Despite overall reductions in heart disease prevalence, the risk of developing heart failure has remained 2-fold greater among people with diabetes. Growing evidence has supported that fluctuations in glucose level and uptake contribute to cardiovascular disease (CVD) by modifying proteins, DNA, and gene expression. In the case of glucose, clinical studies have shown that increased dietary sugars for healthy individuals or poor glycemic control in diabetic patients further increased CVD risk. Furthermore, even after decades of maintaining tight glycemic control, susceptibility to disease progression can persist following a period of poor glycemic control through a process termed "glycemic memory." In response to chronically elevated glucose levels, a number of studies have identified molecular targets of the glucose-mediated protein posttranslational modification by the addition of an O-linked N-acetylglucosamine to impair contractility, calcium sensitivity, and mitochondrial protein function. Additionally, elevated glucose contributes to dysfunction in coupling glycolysis to glucose oxidation, pentose phosphate pathway, and polyol pathway. Therefore, in the "sweetened" environment associated with hyperglycemia, there are a number of pathways contributing to increased susceptibly to "breaking" the heart of diabetics. In this review we will discuss the unique contribution of glucose to heart disease and recent advances in defining mechanisms of action.

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Citations to this article as recorded by  

• Compound SJ-12 attenuates streptozocin-induced diabetic cardiomyopathy by stabilizing SERCA2a
  Shuaijie Lou, Weiwei Zhu, Tianxiang Yu, Qianhui Zhang, Minxiu Wang, Leiming Jin, Yongqiang Xiong, Jiachen Xu, Qinyan Wang, Gaozhi Chen, Guang Liang, Xiang Hu, Wu Luo
  Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2024; 1870(5): 167140.     CrossRef
• O304 ameliorates hyperglycemia in mice by dually promoting muscle glucose effectiveness and preserving β-cell function
  Stefan Norlin, Jan Axelsson, Madelene Ericsson, Helena Edlund
  Communications Biology.2023;[Epub]     CrossRef
• The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches
  Shuxian Chen, Yuanming Zou, Chunyu Song, Kexin Cao, Kexin Cai, Yanjiao Wu, Zhaobo Zhang, Danxi Geng, Wei Sun, Nanxiang Ouyang, Naijin Zhang, Zhao Li, Guozhe Sun, Yixiao Zhang, Yingxian Sun, Ying Zhang
  Basic Research in Cardiology.2023;[Epub]     CrossRef
• Silibinin ameliorates the cardiovascular oxidative and inflammatory effects of type-2-diabetic rats exposed to air particulate matter
  Olamide O. Awolaja, Akeem O. Lawal, Ibukun M. Folorunso, Olusola O. Elekofehinti, Haruna I. Umar
  Polycyclic Aromatic Compounds.2023; 43(7): 6570.     CrossRef
• The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK
  Jozaa Z. AlTamimi, Nora A. AlFaris, Ghedeir M. Alshammari, Reham I. Alagal, Dalal H. Aljabryn, Mohammed Abdo Yahya
  Nutrients.2023; 15(7): 1660.     CrossRef
• The role of CD36 in cardiovascular disease
  Hongyang Shu, Yizhong Peng, Weijian Hang, Jiali Nie, Ning Zhou, Dao Wen Wang
  Cardiovascular Research.2022; 118(1): 115.     CrossRef
• The world congress on insulin resistance, diabetes, and cardiovascular disease (WCIRDC)
  Zachary Bloomgarden
  Journal of Diabetes.2022; 14(3): 163.     CrossRef
• Pharmacological modulation of prostaglandin E2 (PGE2) EP receptors improves cardiomyocyte function under hyperglycemic conditions
  Karin J. Bosma, Monica Ghosh, Spencer R. Andrei, Lin Zhong, Jennifer C. Dunn, Valerie F. Ricciardi, Juliann B. Burkett, Antonis K. Hatzopoulos, Derek S. Damron, Maureen Gannon
  Physiological Reports.2022;[Epub]     CrossRef
• The efficacy and safety of traditional Chinese medicine treating diabetic cardiomyopathy: A protocol for systematic review and meta-analysis
  Shuo Han, Yuan Hou, Huaman Liu, Quanlin Zhao
  Medicine.2022; 101(47): e31269.     CrossRef
