Diabetes Medications Don't Lower Inflammation
TUESDAY Sept. 15, 2009 -- In people with newly diagnosed type 2 diabetes, the glucose-lowering medications metformin and insulin don't appear to reduce the inflammation associated with heart disease, new research suggests.
Even though these medications helped reduce glucose levels, the researchers found they didn't affect inflammatory markers any more than a placebo drug did, according to a study published in the Sept. 16 issue of the Journal of the American Medical Association.
"Heart disease is one of the many co-morbidities associated with diabetes," explained study author Dr. Aruna Pradhan, an assistant professor at the Harvard Medical School and Brigham and Women's Hospital in Boston, and a cardiologist at the VA Boston Medical Center. "We thought by lowering glucose levels that we would also address inflammation. But, we found that going lower in glucose levels doesn't impact inflammation, which is a risk factor for heart disease."
This study comes on the heels of other recent studies on diabetes and cardiovascular disease. Some suggested that intensive glucose control couldn't affect heart disease risk, while a recent meta-analysis suggests that good blood sugar levels could reduce death from heart attack, according to background information in Pradhan's study.
Almost 24 million Americans have diabetes, mostly type 2 diabetes, according to the American Diabetes Association. Risk factors for developing the disease include being overweight and being over 40, though younger and thinner people can also develop the disease. In type 2 diabetes, the body either doesn't produce enough insulin or can't use insulin effectively.
The current study included 500 men and women with type 2 diabetes diagnosed two years earlier on average. Slightly more women than men were included, and most of the study volunteers had a body-mass index above 30, which is considered obese. The majority of the study participants were white, and about one-quarter of the group were smokers.
The volunteers were randomized into one of four groups: placebo alone, placebo plus insulin glargine (Lantus), metformin (an oral anti-diabetes medication) alone or metformin plus insulin glargine. Study volunteers also received advice on diet and weight.
Overall, the volunteers lost an average of 3.2 pounds during the 14-week study, except for the insulin and placebo group.
As for markers of inflammation, the researchers found reductions in inflammation (as measured through levels of C-reactive protein, IL-6 and tumor necrosis factor receptor 2) for all of the groups. The insulin-plus-placebo group, however, had the smallest reduction in inflammatory markers. For example, C-reactive protein levels went down in the placebo group by 19 percent, in the metformin group by 16 percent and the metformin and insulin group by 20 percent. However, the insulin plus placebo group went down just 3 percent.
Pradhan said the researchers adjusted the data to account for the weight loss, and still found a similar effect. She said it may be that the weight changes affected the distribution of fat, and that abdominal fat tends to have more of an effect on inflammation.
"While these two agents didn't lower inflammation [any more than the placebo], they did lower glucose levels and are excellent drugs for preventing microvascular outcomes, like eye and kidney diseases," said Pradhan. The findings also confirm that diet and exercise can affect inflammation levels, she added.
"While this is a well-conducted study, there are no big surprises here," said Dr. Vivian Fonseca, chief of endocrinology at Scott & White Clinic in Temple, Tex., and Texas A&M Health Sciences Center, College Station. "There are many drugs that benefit people and reduce cardiovascular risk without decreasing inflammation, and there are drugs that reduce inflammation that have sometimes killed people from cardiovascular disease."
"We're trying to look at this problem the other way," said Fonseca. She and other researchers across the country will test an anti-inflammatory medication, salsalate, to see if lowering inflammation directly can have an impact on blood glucose levels.
Posted: September 2009