1. Date of download: 6/23/2016 Copyright © The American College of Cardiology. All rights reserved. From: Impact of Diabetes on Epidemiology, Treatment, and Outcomes of Patients With Heart Failure JCHF. 2015;3(2):136-145. doi:10.1016/j.jchf.2014.08.004 Pathophysiologic Abnormalities in Diabetes and Heart Failure Multiple pathophysiologic mechanisms are activated and modulated by the presence of diabetes mellitus, resulting in abnormalities in the myocardial substrate unique to patients with diabetes mellitus and heart failure. Adapted with permission from Falcao-Pires I, Leite-Moreira AF. Heart Fail Rev 2012;17:325–44. AGE = advanced glycation end product; FFA = free fatty acid; GLUT = glucose transporter facilitators; PDH = pyruvate dehydrogenase; PKC = protein kinase C; PPAR = peroxisome proliferator-activated receptor; RAAS = renin-angiotensin-aldosterone system; REDOX = oxidation and reduction; ROS = reactive oxygen species; TG = triglyceride; VGEF = vascular endothelial growth factor. Figure Legend:

2. Date of download: 6/23/2016 Copyright © The American College of Cardiology. All rights reserved. From: Impact of Diabetes on Epidemiology, Treatment, and Outcomes of Patients With Heart Failure JCHF. 2015;3(2):136-145. doi:10.1016/j.jchf.2014.08.004 Echocardiographic Abnormalities in Diabetes and Heart Failure An example from a diabetic patient with a high global contrast-enhanced myocardial T1 time (508 ms), suggesting less interstitial fibrosis and a corresponding global longitudinal strain of −19.0% (left) with normal left ventricular ejection fraction of 60% for both. Figure Legend:

3. Date of download: 6/23/2016 Copyright © The American College of Cardiology. All rights reserved. From: Impact of Diabetes on Epidemiology, Treatment, and Outcomes of Patients With Heart Failure JCHF. 2015;3(2):136-145. doi:10.1016/j.jchf.2014.08.004 Immunohistochemical Abnormalities in Diabetes and Heart Failure Immunohistochemical study of the biopsied myocardium in a patient with diabetes demonstrates interstitial fibrosis with substantial accumulation of collagen with perimysial fibrosis (A), endomysial fibrosis (B), and perivascular fibrosis (C) stained with Mallory’s AZAN trichrome method. Figure Legend:

4. Date of download: 6/23/2016 Copyright © The American College of Cardiology. All rights reserved. From: Impact of Diabetes on Epidemiology, Treatment, and Outcomes of Patients With Heart Failure JCHF. 2015;3(2):136-145. doi:10.1016/j.jchf.2014.08.004 Heart Failure Rates in Diabetes Clinical Trials Differences in overall heart failure (HF) event rates are shown in contemporary clinical diabetes trials. Figure Legend: