First-line antihypertensive treatment in patients with pre-diabetes: Rationale, design and baseline results of the ADaPT investigation

<p>Abstract</p> <p>Background</p> <p>Recent clinical trials reported conflicting results on the reduction of new-onset diabetes using RAS blocking agents. Therefore the role of these agents in preventing diabetes is still not well defined. Ramipril is an ACE inhibitor (ACEi), that has been shown to reduce cardiovascular events in high risk patients and post-hoc analyses of the HOPE trial have provided evidence for its beneficial action in the prevention of diabetes.</p> <p>Methods</p> <p>The ADaPT investigation ("ACE inhibitor-based versus diuretic-based antihypertensive primary treatment in patients with pre-diabetes") is a 4-year open, prospective, parallel group phase IV study. It compares an antihypertensive treatment regimen based on ramipril versus a treatment based on diuretics or betablockers. The primary evaluation criterion is the first manifestation of type 2 diabetes. The study is conducted in primary care to allow the broadest possible application of its results. The present article provides an outline of the rationale, the design and baseline characteristics of AdaPT and compares these to previous studies including ASCOT-BLPA, VALUE and DREAM.</p> <p>Results</p> <p>Until March 2006 a total of 2,015 patients in 150 general practices (general physicians and internists) throughout Germany were enrolled. The average age of patients enrolled was 67.1 ± 10.3 years, with 47% being male and a BMI of 29.9 ± 5.0 kg/m². Dyslipidemia was present in 56.5%. 37.8% reported a family history of diabetes, 57.8% were previously diagnosed with hypertension (usually long standing). The HbA1c value at baseline was 5.6 %. Compared to the DREAM study patients were older, had more frequently hypertension and patients with cardiovascular disease were not excluded.</p> <p>Conclusion</p> <p>Comparing the ADaPT design and baseline data to previous randomized controlled trial it can be acknowledged that AdaPT included patients with a high risk for diabetes development. Results are expected to be available in 2010. Data will be highly valuable for clinical practice due to the observational study design.</p

Ramipril-based versus diuretic-based antihypertensive primary treatment in patients with pre-diabetes (ADaPT) study

<p>Abstract</p> <p>Background</p> <p>Previous randomized controlled trials demonstrated a protective effect of renin angiotensin system blocking agents for the development of type-2 diabetes in patients with pre-diabetes. However, there are no real-world data available to illustrate the relevance for clinical practice.</p> <p>Methods</p> <p>Open, prospective, parallel group study comparing patients with an ACE inhibitor versus a diuretic based treatment. The principal aim was to document the first manifestation of type-2 diabetes in either group.</p> <p>Results</p> <p>A total of 2,011 patients were enrolled (mean age 69.1 ± 10.3 years; 51.6% female). 1,507 patients were available for the per-protocol analysis (1,029 ramipril, 478 diuretic group). New-onset diabetes was less frequent in the ramipril than in the diuretic group over 4 years. Differences were statistically different at a median duration of 3 years (24.4% vs 29.5%; p < 0.05). Both treatments were equally effective in reducing BP (14.7 ± 18.0/8.5 ± 8.2 mmHg and 12.7 ± 18.1/7.0 ± 8.3 mmHg) at the 4 year follow-up (p < 0.001 vs. baseline; p = n.s. between groups). In 38.6% and 39.7% of patients BP was below 130/80 mmHg (median time-to-target 3 months). There was a significant reduction of cardiovascular morbidity and mortality in favour of ramipril (p = 0.033). No significant differences were found for a change in HbA1c as well as for fasting blood glucose levels during follow-up. The rate of adverse events was higher in diuretic treated patients (SAE 15.4 vs. 12.4%; p < 0.05; AE 26.6 vs. 25.6%; p = n.s).</p> <p>Conclusions</p> <p>Ramipril treatment is preferable over diuretic based treatment regimens for the treatment of hypertension in pre-diabetic patients, because new-onset diabetes is delayed.</p

Diabetes incidence – results of full Bayesian network meta-analysis of 22 trials with 143153 patients , modified from

<p><b>Copyright information:</b></p><p>Taken from "First-line antihypertensive treatment in patients with pre-diabetes: Rationale, design and baseline results of the ADaPT investigation"</p><p>http://www.cardiab.com/content/7/1/22</p><p>Cardiovascular Diabetology 2008;7():22-22.</p><p>Published online 24 Jul 2008</p><p>PMCID:PMC2529270.</p><p></p

DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia

Charting differences between tumors and normal tissue is a mainstay of cancer research. However, clonal tumor expansion from complex normal tissue architectures potentially obscures cancer-specific events, including divergent epigenetic patterns. Using whole-genome bisulfite sequencing of normal B cell subsets, we observed broad epigenetic programming of selective transcription factor binding sites coincident with the degree of B cell maturation. By comparing normal B cells to malignant B cells from 268 patients with chronic lymphocytic leukemia (CLL), we showed that tumors derive largely from a continuum of maturation states reflected in normal developmental stages. Epigenetic maturation in CLL was associated with an indolent gene expression pattern and increasingly favorable clinical outcomes. We further uncovered that most previously reported tumor-specific methylation events are normally present in non-malignant B cells. Instead, we identified a potential pathogenic role for transcription factor dysregulation in CLL, where excess programming by EGR and NFAT with reduced EBF and AP-1 programming imbalances the normal B cell epigenetic program