May 24, 1999 CHAPEL HILL - For the first time, researchers working at the University of North Carolina at Chapel Hill have uncovered major evidence that inflammation plays an undefined but central role in development of Type 2 diabetes.
Eventually, doctors might be able to use various laboratory test results -- or markers -- for inflammation to predict who is at a higher risk of developing what's also called diabetes mellitus in mid- or later life, the scientists say.
Their study, conducted on 12,330 men and women, ages 45 to 64, in Maryland, Minnesota, Mississippi and North Carolina, also suggests physicians could delay or prevent some people getting diabetes through strict weight control since fat cells produce inflammatory mediators.
A report on the research appears in the current (May 15) issue of the Lancet, a British medical journal. Authors include Drs. Maria Ines Schmidt and Bruce B. Duncan of the Federal University of Rio Grande do Sul in Brazil, who participated in the study while visiting professors at UNC-CH, Dr. Steven Offenbacher of the UNC-CH School of Dentistry and Dr. Gerardo Heiss of the UNC-CH School of Public Health.
"Inflammation's role in the development of heart disease has been investigated extensively," Schmidt said. "Some basic science studies have suggested a possible causal connection between inflammation and diabetes, but as far as we know, this is the first evidence that these basic science findings may indeed have major implications for populations."
"We think the vast majority of scientists and physicians working with diabetes will be surprised by these findings because inflammation has not been recognized as being important to development of this illness," Duncan said. "Although the findings have no immediate clinical application, they point the way to an exciting new area of research in the causation of one of the world's major health problems."
Among subjects studied, researchers identified 1,335 new cases of Type 2 diabetes. After adjusting for various risk factors, they found that those with white blood cell counts in the highest 25 percent of the sample faced almost twice the risk of developing the illness as those with white cell counts in the lowest 25 percent of the sample.
Volunteers with the lowest levels of albumin, a common protein in blood that decreases during inflammation, faced about a 30 percent higher risk of developing diabetes than those with the highest albumin levels. Those with the highest fibrinogen - a protein produced in the liver during inflammation and important to blood clotting -- showed about a 20 percent higher risk, after accounting for other factors.
The inflammation described was most likely mild and sub-clinical, as white blood cell, albumin and fibrinogen levels of almost the entire group were within clinically accepted normal ranges at the time of their measurement, the scientists said.
In a study of a smaller sample of 610 volunteers, half of whom showed atherosclerosis or "hardening of the arteries" and half of whom did not, investigators found 33 new cases of diabetes Type 2. Those with above-average levels of two specific measures of the body's inflammatory response --orosomucoid and sialic acid -- faced even higher risks of developing the condition. Orosomucoid is a protein produced by the liver following inflammatory stress. Sialic acid is a carbohydrate attached to a series of proteins made by the liver in reaction to such stress.
"A lot more research on this issue needs to be done because we should be able to find other markers to predict diabetes more accurately and to intervene sooner," Schmidt said. "More work also could suggest new ways of preventing or managing the disease through drugs or other methods."
The National Heart, Lung and Blood Institute supported the research as part of the continuing UNC-CH School of Public Health-based Atherosclerosis Risk in Communities (ARIC) study.
More than 15,000 subjects were originally recruited in 1987 from four geographically diverse U.S. communities -- Washington County, Md.; Jackson, Miss.; Minneapolis, Minn.; and Forsyth County, N.C. UNC-CH researchers and their colleagues have been following up on and analyzing the volunteers' periodic medical examinations ever since, emphasizing heart disease and factors that contribute to its development.
Other authors of the new study are Drs. A. Richey Sharrett and Peter J. Savage of the National Heart, Lung and Blood Institute, Gunnar Lindberg of Malmo Hospital in Sweden, Maria Ines Azambuja of the Federal University in Porto Alegre, Brazil, and Russell P. Tracy of the Unversity of Vermont.
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