TIME: Almanac 1993/TIME Almanac 1993.iso/time/112690/1126130.000

Text File | 1992-08-28 | 17.0 KB | 337 lines

                                                                                HEALTH, Page 52

Special Report: Diabetes

A Slow, Savage Killer


Scientists are battling high blood sugar, the overlooked
affliction that strikes millions

By J. MADELEINE NASH/CHICAGO


    Among dread diseases, from multiple sclerosis and cancer to
Alzheimer's and AIDS, diabetes might appear to be one of the
least threatening. If not quite perceived as conquered, it is
widely viewed as a manageable, albeit serious, affliction.
People with diabetes talk about living with their illness, not
dying from it. To prove the point, they resolutely lead active
and productive lives. Later, however, many will discover that
this insidious disease has mocked their efforts to control it.
Like a dormant volcano, diabetes can feign slumber for many
years, only to erupt with sudden savagery.

    Consider the case of Arthur Hettler III, a once energetic
high school principal from San Antonio. At first Hettler
thought he had just a mild case of diabetes. He required no
medication to control the excess blood sugar caused by the
disease; instead, he watched his diet as carefully as he could.
Then, two summers ago, Hettler strolled barefoot across some
sun-scorched pavement and blistered his feet. Ominously, the
blisters on his right foot refused to heal. A few months later
the foot was so badly infected that it had to be amputated.
Shortly before Christmas, Hettler, 47, suffered a paralyzing
stroke. The infection and the stroke were complications
resulting directly from the slow progression of diabetes. "The
disease," observes Hettler, "can really creep up on you."

    And it has crept up on an estimated 100 million people
worldwide, among them actress Mary Tyler Moore, jazz musician
Dizzy Gillespie and singer Ella Fitzgerald. Because the initial
symptoms (fatigue, frequent urination) are usually mild, half
the 12 million Americans with diabetes do not realize they have
it. Even after diagnosis, many patients fail to take diabetes
as seriously as they should. "At first, everything goes along
fine," sighs June Howe, a patient at Boston's Joslin Diabetes
Center. "You don't realize that later on problems will set in."

    That is an understatement. Diabetes more than doubles the
risk of a disabling heart attack or stroke. It is the leading
cause of blindness in adults and accounts for a third of all
cases of kidney failure. Only traumatic injuries are
responsible for more amputations. Altogether, the complications
have made diabetes the seventh leading cause of death in the
U.S.

    Fortunately, as awareness grows that diabetes is a major
killer, some discoveries in the field are giving new hope to
its victims. Scientists are beginning to understand what causes
diabetes and how to slow its progress. In fact, researchers are
increasingly optimistic about developing drug treatments that
may stop the affliction cold in many cases.

    Diabetes results from an inability to produce or respond
properly to insulin, the hormone produced in the pancreas that
enables muscle, fat and liver cells to absorb sugar in the form
of glucose, an essential fuel in the body. Inside the cells,
glucose that is not immediately burned for energy is normally
stored for future use. But when the body fails to produce
insulin, excess glucose accumulates in the bloodstream instead
of being stored, and is cleared by the kidney for excretion in
urine. With the onset of diabetes, the loss of so many calories
through the urine typically causes a loss of weight. In extreme
cases, sugar-starved cells, deprived of their preferred fuel,
switch to burning fatty acids, a process that can poison the
bloodstream with toxic byproducts. In Type I diabetes, which
chiefly strikes in childhood, the body completely loses its
ability to produce insulin. In Type II diabetes, common among
adults, the body continues to produce insulin, but not in
sufficient quantities to prevent the blood's sugar level from
soaring.

    Before insulin injections became available in the 1920s,
diabetes in its severest form invariably proved fatal. Now
patients can often look forward to normal life spans. "The good
news," notes diabetes expert Dr. Frank Vinicor of the Centers
for Disease Control, "is that people with diabetes are living
longer. The bad news is that they are developing chronic
complications." In many patients, the complications are so
benign as to go unnoticed; in others, they can be devastating.

