Insulin decreases inflammation, aids clot-busting drugs in heart attack patients, UB study shows

February 23, 2004

BUFFALO, N.Y. -- Incorporating insulin into the mix of clot-busting and anticoagulation drugs administered to a patient suffering a heart attack significantly lowers the amount of inflammation in the blood vessels following the attack, a response that can improve a patient's chances of survival, a study conducted by researchers from the University at Buffalo has shown.

The study is the first to show that insulin can reduce concentrations of C-reactive protein (CRP) and serum amyloid A (SAA), two critical markers of inflammation, by 40 percent and 50 percent, respectively, during the 48 hours following a heart attack.

Concentrations of three additional inflammatory factors also were significantly lower in patients who received insulin compared to those who did not.

Results of the study will appear in the Feb. 24 issue of Circulation.

"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 percent," said Paresh Dandona, M.D., Ph.D., UB professor of medicine and senior author on the study. "This study will lead to further similar investigations on the use of insulin for heart attacks, stroke and acute coronary syndromes."

In earlier studies with obese patients, Dandona's research group showed that insulin exerts a significant anti-inflammatory effect on blood vessel walls, and their findings linked insulin with mechanisms that reduce clotting factors. Those findings suggested that insulin might help prevent clotting and promote dissolution of clots in persons with heart attack and stroke.

The current findings prove that hypothesis to be correct, Dandona said. The study involved 32 patients who came to the emergency department of Kaleida Health's Millard Fillmore Hospital in Buffalo suffering from a heart attack. Patients were assigned alternately to an insulin group or control group.

All patients received the clot-busting drug reteplase, plus any other prescribed medications, intravenously. The intervention group also received an infusion solution of insulin, glucose (to maintain normal glucose levels) and potassium following the reteplase administration, while the control group received a standard saline solution. Insulin was infused at a low dose continuously over 48 hours.

Analysis of blood samples collected at baseline and at several points during the 48 hours showed that concentrations of both inflammatory markers CRP and SAA rose significantly during the treatment period, a normal response to tissue injury caused by a heart attack. CRP has been shown to increase the amount of heart tissue damaged by a heart attack, and elevations of both CRP and SAA are associated with adverse outcomes in heart-attack patients, Dandona noted.

In patients who received insulin, both CRP and SAA increased significantly less. Insulin also appeared to stem the increase of a factor called plasminogen activator inhibitor, or PAI-1, which has been shown to hinder the ability of clot-busting drugs to open blocked vessels.

In addition, creatinine kinase, a protein contained in the heart muscle that is released during a heart attack, was reduced by 60 percent in the group infused with insulin, an indication that insulin protects the heart muscle during a heart attack, Dandona said.

"Infusing insulin at low doses along with antithrombotic agents reduces the amount of increase in inflammation and rapidly suppresses the increase of factors than interfere with clot-dissolving medication," said Dandona. "We think that these effects, along with insulin's known capacity to dilate blood vessels and prevent platelet clumping, could improve blood flow during a heart attack and help limit the damage to heart tissue."

He said further research is needed to determine the precise action of insulin responsible for its effect on the destructive inflammatory agents.

Also contributing to the research were Ajay Chaudhuri, M.B.B.S, M.R.C.P.; David Janicke, M.D., Ph.D.; Michael Wilson, M.D.; Devjit Tripathy, M.D.; Rejech Garg, M.D.; Arindi Bandyopadhyay, M.D.; Janeen Calieri; Debbie Hoffmeyer; Tufail Syed, M.B.B.S.; Husam Ghanim, and Ahmad Aljada, Ph.D., all from the UB Division of Endocrinology, Diabetes and Metabolism.
The research was supported in part by an educational grant from Novo Nordisk Pharmaceuticals.

The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. UB's more than 27,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs.

University at Buffalo

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