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GIK therapy
reduces inflammation post-MI "This
study shows for the first time that a low dose of insulin infused into patients
with heart attacks may reduce damage to their heart by 50%," said senior
investigator Dr Paresh
Dandona (State University of New York,
Several
studies have found that glucose-insulin-potassium (GIK) infusions can provide
additional benefit on top of drug therapy in patients with ST-segment-elevation
MI (STEMI). For instance, the Glucose-Insulin-Potassium
Study (GIPS), the largest prospective randomized trial on this
therapy to date, presented first at the European
Society of Cardiology Congress 2002, found a significant reduction
in 30-day mortality with GIK infusions in STEMI patients with no heart-failure
symptoms, as reported by heartwire. Based on the
knowledge that increased glucose uptake takes place during myocardial ischemia,
the concept of metabolically protecting the myocardium via GIK therapy has been
under investigation for several decades. However, trial results so far have
been contradictory. In addition to the GIPS trial, positive results were apparent
in ECLA, published in 1998, and DIGAMI, published in 1995. First study on effects of insulin and markers of inflammation
Dr Ajay Chaudhuri and
colleagues at SUNY Buffalo found that insulin reduced inflammation in
endothelial cells in vitro and in circulating mononuclear cells in obese and nondiabetic subjects. Based on these earlier findings and
on the fact that MI is an inflammatory state, they hypothesized that low-dose
infusions of insulin in MI-patients might have an anti-inflammatory effect,
which could account for the observed benefit of GIK therapy in GIPS and other
studies. "We postulated that insulin might do something useful, perhaps as
a drug," Dandona said in an interview with heartwire. In the
first study on the effect of insulin infusions on inflammatory markers, they
assigned 32 patients presenting to the emergency room with acute STEMI to
either a GIK infusion (10% dextrose with 40-mmol KCl
at 60 mL/h and insulin at 2.5 U/h) or to a standard
saline and potassium solution after reteplase administration.
All patients received intravenous reteplase, unfractionated heparin, and aspirin within 30 minutes of
arrival, plus other prescribed medications. The researchers measured plasma concentrations of
inflammatory markers, including C-reactive protein (CRP), serum amyloid (SAA), plasminogen
activator-1 (PAI-1), and creatine kinase
(CK) at baseline and sequentially for 48 hours. CRP,
SAA, and PAI-1 increased significantly in both groups, but absolute increases
at 24 and 48 hours in all three markers were substantially smaller in patients
who had received insulin infusions. Specifically, increases in CRP were reduced
by 40% and increases of SAA by 50%, which supports the hypothesis of an
anti-inflammatory effect of insulin. This, Chaudhuri
et al propose, could in part explain the beneficial effect of GIK infusions
observed in earlier studies. However, they point out that a reduction in
infarct size could also have accounted for the reductions in CRP. This issue,
they say, warrants further investigation in larger studies. CK,
which is released during MI and reflects myocardial damage, was reduced by 60%
in the insulin group, and more insulin-treated patients (82%) than controls
(62%) achieved ST-segment resolution of >50%, although they received thrombolytics 72 hours later, "an effect comparable to
the addition of abciximab to thrombolytics
in the TIMI 14 trial," Chaudhuri and colleagues write. Interestingly, GP IIb/IIIa inhibitors, statins, and
ACE inhibitors did not influence inflammatory parameters, the authors note.
"Infusing
insulin at low doses along with antithrombotic agents
reduces the amount of increase in inflammation and rapidly suppresses the
increase in factors that interfere with clot-dissolving medication," Dandona explained. These effects, he said, could improve
blood flow during MI and limit cardiac tissue damage. His group found it
"quite startling" that insulin may have prevented heart-tissue damage.
Larger studies, he explained to heartwire,
need to further explore the extent of protection that could be achieved with
insulin therapy. His group is scheduled to launch a 200-patient trial next
month, and a multicenter NIH-mediated trial looking at long-term outcomes is also
planned, he said. He is convinced that insulin infusions will be implemented
into clinical practice, even to prevent the onset of MI in patients reporting
to the ER with chest pain. "I believe it should already be in clinical practice,
because it protects 50% of your heart muscle," he said. | ||||||||||||||||||
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