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The medical profession is still debating and exploring the precise role of inflammation in the onset of reversible Pre-Diabetes, which, if left unchecked, can develop into the Type 2 variety.

The latest signs, however, are that inflammation could be a crucial factor in the onset of Pre-Diabetes.

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 the renegade molecules called "free radicals" and clean up dead and dying cells.

Blood Glucose Monitor DiabetesIn the case of inflammation and Pre-Diabetes, the "invader" is thought to be excess levels of insulin, which can be 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 like high blood pressure.

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 long-term 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 precedes and predicts Pre- and Type 2 Diabetes. Previous research had already linked inflammation to heart disease and obesity, which are both common in people with Diabetes.

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.

Normally, insulin guides sugar, the body's basic fuel, from the bloodstream into cells. But unbalanced insulin levels, which can be caused by Insulin Resistance, lead to unhealthily high concentrations of blood sugar. These, in turn, can lead to heart disease, blindness, kidney disease and circulation problems that may require amputation.

Scientists on the frontier of Diabetes 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.

Reverse Pre DiabetesThe 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 Diabetes and 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.

Grandmother and Granddaughter: Reverse Pre DiabetesAlso, 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. Fat cells are known to produce cytokines, with CRP typically elevated in people who are overweight.

Some studies suggest inflammation causes Insulin Resistance. 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.


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"Simply losing 5-7% of your body fat (typically 10-15 pounds) and increasing your physical activity by taking a brisk walk 4-5 times a week can reduce your risk of developing Type II Diabetes by almost 60%."
Diabetes Prevention Program study 2001, study funded by the National Institute of Child Health and Human Development, et al.
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Our results support the view that improving insulin resistance may be crucial in the prevention of both type 2 diabetes and premature cardiovascular disease in this at-risk subpopulation of Hispanic youth."
Cruz ML, Weigensberg MJ, Huang TT, Ball G, Shaibi GQ, Goran MI.,J Clin Endocrinol Metab. 2004 Jan;89(1):108-13.
Article by Dr. Sheri Colberg, Phd, FACSM
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