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Linking Kidney and Cardiovascular Complications in Diabetes-Impact on Prognostication and Treatment: The 2019 Edwin Bierman Award Lecture.

ABSTRACT: In diabetes, increasing albuminuria and decreasing glomerular filtration rate are hallmarks of chronic kidney disease in diabetes and increase the risk of atherosclerotic cardiovascular events and mortality as well as the risk for end-stage kidney disease. For two decades, standard of care has been controlling risk factors, such as glucose, blood pressure, lipids, and lifestyle factors, and specifically use of agents blocking the renin-angiotensin system. This has improved outcome, but a large unmet need has been obvious. After many failed attempts to advance the therapeutic options, the past few years have provided several new promising treatment options such as sodium-glucose cotransporter 2 inhibitors, endothelin receptor antagonists, glucagon-like peptide 1 agonists, and nonsteroidal mineralocorticoid receptor antagonists. The benefits and side effects of these agents demonstrate the link between kidney and heart; some have beneficial effects on both, whereas for other potentially renoprotective agents, development of heart failure has been a limiting factor. They work on different pathways such as hemodynamic, metabolic, inflammatory, and fibrotic targets. We propose that treatment may be personalized if biomarkers or physiological investigations assessing activity in these pathways are applied. This could potentially pave the way for precision medicine, where treatment is optimized for maximal benefit and minimal adverse outcomes. At least it may help prioritizing agents for an individual subject.

SUBMITTER: Rossing P

PROVIDER: S-EPMC7881849 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The Edwin Bierman Award Lecture is presented in honor of the memory of Edwin L. Bierman, MD, an exemplary scientist, mentor, and leader in the field of diabetes, obesity, hyperlipidemia, and atherosclerosis. The award and lecture recognizes a leading scientist in the field of macrovascular complications and contributing risk factors in diabetes. Clay F. Semenkovich, MD, the Irene E. and Michael M. Karl Professor and Chief of the Division of Endocrinology, Metabolism and Lipid Research at Washington University School of Medicine in St. Louis, St. Louis, MO, received the prestigious award at the American Diabetes Association's 76th Scientific Sessions, 10-14 June 2016, in New Orleans, LA. He presented the Edwin Bierman Award Lecture, "We Know More Than We Can Tell About Diabetes and Vascular Disease," on Sunday, 12 June 2016.Diabetes is a disorder of abnormal lipid metabolism, a notion strongly supported by the work of Edwin Bierman, for whom this eponymous lecture is named. This abnormal lipid environment continues to be associated with devastating vascular complications in diabetes despite current therapies, suggesting that our understanding of the pathophysiology of blood vessel disease in diabetes is limited. In this review, potential new insights into the nature of diabetic vasculopathy will be discussed. Recent observations suggest that while the concept of distinct macrovascular and microvascular complications of diabetes has been useful, vascular diseases in diabetes may be more interrelated than previously appreciated. Moreover, the intermediary metabolic pathway of de novo lipogenesis, which synthesizes lipids from simple precursors, is robustly sensitive to insulin and may contribute to these complications. De novo lipogenesis requires fatty acid synthase, and recent studies of this enzyme suggest that endogenously produced lipids are channeled to specific intracellular sites to affect physiology. These findings raise the possibility that novel approaches to treating diabetes and its complications could be based on altering the intracellular lipid milieu.

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Linking Kidney and Cardiovascular Complications in Diabetes-Impact on Prognostication and Treatment: The 2019 Edwin Bierman Award Lecture.

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