Evidence pointing to chronic cellular inflammation as the precursor of heart disease and diabetes

Endocrinologists from the University at Buffalo are providing one more link in the growing chain of evidence pointing to chronic cellular inflammation as the precursor of heart disease and diabetes.

In research published in the Sept 21 issue of Circulation, the researchers show for the first time that circulating mononuclear cells -- the body's monocytes (the largest type of white blood cell) and lymphocytes -- exist in a proinflammatory state in obese persons known to be at increased risk of developing diabetes, heart disease or both.

"These cells are creating a lot of nuisance in the obese," said Paresh Dandona, M.D., Ph.D., head of UB's Division of Endocrinology, Diabetes and Metabolism and senior author on the study. "They enter the artery and set up atherosclerosis. They activate fat cells to produce more proinflammatory factors. They interfere with insulin signaling, causing insulin resistance. They even enter the brain."

Husam Ghanim, Ph.D., research associate, is first author on the study.

The good news, said Dandona, is that, based on these findings, the status of mononuclear cells from one blood sample could serve as an easy early-warning system for the risk of developing insulin resistance and circulatory problems.

The research was conducted using fasting blood samples from 16 normal-weight subjects with an average body mass index (BMI) of 22.6 and from 16 obese subjects with an average BMI of 40. All participants had similar glucose levels and were taking no anti-inflammatory medication. The research was conducted at the Diabetes-Endocrinology Center of Western New York located in Kaleida Health's Milliard Fillmore-Gates Hospital.

Mononuclear cells were isolated, and proinflammatory and anti-inflammatory factors within the nucleus and the cell were assayed. The researchers also calculated an insulin-resistance index for each participant, using a standard formula.

Results showed that measures of proinflammatory factors were significantly higher in blood samples from obese subjects than the average weight subjects, while levels of factors that normally inhibit inflammation were significantly lower.

"This proinflammatory state may contribute to insulin resistance," said Dandona, "because the cytokines produced may interfere with insulin action." The index of insulin resistance in the obese subjects was nearly three times higher, on average, than that of the normal subjects, findings showed.

To remedy the inflammation, persons must either change their diet or take medication or both, Dandona said. His laboratory currently is conducting studies with obese subjects to determine how much these remedies are able to reduce cellular inflammation.

In addition to Dandona, UB Distinguished Professor in the Department of Medicine, UB School of Medicine and Biomedical Sciences, and Ghanim, researchers involved in the study, all from the Division of Endocrinology, Diabetes and Metabolism, were Ahmad Aljada, Ph.D., Deborah Hofmeyer, Tufail Syed, M.D., and Priya Mohanty, M.D.