogate markers, indicating improvement of platelet function and of chronic systemic inflammation, which was not seen with metformin + glimepiride.

Background:Anecdotal reports from pediatric sites have indicated that some blood glucose meters may display wrong and misleading numbers rather than error indications, when operated in deviation from the instructions for use (IFU), eg by manipulating the strip during the count-down phase.Methods:This study was performed with 60 patients with diabetes (32 female, 28 male, 21 type 1, 39 type 2, age (mean±SD): 56±11 years) who measured their blood glucose levels twice with five different blood glucose meters (Precision? Xceed? [Abbott Medisense], Freestyle Mini? [Abbott Medisense], Accu-Chek? Comfort [Roche Diagnostics], Accu-Chek? Aviva [Roche Diagnostics], and Ascensia Contour? [Bayer Vital]). The first measurement was performed in accordance with the IFU, and the second by manipulating the test strip using a standardised inflexion/release procedure during the count-down phase. A standard glucose oxidase method (SuperGL) served as laboratory reference.Results:All meters worked in full compliance with current accuracy standards when operated according to the IFU. When manipulating the test strip, the results varied considerably: While changes in reliability were acceptable for two devices (Precision? Xceed?, Freestyle Mini?), the other devices produced an unacceptable number of errors and a series of entirely wrong values without error indication.Conclusions:The use of all devices is recommended when used according to the IFU. The use under the artificially induced impaired testing conditions is a major concern. This study underlines the importance of appropriate patient training regarding adherence to the IFU of glucose meters.

This study was performed to evaluate the role of protein kinase C (PKC) activity in the development of chemoresistance in clinical breast cancer cells. To simulate the clinical situation, native tumor cells derived from 10 patients with advanced breast cancer were brought into short-term cultures, and treated with anthracyclines (doxorubicin, mitoxantrone), paclitaxel and combinations, respectively. After 3 days of incubation, we determined total PKC activity relative to each control incubated with blank medium.

Although p27 plays a central role in cell cycle regulation, its role in breast cancer prognosis is controversial. Furthermore, the p27 gene CDKN1B carries a polymorphism with unknown functional relevance. This study was designed to evaluate p27 expression and p27 genotyping with respect to early breast cancer prognosis. 279 patients with infiltrating metastasis-free breast cancer were included in this study. p27 expression was determined in tumor tissue specimens from 261 patients by immunohistochemistry. From 108 patients, the CDKN1B genotype was examined by PCR and subsequent direct sequencing. 55.2% of the tumors were considered p27 positive. p27 expression did not correlate with any of the established parameters except for nodal involvement but significantly correlated to prolonged disease-free survival. In 35% of the tumors analyzed, the CDKN1B gene showed a polymorphism at codon 109 (V109G). The V109G polymorphism correlated with greater nodal involvement. In the node-negative subgroup, V109G correlated significantly with a shortened disease-free survival. In conclusion, the determination of the CDKN1B genotype might be a powerful tool for the prognosis of patients with early breast cancer.