• High Throughput Screen Identifies Small Molecule Effectors That Modulate Thin Filament Activation in Cardiac Muscle
  Priyanka Parijat, Laszlo Kondacs, Alexander Alexandrovich, Mathias Gautel, Alexander J. A. Cobb, Thomas Kampourakis
  ACS Chemical Biology.2021; 16(1): 225.     CrossRef
• Prostaglandin E receptor subtype 4 protects against diabetic cardiomyopathy by modulating cardiac fatty acid metabolism via FOXO1/CD36 signalling
  Fan Ying, Hao Liu, Eva Hoi Ching Tang, Ishan Lakhani, Ningning Liu, Zhengyuan Xia, Shiming Liu
  Biochemical and Biophysical Research Communications.2021; 548: 196.     CrossRef
• Intracellular Toxic AGEs (TAGE) Triggers Numerous Types of Cell Damage
  Masayoshi Takeuchi, Akiko Sakasai-Sakai, Takanobu Takata, Jun-ichi Takino, Yoshiki Koriyama, Chigusa Kikuchi, Ayako Furukawa, Kentaro Nagamine, Takamitsu Hori, Tamihide Matsunaga
  Biomolecules.2021; 11(3): 387.     CrossRef
• Phosphorylated and O-GlcNAc Modified IRS-1 (Ser1101) and -2 (Ser1149) Contribute to Human Diabetes Type II
  Afshan Kaleem, Sabahat Javed, Nayab Rehman, Roheena Abdullah, Mehwish Iqtedar, Mohammad Nauman Aftab, Daniel C. Hoessli, Ikram-Ul Haq
  Protein & Peptide Letters.2021; 28(3): 333.     CrossRef
• Diabetes and Heart Failure: Multi-Omics Approaches
  Akram Tayanloo-Beik, Peyvand Parhizkar Roudsari, Mostafa Rezaei-Tavirani, Mahmood Biglar, Ozra Tabatabaei-Malazy, Babak Arjmand, Bagher Larijani
  Frontiers in Physiology.2021;[Epub]     CrossRef
• Asymptomatic Diabetic Cardiomyopathy: an Underrecognized Entity in Type 2 Diabetes
  Ana Maria Stanton, Muthiah Vaduganathan, Lee-Shing Chang, Alexander Turchin, James L. Januzzi, Vanita R. Aroda
  Current Diabetes Reports.2021;[Epub]     CrossRef
• Increased Glucose Availability Attenuates Myocardial Ketone Body Utilization
  Manoja K. Brahma, Chae‐Myeong Ha, Mark E. Pepin, Sobuj Mia, Zhihuan Sun, John C. Chatham, Kirk M. Habegger, Evan Dale Abel, Andrew J. Paterson, Martin E. Young, Adam R. Wende
  Journal of the American Heart Association.2020;[Epub]     CrossRef
• Gene therapy targeting cardiac phosphoinositide 3-kinase (p110α) attenuates cardiac remodeling in type 2 diabetes
  Darnel Prakoso, Miles J. De Blasio, Mitchel Tate, Helen Kiriazis, Daniel G. Donner, Hongwei Qian, David Nash, Minh Deo, Kate L. Weeks, Laura J. Parry, Paul Gregorevic, Julie R. McMullen, Rebecca Helen Ritchie
  American Journal of Physiology-Heart and Circulatory Physiology.2020; 318(4): H840.     CrossRef
• The Potential Role of MicroRNA in Diabetic Cardiomyopathy
  Jin Hwa Kim
  Diabetes & Metabolism Journal.2020; 44(1): 54.     CrossRef
• Re-balancing cellular energy substrate metabolism to mend the failing heart
  Jan F.C. Glatz, Miranda Nabben, Martin E. Young, P. Christian Schulze, Heinrich Taegtmeyer, Joost J.F.P. Luiken
  Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2020; 1866(5): 165579.     CrossRef
• The Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1α–Heme Oxygenase 1 Axis, a Powerful Antioxidative Pathway with Potential to Attenuate Diabetic Cardiomyopathy
  Maayan Waldman, Michael Arad, Nader G. Abraham, Edith Hochhauser
  Antioxidants & Redox Signaling.2020; 32(17): 1273.     CrossRef
• miR‑155 modulates high glucose‑induced cardiac fibrosis via the Nrf2/HO‑1 signaling pathway
  Yu Li, Jing‑Zhu Duan, Qian He, Chong‑Quan Wang
  Molecular Medicine Reports.2020;[Epub]     CrossRef
• Disruption of energy utilization in diabetic cardiomyopathy; a mini review
  Shinsuke Nirengi, Carmem Peres Valgas da Silva, Kristin I Stanford
  Current Opinion in Pharmacology.2020; 54: 82.     CrossRef
• Reduced fatty acid uptake aggravates cardiac contractile dysfunction in streptozotocin-induced diabetic cardiomyopathy
  Yogi Umbarawan, Ryo Kawakami, Mas Rizky A. A. Syamsunarno, Norimichi Koitabashi, Hideru Obinata, Aiko Yamaguchi, Hirofumi Hanaoka, Takako Hishiki, Noriyo Hayakawa, Hiroaki Sunaga, Hiroki Matsui, Masahiko Kurabayashi, Tatsuya Iso
