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[IP] RE: Complications

I read Jacob Chojnacki's post on complications and thought it posed an
interesting question.  Its useful to look at what research has revealed on the
subject.  Although some of us question whether spending $165 million on a
study to "prove" that better control reduces complications couldn't have been
better spent on cure or treatment-related research (after all, if we could
always maintain good control, it would be similar to not being a diabetic, so,
isn't it common sense that it would reduce complications?), the much-heralded
DCCT proved that good glycemic control dramatically reduced or delayed the
incidence of diabetes-related complications.  The results were as follows:

76% reduced risk of eye disease
50% reduced risk of kidney disease
60% reduced risk of nerve disease

(If readers have never actually seen the DCCT results, the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK), which is part of the
National Institutes of Health, provides a link to the results at the following


The fact remains that while good glycemic control dramatically reduces the
risk of complications, having DM still results in a statistically higher risk
of encountering kidney disease, retinopathy, neuropathy, and cardiovascular
disease than the general population, even with good control.  Which is what
makes Jacob's question so interesting.  However, its also true that good
glycemic control is the best tool we available to minimize the impact of DM
and related complications, and I believe pumps are an excellent (if less than
perfect) tool to do that.

Countdown magazine (published by the Juvenile Diabetes Foundation) had a very
intersing article on research progress last summer, which addressed a lot of
Jason's question.  In the interest of keeping this post less than a mile long,
I've included a relevant excerpt, but the entire article can be viewed at the
following link


Happy reading!
Scott Strumello

Age 33, Type 1 for the past 26 years (and old enough to remember 4+ACs),
hopefully soon to be pumping


The Diabetes Research Pipeline, by Robert S. Dinsmoor.
(from Summer 2001 Countdown)
What Causes Diabetes-related Complications and How Can We Prevent Them? 

At least as early as the 1930s, shortly after the discovery of insulin,
diabetes researchers debated whether hyperglycemia (high blood sugar levels)
was the driving force behind the development of diabetes-related
complications, according to David M. Nathan, M.D., director of the Diabetes
Center at Massachusetts General Hospital in Boston. That debate continued for
nearly five decades.

"If you look back at the literature from the 1960s and 1970s, there was an
enormous debate going on, with a whole series of editorials, letters, and
special articles in the New England Journal of Medicine. Two distinct sides
were arguing whether glucose control was the issue," he recalls. "It was a lot
of hot air, because we didn+IBk-t have the means to adequately measure or
control blood glucose levels at the time, nor did we have methods for
objectively measuring the development of, for example, eye disease or nerve
disease. As much as people yelled back and forth, the truth is they just
didn+IBk-t know."

In the ensuing decades, a lot changed. In the early 1980s, the hemoglobin Alc
(HbA1c) test came into widespread use and was shown to be a reliable and
useful indication of long-term blood glucose control. Meanwhile, more and more
patients with diabetes began to monitor their own blood glucose levels.
Increasing numbers of patients began using insulin pumps and newly designed
multiple-injection regimens to achieve tight control over blood glucose
levels. Researchers developed ways to objectively measure and quantify varying
degrees of diabetes-related complications. At the same time, there was a shift
toward evidence-based medicine+IBQ-that is, making treatment decisions based on
the results of scientific studies rather than tradition or educated guessing.

According to Dr. Nathan, all these developments set the stage for the landmark
Diabetes Control and Complications Trial (DCCT). This very rigorously designed
study, the results of which were published in 1993, proved beyond a shadow of
a doubt that tight blood glucose control could dramatically delay the
development of diabetic eye disease (retinopathy), diabetic kidney disease
(nephropathy), and diabetic nerve disease (neuropathy) in most people with
Type 1 diabetes. 

"The major remaining question is, Can we make intensive insulin therapy more
user-friendly, more accessible, easier, and less burdensome to the patient?"
Dr. Nathan says. 

Simplifying intensive insulin therapy is proving to be no easy task. Even with
new tools and technologies, researchers and manufacturers have made only
modest strides in making blood glucose control easier and more precise. Two
fast-acting insulin analogs+IBQ-insulin lispro (Humalog) and insulin aspart
(Novolog)+IBQ-as well as a long-acting insulin analog+IBQ-insulin glargine
(Lantus)+IBQ-may well prove effective in fine-tuning blood glucose control.
Additionally, at least two manufacturers are working on inhaled insulin
products to make insulin delivery more comfortable for the patient. 

Technologies using minimally invasive, continuous glucose monitoring of
interstitial fluid (the glucose-containing fluid under the skin) may
eventually provide better information for improving blood glucose control.
Ultimately, this type of technology may allow for "closed-loop" insulin
delivery, whereby an insulin pump can continually change its insulin output
based on moment-to-moment changes in blood glucose levels. 

"Some of these continuous monitors are in use now and I think they're going to
revolutionize therapy," says Dr. Eisenbarth.

In the early 1980s, researchers began testing certain drugs called
aldose-reductase inhibitors in patients with diabetic neuropathy.
Aldose-reductase is an enzyme that acts on glucose to produce sorbitol;
another enzyme called L-iditol dehydrogenase acts on sorbitol to produce the
sugar fructose. When blood glucose levels are high, excessive amounts of
sorbitol and fructose are produced; this excess is believed to contribute to
diabetic complications, especially neuropathy. Aldose-reductase inhibitors,
designed to block this biochemical pathway, have shown promise in laboratory
animals but not in human clinical trials. In the early 1980s, researchers
discovered other potential contributing pathways, involving another enzyme,
protein kinase C-beta (or PKC-beta), and toxic substances called advanced
glycation endproducts (or AGEs), which are now believed to play a key role in
various diabetic complications.

In the late 1990s, scientists began to study superoxide (a reactive form of
oxygen) produced by the mitochondria. Researchers hypothesized that an
overproduction of superoxide was somehow connected to diabetes-related
complications. The mitochondria is essentially the cell+IBk-s "powerhouse,"
converting glucose and fat into the energy-yielding molecules needed for cells
to operate. In response to excess glucose that occurs in diabetes, however,
the mitochondria malfunctions and overproduces superoxide, which in turn gives
rise to other reactive species that damage cells. The process sets off a
destructive sequence of events inside otherwise healthy cells. 

In a study recently reported in Nature, Michael Brownlee, M.D., Anita and Jack
Saltz Professor of Diabetes Research at the Albert Einstein College of
Medicine in New York, and an international cadre of colleagues were able to
show that the overproduction of superoxide appears to be the "master switch"
that initiates all hyperglycemia-induced biochemical pathways previously
thought to act independently of each other.

"A naturally occurring enzyme called superoxide dismutase normally rids the
body of superoxide. Using a new technology called combinatorial chemistry,
several small companies are testing small-molecule agents called superoxide
dismutase mimetics, which a person could swallow. The agents would act
identically to the enzyme inside hyperglycemic cells," Dr. Brownlee explains.
"I think this is going to be a very central part of the treatment of
complications in the next 5 or 10 years."


Date: Wed, 03 Apr 2002 22:23:08 -0600
From: Jacob Chojnacki <email @ redacted>
Subject: [IP] Complications

Ok, Hi everyone.  I got a question.  I have had diabetes for 14 years and
I'm 24 years old.  I have read so many different studies and stories about
complications from diabetes.  I want to know IF WE CONTROL OUR BLOOD SUGARS


i have been pumping for the last year and my A1C's are at 6.3, which i think
is great.  I am starting an exercise program and nutrition.   I just want some
kind of hope that i'm not going to be stuck with failed kidneys no matter how
hard I work at this.....


jacob Chojnacki
dx 14 years.... 1 year pumping MM508
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