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In 1999, the first association between markers of inflammation and the subsequent development of type 2 diabetes was reported. Today, researchers are positing a definitive link between the two and suggesting that treatments to reduce inflammation might be a means of preventing or forestalling illness.
What Is Inflammation?
At a press conference during the June 2002 American Diabetes Association Scientific Sessions in San Francisco, California, a panel of researchers began by defining inflammation as the way the body normally responds to injury.
Inflammation is a protective reaction by the body to injury, irritation or infection. The inflammation process occurs, for instance, when you bump your head or scratch your arm. You get swelling and redness because specialized blood cells are sent to the area of injury to destroy and clean up damaged cells.
However, when the immune system malfunctions, the inflammation process itself damages healthy tissue.
An earlier link between inflammation and heart disease was made when doctors found higher levels of inflammation markers in the blood of people with heart disease. They then discovered that such markers could predict a heart attack. Higher levels of those same markers have now been found in people with diabetes and those at risk for diabetes.
What Are the Markers?
One inflammation marker, known as C-reactive protein (CRP), appears to be elevated in the presence of heart disease, diabetes and obesity.
Vivian Fonseca, MD, professor of medicine at Tulane University Health Sciences Center in New Orleans, Louisiana, says: "It is possible that if you have excessive fat, substances secreted from fat stimulate markers of inflammation. So inflammation may be the common link for developing insulin resistance, diabetes and heart disease, making it very attractive to monitor and treat CRP levels."
In data collected from a study funded by the National Institutes of Health, more than 10,000 people who did not have diabetes were followed with blood sampling for nine years. According to Bruce Duncan, MD, PhD, associate professor in the School of Medicine of the Federal University of Rio Grande do Sul, individuals who had high levels of inflammation - especially sialic acid - were at 20 to 60 percent higher risk for developing diabetes than those with lower levels.
"We have here now a study that demonstrates that markers of inflammation can predict the development of diabetes," says Duncan. "The question is no longer 'Does this association exist?' but now 'Why does it exist?' "
In a separate study conducted in Hong Kong, researchers point out that a high CRP level was an "independent predictor" for the development of kidney disease in people with diabetes.
Other inflammation markers include plasminogen activator inhibitor-1 (PAI-1) and nuclear factor kappaB (NfkappaB).
So What Can You Do?
Researchers at Kuwait University in Kuwait found that people with diabetes whose levels of CRP markers were in the highest 20th percentile were four times more likely to suffer from cardiovascular disease than those who measured in the lowest 20th percentile. Nabilla Abdella, MB, CHP, FRCP, professor of medicine at Kuwait University, says people with diabetes who have high levels of CRP markers need to more tightly regulate blood pressure and cholesterol as well as blood glucose.
Paresh Dandona, FRCP, MD, PhD, head of the division of endocrinology, diabetes and metabolism at the State University of New York at Buffalo, suggests that food intake leads to an inflammatory state and that people who are obese are at a constant risk.
Dandona argues that "healthy living" is the best way to keep inflammation markers down.
"I personally think that any attempt to restrict caloric intake in a nation that overconsumes calories by the ton is commendable Ã‰ If people lose weight, these markers come down dramatically."
However, Dandona acknowledges that losing weight is difficult. That being the case, he recommends the use of drugs to aid in the process.
Studies have demonstrated that type 2 diabetes drugs in the thiazolidinedione class ("TZDs," or "glitazones"), such as Avandia, have anti-inflammatory benefits.
In a recent study, inflammation markers fell by 20 to 40 percent after six weeks in 11 people who were taking 4 mg per day of rosiglitazone (Avandia), according to Dandona.
"This leads us to speculate that patients treated with [Avandia] might not develop atherosclerosis [narrowing of the arteries] at the high rate usually seen in diabetes," he says, adding that such treatment of those at risk for diabetes might help prevent the disease itself.
Although Avandia's counterpart Actos (pioglitazone) was not used in the study, Dandona predicts that it would have the same effect.
Statins, which are used to reduce high cholesterol levels, have also been found to reduce inflammation markers.
A study of adults in Saskatchewan with type 2 diabetes found that statin use was associated with a 10-month delay in the need to start insulin treatment, according to Jeffery A. Johnson, PhD, associate professor of public health sciences at the University of Alberta, Canada. He suggests that the anti-inflammatory action of statins might decrease insulin resistance.
Johnson recommends evaluating the potential of statins to delay the onset of diabetes in high-risk individuals.
Clinical adviser's note: Along with the exciting news about the anti-inflammatory properties of the TZDs and the statins, attention has also been rekindled regarding that good old standby aspirin. In addition to aspirin's anti-platelet activity, which makes it useful as a daily preventive therapy for reducing cardiac risk, aspirin's anti-inflammatory effects may reduce cardiac risk even further than the anti-clotting action alone.
Also stay tuned for new guidelines regarding broad testing for CRP, one of many chemicals that increase if inflammation is present. Who should be tested? That is the question that an expert panel is contemplating. The good news is that the CRP test is relatively inexpensive.
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Inflammation Marker Associated With Previous Gestational Diabetes Is Linked to Type 2
Increased levels of the inflammation marker total sialic acid (TSA) are associated with previous gestational diabetes, say researchers in the United Kingdom and Brazil.
"Gestational diabetes predicts type 2 diabetes and may be part of this syndrome," write the researchers.
Women who had a history of gestational diabetes were observed against a random sample of 46 women with no history of gestational diabetes. The average TSA was 71.8 mg/dl higher in the women who had previous gestational diabetes. After adjustment for body mass index, fasting insulin sensitivity and number of years spent in school, TSA was 4 mg/dl higher in women who had previous gestational diabetes.
-Diabetes Care, August 2002
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