Efficacy and tolerability of vildagliptin as an add-on to glimepiride in Japanese patients with Type 2 diabetes mellitus.

AIM: To investigate the efficacy and tolerability of vildagliptin, a potent and selective dipeptidyl peptidase-4 inhibitor, as add-on to glimepiride in Japanese patients with Type 2 diabetes mellitus (T2DM) who were inadequately controlled. METHODS: This 12-week, randomized, double-blind, placebo-controlled study compared vildagliptin 50mg twice-daily (n=102) with placebo (n=100) when added to a stable dose of glimepiride (>or=1mg/d). RESULTS: Treatment groups were balanced at baseline (glycosylated hemoglobin [HbA(1c)], 7.9%; fasting plasma glucose, 163.8 mg/dL). During treatment HbA(1c) decreased progressively with vildagliptin, but remained unchanged with placebo. The adjusted mean change (AMDelta) at endpoint was -1.0+/-0.1 and -0.1+/-0.1% in vildagliptin- and placebo-treated patients (between-group Delta=-1.0+/-0.1%, P<0.001). A greater proportion of vildagliptin-treated patients had HbA(1c)

Management of type 2 diabetes in treatment-naive elderly patients: benefits and risks of vildagliptin monotherapy.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of vildagliptin in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Efficacy data from five double-blind, randomized, placebo- or active-controlled trials of >or=24 weeks' duration were pooled. Effects of 24-week vildagliptin monotherapy (100 mg daily) were compared in younger (<65 years, n = 1,231) and older (>or=65 years, n = 238) patients. Safety data from eight controlled clinical trials of >or=12-weeks' duration were pooled; adverse event profiles in younger (n = 1,890) and older (n = 374) patients were compared. RESULTS: Mean baseline A1C and fasting plasma glucose (FPG) were significantly lower in older (70 years: 8.3 +/- 0.1% and 9.6 +/- 0.1 mmol/l, respectively) than in younger (50 years: 8.7 +/- 0.0% and 10.5 +/- 0.1 mmol/l, respectively) patients. Despite this, the adjusted mean change from baseline (AMDelta) in A1C was -1.2 +/- 0.1% in older and -1.0 +/- 0.0% in younger vildagliptin-treated patients (P = 0.092), and the AMDelta in FPG was significantly larger in older (-1.5 +/- 0.2 mmol/l) than in younger (-1.1 +/- 0.1 mmol/l, P = 0.035) patients. Body weight was significantly lower at baseline in older (83.4 +/- 1.0 kg) than in younger (92.0 +/- 0.6 kg) patients. Weight decreased significantly in the older subgroup (AMDelta -0.9 +/- 0.3 kg, P = 0.007), whereas smaller, nonsignificant decreases occurred in younger patients (AMDelta -0.2 +/- 0.1 kg). Adverse event rates were slightly higher in older than in younger subgroups but were lower among older, vildagliptin-treated subjects (63.6%) than in the pooled active comparator group (68.1%). Vildagliptin treatment did not increase adverse events among older patients with mild renal impairment (62.0%). Hypoglycemia was rare (0.8%) in the elderly patients, and no severe events occurred. CONCLUSIONS: Vildagliptin monotherapy was effective and well tolerated in treatment-naive elderly patients.

Effect of chronic exercise and Angiotensin-converting enzyme inhibition on rodent thoracic aorta.

Vascular reactivity can be modulated by local physical factors as well as pharmacologic manipulations. The aim of this study was to evaluate the effects of chronic exercise (EX) with or without the ACEI captopril (CAP) on vascular reactivity. Sixty-four Sprague-Dawley male rats were randomized into 4 groups (n = 16): group 1, control; group 2, captopril; group 3, exercise; and group 4, exercise and captopril. After 10 weeks of treatment, rats were killed, and their thoracic aortas harvested. Vascular reactivity was studied in an organ chamber (n = 12). Aortic endothelium constitutive nitric oxyde synthase (NOS3) expression was determined by Western blot analysis (n = 4). Endothelial-dependent relaxation was increased in both CAP and EX rats relative to the control group. Maximal aortic relaxations were enhanced in the CAP group, and potencies of these mediators were enhanced in the EX group (P < 0.05 versus control). Combined treatment did not result in a synergistic effect. NOS3 relative expressions were: group 1, 100%; group 2, 241%; group 3, 64%; and group 4, 108%. Exercise enhanced both potencies and efficacies of the mediators studied, whereas CAP increased mainly their efficacies. NOS3 protein expression was up-regulated in CAP-treated rats but not in exercised rats. These findings suggest different mechanisms for the observed increased vascular reactivity.