  Scientific Reports.2020;[Epub]     CrossRef
• Metabolomics biomarkers and the risk of overall mortality and ESRD in CKD: Results from the Progredir Cohort
  Silvia M. Titan, Gabriela Venturini, Kallyandra Padilha, Alessandra C. Goulart, Paulo A. Lotufo, Isabela J. Bensenor, Jose E. Krieger, Ravi I. Thadhani, Eugene P. Rhee, Alexandre C. Pereira, Vivekanand Jha
  PLOS ONE.2019; 14(3): e0213764.     CrossRef
• Chronic hyperglycemia as a risk factor in implant therapy
  Fawad Javed, Georgios E. Romanos
  Periodontology 2000.2019; 81(1): 57.     CrossRef
• Recent advances in the pathogenesis of microvascular complications in diabetes
  Sungmi Park, Hyeon-Ji Kang, Jae-Han Jeon, Min-Ji Kim, In-Kyu Lee
  Archives of Pharmacal Research.2019; 42(3): 252.     CrossRef
• Nutrient regulation of signaling and transcription
  Gerald W. Hart
  Journal of Biological Chemistry.2019; 294(7): 2211.     CrossRef
• Intracellular toxic advanced glycation end-products in cardiomyocytes may cause cardiovascular disease
  Takanobu Takata, Akiko Sakasai-Sakai, Tadashi Ueda, Masayoshi Takeuchi
  Scientific Reports.2019;[Epub]     CrossRef
• Effects of Exercise to Improve Cardiovascular Health
  Kelsey Pinckard, Kedryn K. Baskin, Kristin I. Stanford
  Frontiers in Cardiovascular Medicine.2019;[Epub]     CrossRef
• A new hyperpolarized 13C ketone body probe reveals an increase in acetoacetate utilization in the diabetic rat heart
  Desiree Abdurrachim, Chern Chiuh Woo, Xing Qi Teo, Wei Xin Chan, George K. Radda, Philip Teck Hock Lee
  Scientific Reports.2019;[Epub]     CrossRef
• Chronic O-GlcNAcylation and Diabetic Cardiomyopathy: The Bitterness of Glucose
  Simon Ducheix, Jocelyne Magré, Bertrand Cariou, Xavier Prieur
  Frontiers in Endocrinology.2018;[Epub]     CrossRef
• Proteomics of the Rat Myocardium during Development of Type 2 Diabetes Mellitus Reveals Progressive Alterations in Major Metabolic Pathways
  Anders Valdemar Edhager, Jonas Agerlund Povlsen, Bo Løfgren, Hans Erik Bøtker, Johan Palmfeldt
  Journal of Proteome Research.2018; 17(7): 2521.     CrossRef
• Protective effects of astaxanthin on diabetic cardiomyopathy in rats
  Bingshan Zhang, Di Xu
  CyTA - Journal of Food.2018; 16(1): 909.     CrossRef
• Au cœur de la cardiomyopathie diabétique
  Alexandre Lugat, Michael Joubert, Bertrand Cariou, Xavier Prieur
  médecine/sciences.2018; 34(6-7): 563.     CrossRef
• Redox imbalance stress in diabetes mellitus: Role of the polyol pathway
  Liang‐jun Yan
  Animal Models and Experimental Medicine.2018; 1(1): 7.     CrossRef
• Heart rate dynamics during cardio-pulmonary exercise testing are associated with glycemic control in individuals with type 1 diabetes
  Othmar Moser, Max L. Eckstein, Olivia McCarthy, Rachel Deere, Stephen C. Bain, Hanne L. Haahr, Eric Zijlstra, Tim Heise, Richard M. Bracken, Petter Bjornstad
  PLOS ONE.2018; 13(4): e0194750.     CrossRef
• Resistance exercise improves cardiac function and mitochondrial efficiency in diabetic rat hearts
  Tae Hee Ko, Jubert C. Marquez, Hyoung Kyu Kim, Seung Hun Jeong, SungRyul Lee, Jae Boum Youm, In Sung Song, Dae Yun Seo, Hye Jin Kim, Du Nam Won, Kyoung Im Cho, Mun Gi Choi, Byoung Doo Rhee, Kyung Soo Ko, Nari Kim, Jong Chul Won, Jin Han
  Pflügers Archiv - European Journal of Physiology.2018; 470(2): 263.     CrossRef
• Adriamycin-induced cardiomyopathy can serve as a model for diabetic cardiomyopathy – a hypothesis
  Kaviyarasi Renu, V.G. Abilash, P.B. Tirupathi Pichiah, Thabassum Akthar Syeda, Sankarganesh Arunachalam
  Asian Pacific Journal of Tropical Biomedicine.2017; 7(11): 1041.     CrossRef
• Proteome profiling in the aorta and kidney of type 1 diabetic rats
  Moustafa Al Hariri, Mohamad Elmedawar, Rui Zhu, Miran A. Jaffa, Jingfu Zhao, Parvin Mirzaei, Adnan Ahmed, Firas Kobeissy, Fuad N. Ziyadeh, Yehia Mechref, Ayad A. Jaffa, Michael Bader
  PLOS ONE.2017; 12(11): e0187752.     CrossRef