Managing diabetes mellitus is an ongoing concern, especially in the
presence of heart failure. Recent reports have drawn attention to
adverse cardiovascular events associated with the use of
thiazolidinediones, including rosiglitazone (Avandia). In 2011, the U.S.
Food and Drug Administration implemented a stringent"restricted access
program"for the prescription of Avandia. Other studies, which have
revealed increased mortality rates in association with tight glycemic
control, raise serious concerns about managing diabetes in heart-failure
patients.Herein, we provide a perspective on the management of
noninsulin-dependent diabetes in patients with heart failure. We point
out that thiazolidinediones exert their major effects through insulin
sensitization, which potentiates the action of insulin. A defining
feature of insulin resistance is excess fuel supply and restricted rates
of substrate utilization by the heart. We postulate that the use of
excess insulin and insulin-sensitizing agents can lead to adverse
cardiovascular events and contractile dysfunction through an increase of
substrate uptake to an insulin-resistant heart that is already flooded
with fuel. We include a table of antidiabetic agents and
nonpharmacologic interventions aimed at lowering substrate supply, and
of the respective clinical trials supporting their safety and efficacy.
Although previously contraindicated in patients with heart failure,
metformin appears to be both safe and effective therapy for diabetes in
those patients. Because metformin reduces gluconeogenesis in the liver,
we propose that the management of diabetes in heart-failure patients
should target the source, rather than the destination, of excess fuel.
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