Detection of myocardial perfusion abnormalities after a recent acute coronary syndrome by quantitative Levovist myocardial contrast echocardiography: comparison with 99m Tc-Myoview SPECT imaging.

BACKGROUND: The value of stress harmonic power Doppler imaging (HPDI) for the evaluation of myocardial perfusion has never been assessed in patients after acute coronary syndrome (ACS). OBJECTIVE: To evaluate the agreement between stress HPDI and single photon emission computed tomography (SPECT) imaging for the assessment of myocardial perfusion after unstable angina or myocardial infarction. PATIENTS AND METHODS: Thirty patients with a recent ACS underwent HPDI and SPECT. Images were obtained at rest and during dipyridamole infusion (0.56 mg/kg over 4 min). Apical two- and four-chamber views were used for HPDI. Ten myocardial segments were scored for myocardial perfusion. Semiquantitative and quantitative video intensity analysis with background subtraction were performed. RESULTS: Concordance by patients between quantitative HPDI and SPECT was 76% (kappa=0.40, Phi=0.46) for normal versus abnormal perfusion. When semiquantitative analysis was used, concordance was 72% (kappa=0.42, Phi=0.46). Agreement between methods was best in the left anterior descending artery territory for quantitative (80%) (kappa=0.60, Phi=0.60) and semiquantitative analysis (78%) (kappa=0.51, Phi=0.60) for normal versus abnormal perfusion. Discrepancies between HPDI and SPECT were most important in the circumflex territory, with a concordance of 59% (kappa=0.22) for identification of normal perfusion versus irreversible and reversible defects. CONCLUSIONS: These results suggest that HPDI can detect myocardial perfusion at rest and during pharmacological stress in patients after a recent ACS. Given the suboptimal agreement with SPECT, further advances are required before the routine use of contrast echocardiography is possible for the assessment of myocardial perfusion.

Prediction trees with soft nodes for binary outcomes.

Consider the problem of predicting the occurrence of an event, the onset of diabetes mellitus, say, from a vector of continuous and discrete predictors. We propose a new algorithm for the construction of a tree-structured predictor for the event of interest, which uses a new approach for dealing with continuous predictors. The novelty is that the tree uses splits for continuous variables. This means that at each node an individual goes to the right branch with a certain probability, function of a predictor. The predictor as well as the particular shape of the function is chosen from the data by the proposed algorithm. We evaluate its performance on several real data sets, in particular comparing it with a standard tree-growing algorithm. We also present an analysis of a well-known data set, the Pima Indian diabetes data set, to illustrate the application of the method in biostatistics.

Effects of plaque composition on vascular remodelling after angioplasty in the MultiVitamins and Probucol (MVP) trial.

BACKGROUND: The antioxidant probucol reduced coronary restenosis in the MultiVitamins and Probucol (MVP) trial by improving vascular remodelling. Whether calcification limits the extent of adaptive vessel enlargement is not known. OBJECTIVE: To determine whether plaque composition at the dilated site affects probucol-induced vascular remodelling after angioplasty. PATIENTS AND METHODS: Beginning 30 days before percutaneous transluminal coronary angioplasty (PTCA), 317 patients received either probucol, vitamins, probucol and vitamins, or placebo. Patients were then treated for six months after PTCA. Intravascular ultrasound (IVUS) was performed post-PTCA and at follow-up in 94 patients (111 segments). The cross-section for serial analysis was the one at the angioplasty site with the smallest lumen area at follow-up. Quantitative analysis consisted of measurements of lumen area and external elastic membrane (EEM) area. The selected cross-section was also divided into five regions according to the type of plaque present (calcific, fibrotic, hypoechoic, fibrohypoechoic or normal). Plaque characterization scores (PCS) (PCS for arc, area, inner perimeter and outer perimeter) were calculated using weighting factors. RESULTS: There were no interactions between potential PCS covariates and probucol main effect on changes in lumenal, EEM and wall area. There were no significant PCS covariates in the model for change in EEM as they were all removed using a backward stepwise procedure. The last potential covariate (area PCS) had a significance level of P=0.48. In contrast, probucol significantly influenced the change in EEM over time (P=0.003). CONCLUSION: Plaque composition at the dilated site does not appear to influence probucol-induced vascular remodelling after angioplasty.