Common Diabetes Drug Lowers Heart-Disease Risk by Inhibiting Proinflammatory Factor, UB Study Show

BUFFALO, N.Y. -- University at Buffalo endocrinologists have shown for the first time that the concentration of a proinflammatory compound known as MIF is increased in the blood plasma of the obese, and that metformin, a standard medicine prescribed for diabetes, suppresses its formation.

The findings are among the latest in series of UB studies of the anti-inflammatory potential of insulin and insulin sensitizers and their ability to decrease proinflammatory components in the blood stream linked to heart disease in diabetics and the obese.

They were presented at the 85th annual meeting of the Endocrine Society held recently in Philadelphia and at the preceding American Diabetes Association meeting in New Orleans.

Metformin is an insulin sensitizer prescribed for diabetics, but it also has been shown to lower heart-disease mortality in these patients, said Paresh Dandona, M.D., professor in the Department of Medicine in the UB School of Medicine and Biomedical Sciences and lead author on the study.

"Nobody knew the mechanism responsible for this favorable effect on heart disease," he said. "We have shown that metformin suppresses the circulating inflammatory factor MIF, which contributes to blocked arteries. When we administered metformin, MIF concentrations came hurtling down."

Persons with Type 2 diabetes develop a condition known as insulin insensitivity early in the disease process. Cells that normally would allow insulin to transport glucose from the blood stream to the liver for storage until it is needed as body fuel no longer respond to insulin, resulting in a toxic build up of glucose in the blood stream, which damages tissue lining blood vessels. Such damage leads to vessel-wall inflammation and eventually to blocked arteries.

Obesity is a risk factor for Type 2 diabetes, because increased storage of fat molecules in fatty tissue is linked to insulin resistance. Metformin is prescribed for Type 2 diabetes to inhibit glucose production in the liver and increase insulin sensitivity.

Researchers at Kaleida Health's Diabetes-Endocrinology Center of Western New York, which Dandona directs, measured fasting levels of the proinflammatory factor MIF (macrophage migration inhibitory factor) in blood samples from 40 obese and 40 normal-weight study participants. Results showed that the average concentration of MIF in the obese was twice that of the normal-weight participants.

Nine of the obese subjects then underwent a six-week course of metformin treatment. Results showed that the mean plasma concentration of MIF had fallen by 20 percent at the end of six weeks, compared to baseline.

"This action of metformin may help prevent atherosclerosis," said Dandona, "and may explain why persons with Type 2 diabetes who are treated with metformin are at lower risk of dying from heart disease."

Also contributing to the study were Ahmad Aljada, Ph.D., UB research assistant professor of medicine; Deborah Hofmeyer, UB research assistant; Priya Mohanty, M.D., UB clinical instructor of medicine; Chandana Tripathy, M.D., UB medical resident, and Ajay Chaudhuri, M.D., UB assistant professor of medicine, all from the Diabetes-Endocrinology Center of Western New York of Kaleida Health.