Heart Failure in Type 2 Diabetes Mellitus.
Authors Kenny HC, Abel ED
Submitted By Submitted Externally on 4/8/2019
Status Published
Journal Circulation research
Year 2019
Date Published 1/1/2019
Volume : Pages 124 : 121 - 141
PubMed Reference 30605420
Abstract Patients with diabetes mellitus have >2× the risk for developing heart failure
(HF; HF with reduced ejection fraction and HF with preserved ejection fraction).
Cardiovascular outcomes, hospitalization, and prognosis are worse for patients
with diabetes mellitus relative to those without. Beyond the structural and
functional changes that characterize diabetic cardiomyopathy, a complex
underlying, and interrelated pathophysiology exists. Despite the success of many
commonly used antihyperglycemic therapies to lower hyperglycemia in type 2
diabetes mellitus the high prevalence of HF persists. This, therefore, raises
the possibility that additional factors beyond glycemia might contribute to the
increased HF risk in diabetes mellitus. This review summarizes the state of
knowledge about the impact of existing antihyperglycemic therapies on HF and
discusses potential mechanisms for beneficial or deleterious effects. Second, we
review currently approved pharmacological therapies for HF and review evidence
that addresses their efficacy in the context of diabetes mellitus. Dysregulation
of many cellular mechanisms in multiple models of diabetic cardiomyopathy and in
human hearts have been described. These include oxidative stress, inflammation,
endoplasmic reticulum stress, aberrant insulin signaling, accumulation of
advanced glycated end-products, altered autophagy, changes in myocardial
substrate metabolism and mitochondrial bioenergetics, lipotoxicity, and altered
signal transduction such as GRK (g-protein receptor kinase) signaling, renin
angiotensin aldosterone signaling and ß-2 adrenergic receptor signaling. These
pathophysiological pathways might be amenable to pharmacological therapy to
reduce the risk of HF in the context of type 2 diabetes mellitus. Successful
targeting of these pathways could alter the prognosis and risk of HF beyond what
is currently achieved using existing antihyperglycemic and HF therapeutics.

Complications