INFLAMMATION, INSULIN RESISTANCE AND PRE-DIABETES
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.
 In 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.
 The 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.
 Also, 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.
Click here to read about Diabetes
and Glycemic Index (GI).
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