@article{ZinmanInzucchiLachinetal.2014,
  author    = {Zinman, Bernard and Inzucchi, Silvio E. and Lachin, John M. and Wanner, Christoph and Ferrari, Roberto and Fitchett, David and Bluhmki, Erich and Hantel, Stefan and Kempthorne-Rawson, Joan and Newman, Jennifer and Johansen, Odd Erik and Woerle, Hans-Juergen and Broedl, Uli C.},
  title     = {Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME (TM))},
  series = {Cardiovascular Diabetology},
  volume    = {13},
  journal   = {Cardiovascular Diabetology},
  number    = {102},
  issn      = {1475-2840},
  doi       = {10.1186/1475-2840-13-102},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116036},
  year      = {2014},
  abstract  = {Background: Evidence concerning the importance of glucose lowering in the prevention of cardiovascular (CV) outcomes remains controversial. Given the multi-faceted pathogenesis of atherosclerosis in diabetes, it is likely that any intervention to mitigate this risk must address CV risk factors beyond glycemia alone. The SGLT-2 inhibitor empagliflozin improves glucose control, body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes. The aim of the ongoing EMPA-REG OUTCOME (TM) trial is to determine the long-term CV safety of empagliflozin, as well as investigating potential benefits on macro-/microvascular outcomes. Methods: Patients who were drug naive (HbA(1c) >= 7.0\% and <= 9.0\%), or on background glucose-lowering therapy (HbA(1c) >= 7.0\% and <= 10.0\%), and were at high risk of CV events, were randomized (1:1:1) and treated with empagliflozin 10 mg, empagliflozin 25 mg, or placebo (double blind, double dummy) superimposed upon the standard of care. The primary outcome is time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke. CV events will be prospectively adjudicated by an independent Clinical Events Committee. The trial will continue until >= 691 confirmed primary outcome events have occurred, providing a power of 90\% to yield an upper limit of the adjusted 95\% CI for a hazard ratio of <1.3 with a one-sided a of 0.025, assuming equal risks between placebo and empagliflozin (both doses pooled). Hierarchical testing for superiority will follow for the primary outcome and key secondary outcomes (time to first occurrence of CV death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina pectoris) where non-inferiority is achieved. Results: Between Sept 2010 and April 2013, 592 clinical sites randomized and treated 7034 patients (41\% from Europe, 20\% from North America, and 19\% from Asia). At baseline, the mean age was 63 +/- 9 years, BMI 30.6 +/- 5.3 kg/m(2), HbA1c 8.1 +/- 0.8\%, and eGFR 74 +/- 21 ml/min/1.73 m(2). The study is expected to report in 2015. Discussion: EMPA REG OUTCOME (TM) will determine the CV safety of empagliflozin in a cohort of patients with type 2 diabetes and high CV risk, with the potential to show cardioprotection.},
  language  = {en}
}
@article{HeldMittnachtKolbetal.2014,
  author    = {Held, Matthias and Mittnacht, Maria and Kolb, Martin and Karl, Sabine and Jany, Berthold},
  title     = {Pulmonary and Cardiac Function in Asymptomatic Obese Subjects and Changes following a Structured Weight Reduction Program: A Prospective Observational Study},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {9},
  doi       = {10.1371/journal.pone.0107480},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119239},
  pages     = {e107480},
  year      = {2014},
  abstract  = {Background The prevalence of obesity is rising. Obesity can lead to cardiovascular and ventilatory complications through multiple mechanisms. Cardiac and pulmonary function in asymptomatic subjects and the effect of structured dietary programs on cardiac and pulmonary function is unclear. Objective To determine lung and cardiac function in asymptomatic obese adults and to evaluate whether weight loss positively affects functional parameters. Methods We prospectively evaluated bodyplethysmographic and echocardiographic data in asymptomatic subjects undergoing a structured one-year weight reduction program. Results 74 subjects (32 male, 42 female; mean age 42±12 years) with an average BMI 42.5±7.9, body weight 123.7±24.9 kg were enrolled. Body weight correlated negatively with vital capacity (R = -0.42, p<0.001), FEV1 (R = -0.497, p<0.001) and positively with P 0.1 (R = 0.32, p = 0.02) and myocardial mass (R = 0.419, p = 0.002). After 4 months the study subjects had significantly reduced their body weight (-26.0±11.8 kg) and BMI (-8.9±3.8) associated with a significant improvement of lung function (absolute changes: vital capacity +5.5±7.5\% pred., p<0.001; FEV1+9.8±8.3\% pred., p<0.001, ITGV+16.4±16.0\% pred., p<0.001, SR tot -17.4±41.5\% pred., p<0.01). Moreover, P0.1/Pimax decreased to 47.7\% (p<0.01) indicating a decreased respiratory load. The change of FEV1 correlated significantly with the change of body weight (R = -0.31, p = 0.03). Echocardiography demonstrated reduced myocardial wall thickness (-0.08±0.2 cm, p = 0.02) and improved left ventricular myocardial performance index (-0.16±0.35, p = 0.02). Mitral annular plane systolic excursion (+0.14, p = 0.03) and pulmonary outflow acceleration time (AT +26.65±41.3 ms, p = 0.001) increased. Conclusion Even in asymptomatic individuals obesity is associated with abnormalities in pulmonary and cardiac function and increased myocardial mass. All the abnormalities can be reversed by a weight reduction program.},
  language  = {en}
}