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Inflammation, Insulin Resistance and Weight Issues

The medical jury is still out when it comes to the precise role of excess weight or obesity in the onset of inflammation. But this latter condition is increasingly being implicated in such disorders as heart disease and pre- and type 2 diabetes, all of which are often closely linked with insulin resistance and weight issues in both sexes. Women with polycystic ovarian syndrome (PCOS), a leading cause of infertility, are also thought to be vulnerable.

Inflammation is part of the body's immune system, which triggers a defense response to harmful stimuli. The body reacts to injury by sending specialized blood cells to damaged areas where they attack "invaders," like renegade molecules called "free radicals," and clean up dead and dying cells.

Blood Glucose Monitor Insulin ResistanceIn the case of inflammation and weight issues, the "invader" may be excess levels of insulin caused by the imbalance of blood glucose and insulin called insulin resistance.

Inflammation can take an external form like the reddened, tender skin which draws attention to a splinter in your finger. Or it can be an unseen, internal process in response to something harmful and long-term like high blood pressure, which can stem from excess weight or obesity.

To combat internal harm, inflammation produces C-reactive protein (CRP), which, unfortunately, can damage the arteries by helping to form plaque while attempting to tackle a condition like high blood pressure.

Plaque is a substance that attaches itself to artery walls, damaging those walls and seriously impairing blood flow, which can lead to a heart attack or stroke. A blood test measures CRP levels and the higher that level is, the more at risk you are from cardiovascular disease. There's contradictory evidence, however, about whether CRP levels and insulin resistance are closely linked.

Research about inflammation is often cutting-edge material that still needs ample verification. But scientists are gathering data that inflammation can precede and predict pre- and type 2 diabetes - conditions which people suffering from excess weight or obesity are prone to developing. Previous research had already linked inflammation to heart disease and obesity.

Pre- and type 2 diabetes are characterized by high blood-sugar concentrations that result from defects in the body's use or production of insulin. With pre-diabetes, the levels of glucose and insulin are higher than normal but not elevated enough for a diagnosis of type 2, which is why pre-diabetes is reversible via weight loss as a result of a balanced, nutritious diet and regular exercise.

If neglected, however, pre-diabetes may lead to full-blown type 2 diabetes, which can only be managed in the vast majority of cases and often requires daily injections of insulin. Type 2 diabetes, itself, is a severely increased risk factor for serious complications like heart and kidney disease, declining vision and blindness and the need for amputation.

Normally, insulin guides sugar - the body's basic fuel for energy - from the bloodstream into cells via the cells' walls. But unbalanced insulin levels, due to insulin insensitivity in the cell wall caused by insulin resistance, lead to high, unhealthy concentrations of blood sugar because the latter has been "refused entry" into the cell for conversion into energy.

Scientists on the frontier of inflammation research are testing people's blood samples not only for insulin and glucose levels but also for a variety of compounds associated with inflammation. Some of these, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), are cytokines - chemical signals that the immune system uses to marshal inflammatory activity.

Others, such as so-called acute-phase proteins made by the liver, rise in response to increased cytokine concentrations. These proteins don't contribute directly to inflammation but, because they remain detectable in blood longer than cytokines do, they are a convenient measure of it.

Microscopic view of fibers Insulite ResearchThe concentrations of cytokines and acute-phase proteins, such as C-reactive protein (CRP) rise at least a hundredfold when a person contracts an infection.

By contrast, in most studies linking inflammation to heart disease, these inflammation markers reach only perhaps twice-normal amounts. So it's not clear whether at such low concentrations the cytokines trigger swelling or other inflammatory responses.

Most of the evidence comes from analyses of blood samples and data collected in studies that have followed the health of large numbers of people over several years. All these investigations have used statistical techniques to take into account various factors, such as obesity, that might confound their results.

Recent support for the CRP-Diabetes link came from a study presented in the October 2001 edition of Diabetes journal. Researchers tracked 5,888 U.S. residents without Diabetes, 65 or older, who got their health care from the Kaiser Permanente health maintenance organization. Among the quarter of people with the highest CRP blood concentrations at the beginning of the study, twice as many had been diagnosed with Diabetes after 3 to 4 years, compared with the quarter of people with the lowest CRP concentrations.

Other researchers have looked at both CRP and cytokines. As part of a long-running national study, researchers at Brigham and Women's Hospital in Boston compared the medical histories of 188 middle-aged women who had Diabetes with records on 362 women of similar age and weight who didn't have the condition. The quarter of women who had the highest CRP concentrations early in the study were four times as likely to develop Diabetes as the 25% of women with the lowest CRP concentrations.

Reverse PCOS and InflammationAlso, women with the highest IL-6 concentrations were more than twice as likely to develop Diabetes as the women with the lowest IL-6 concentrations. Finally, those with the highest concentrations of both IL-6 and CRP were six times as likely to develop the disease over the course of the study as women with low concentrations of the two compounds.

So far, there are no epidemiological studies that can prove inflammation causes Diabetes and it's possible that some unknown factor pre-disposes people to the pre- and type 2 varieties.

One candidate could be obesity. Many women with inflammation-linked polycystic ovarian syndrome (PCOS), for example, are overweight or obese, though they do not have a monopoly of this condition. Females of normal weight can suffer from PCOS and so, too, do lean women. But fat cells are known to produce cytokines, with CRP typically elevated in people who are overweight.

Some studies suggest inflammation causes insulin resistance itself. Animals with infections and those with cancer have high concentrations of cytokines, with scientists detecting increased Insulin Resistance in these animals.

Researchers are now examining whether animals without underlying disease but with altered amounts of inflammatory cytokines are vulnerable to Diabetes. For instance, mice lacking the gene for the cytokine TNF-alpha are less likely to develop obesity-linked insulin resistance than are mice with that gene. Recently scientists have shown that TNF-alpha blocks insulin from getting into cells.

The general picture is still murky right now. But it's likely to become much clearer in the not-too-distant future. Nevertheless, men and women who suffer from excess weight or obesity need to be mindful of how vulnerable their condition can make them to inflammation-linked disorders.

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Article by Dr. Sheri Colberg, Phd, FACSM

"The United States is experiencing an epidemic of obesity. Thirty-four percent of adults are overweight and an additional 30% are obese. Thus, 2 of every 3 Americans have an unhealthy body weight. Obesity contributes to over 300,000 deaths per year, principally through its association with cardiovascular disease, type 2 diabetes, and several cancers. Obesity currently is the second leading cause of preventable death and will soon surpass cigarette smoking, the leading cause. Health economists estimate that obesity costs our nation approximately $100 billion a year. And these figures say nothing about the personal suffering of those affected by obesity."
Testimony of the North American Association for the Study of Obesity (NAASO) before the U.S. House of Representatives Committee on Government Reform, Subcommittee on Human Rights and Wellness, 9.15.2004 (.PDF)

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