Reduced post-operative DPP4 activity associated with worse patient outcome after cardiac surgery
SCIENTIFIC REPORTS
Authors: Noels, Heidi; Theelen, Wendy; Sternkopf, Marieke; Jankowski, Vera; Moellmann, Julia; Kraemer, Sandra; Lehrke, Michael; Marx, Nikolaus; Martin, Lukas; Marx, Gernot; Jankowski, Joachim; Goetzenich, Andreas; Stoppe, Christian
Abstract
Cardiac surgery with cardiopulmonary bypass (CPB) triggers myocardial ischemia/reperfusion injury contributing to organ dysfunction. Preclinical studies revealed that dipeptidyl peptidase (DPP4) inhibition is protective during myocardial infarction. Here, we assessed for the first time the relation of peri-operative DPP4-activity in serum of 46 patients undergoing cardiac surgery with patients' postoperative organ dysfunction during intensive care unit (ICU) stay. Whereas a prior myocardial infarction significantly reduced pre-operative DDP4-activity, patients with preserved left ventricular function showed an intra-operative decrease of DPP4-activity. The latter correlated with aortic cross clamping time, indicative for the duration of surgery-induced myocardial ischemia. As underlying mechanism, mass-spectrometry revealed increased DPP4 oxidation by cardiac surgery, with DPP4 oxidation reducing DPP4-activity in vitro. Further, post-operative DPP4-activity was negatively correlated with the extent of post-operative organ injury as measured by SAPS II and SOFA scoring, circulating levels of creatinine and lactate, as well as patients' stay on the ICU. In conclusion, cardiac surgery reduces DPP4-activity through oxidation, with low post-operative DPP4-activity being associated with organ dysfunction and worse outcome of patients during the post-operative ICU stay. This likely reflects the severity of myocardial ischemia/reperfusion injury and may suggest potential beneficial effects of anti-oxidative treatments during cardiac surgery.
DPP4 Inhibitors in the Management of Hospitalized Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
ADVANCES IN THERAPY
Authors: Rabizadeh, Soghra; Tavakoli Ardakani, Mohammad Ali; Mouodi, Marjan; Bitaraf, Masoume; Shab-Bidar, Sakineh; Esteghamati, Alireza; Nakhjavani, Manouchehr
Abstract
Introduction We studied the effects of dipeptidyl peptidase 4 (DPP4) inhibitors on glycemic control in non-critically ill patients admitted to hospital. Methods We searched MEDLINE and EMBASE for published studies in English up to July 2019. We included randomized clinical trials (RCTs) that compared DPP4 inhibitors plus insulin supplementation versus basal-bolus insulin regimen in the management of hyperglycemia non-critically ill patients with type 2 diabetes admitted to hospital. Mean difference (MD), relative risk (RR), and 95% confidence intervals (CI) were generated to interpret the data. Results Of 401 papers, four RCTs including 648 participants met inclusion criteria. There was no significant difference in mean daily blood glucose level between the two groups (MD 4.63; 95% CI = - 1.57, 10.83;p = 0.14) (I-2 = 14%,p = 0.32). Total insulin dose per day was lower in patients receiving DPP4 inhibitors (MD - 14.27; CI = - 22.47, - 6.07;p = 0.001) (I-2 = 92%,p = 0.001). Also, the number of insulin injection was significantly lower in patients receiving DPP4 inhibitors (MD - 0.79; CI = - 1.01, - 0.57;p = 0.001) (I-2 = 0%,p = 0.68). The rate of hypoglycemia was not significantly different between the two groups (RR 0.60, CI = 0.34, 1.074;p = 0.08) (I-2 = 37.3%,p = 0.18). Treatment failure was not significantly different between the two groups (RR 0.87, CI = 0.64, 4.8;p = 0.38) (I-2 = 49%,p = 0.11). Conclusion The results indicate that using DPP4 inhibitors plus basal or supplemental insulin in hospitalized patients is non-inferior to a standard basal-bolus insulin regimen and leads to a lower amount of insulin use and a lower rate of insulin injection. Limitations of this study were heterogeneity of baseline characteristics of included patients, small sample size, short duration, and non-uniformly defined outcome assessment parameters in the included studies.