    Diabetes usually damages cells in the retina and lens of the
eye. It can also destroy the filtration system of the kidney,
accelerate the process of atherosclerosis and kill nerves. With
deadened nerves, feet lose sensation, making them injury prone.
Because blood flow is impeded, wounds heal more slowly, and
infections get out of hand. The combination of nerve and
circulatory damage causes many diabetic men to become impotent.
In pregnant women diabetes has been linked to multiple
problems, from congenital defects to stillbirths.

    "People think you just take your insulin and you're fine,"
says Chicago attorney Marjorie Hunter. She knows how wrong that
can be. Diagnosed as having diabetes at 14, Hunter has waged
a long battle with a series of complications that would have
overwhelmed Job. Her ordeal began while she was in the first
year of law school. "My feet," she recalls, "turned into a
tangle of pain." It was a distress signal relayed by nerves
that were inflamed and dying. Eventually her feet became numb.
In April 1985, shortly before she turned 29, Hunter was told
she had end-stage kidney disease. In August, she recalls, "I
woke up and couldn't see the numbers displayed on my alarm
clock." To cap things off, that November she had a heart
attack. Today Hunter remains partially blind, wearing
telescopic eyeglasses that, she jokes, make her look like a
punk rocker. But thanks to kidney and pancreas transplants, the
deterioration in her health has halted, and insulin shots are
no longer necessary. "I call myself an ex-diabetic," she grins.


    How does diabetes create havoc in the body? While people
without the disease keep blood sugar within a narrow range (60
mg to 120 mg per deciliter of blood), those with diabetes
frequently boast levels three times as high. Just how excess
sugar causes damage remains a topic of debate. One plausible
mechanism has been suggested by Dr. Michael Brownlee, of the
Albert Einstein College of Medicine in New York City. Glucose,
Brownlee observes, is chemically active, combining with
proteins in the blood and blood-vessel walls. Over time, these
sticky fragments aggregate to form what Brownlee calls
"biological super glue." Like a splinter lodged in a foot, this
superglue is a source of constant irritation, which signifies,
to the body, damage in need of repair. The disastrous result:
a spurt of new growth that thickens the walls of capillaries
and arteries, constricts blood flow and damages critical
organs.

    Diabetic complications have also been linked to elevated
levels of sorbitol, a sugary alcohol. Even in the absence of
insulin, certain cells, such as those in the lens of the eye,
continue to absorb glucose. But without insulin, glucose cannot
be processed in the usual way; the cell instead converts it to
sorbitol. The abnormal accumulation of sorbitol causes cell
membranes to swell and leak. It also interferes with vital
biochemical processes.

    Even after complications develop, the prognosis is not
unrelentingly grim. Laser surgery is saving eyesight. Bypass
surgery is salvaging hearts and feet. Dialysis machines and
organ transplants are pinch-hitting for nonfunctioning kidneys.
Most important, insulin pumps and home-monitoring kits are
enabling diabetics to control their blood-sugar levels more
precisely than ever before. With good control, diabetic women,
once cautioned not to have children, are now delivering healthy
babies. Says Dr. Gordon Weir, medical director of the Joslin
Diabetes Center: "Patients are finally tuning in to the fact
that high blood sugar is serious business."

    Because their disease is more acute, Type I diabetics have
been particularly motivated to adopt strict treatment regimens.
"The long-term complications of this disease scare the hell out
of me," declares Ken McDonald, a 45-year-old computer engineer
from Wellesley, Mass. Instead of sticking with the traditional
treatment of two insulin shots a day, he began what is called
"intensive therapy" four years ago. In that approach, he
receives insulin more or less continuously, as needed. Around
his waist McDonald wears an insulin pump the size of a pager,
which infuses the hormone through a slender needle positioned
just below his skin. Anticipating meals, McDonald can increase
the amount of insulin he receives by dialing in a number.
McDonald carries with him a finger pricker and a pocket-size
glucose monitoring machine. Eight times a day he checks the
level of glucose in his blood and adjusts his insulin pump
accordingly.

    Even with all these tools, McDonald can only approximate
what a nondiabetic pancreas does naturally. A pinkish-yellow
organ the size of a banana, the pancreas contains millions of
specialized cells that continuously manufacture insulin and
package it in microscopic granules. In response to rising
blood-glucose levels, these tiny factories release the granules
into the bloodstream. As glucose levels fall, the insulin
release tapers off, thus preventing blood sugar from plummeting
to dangerous levels and starving the brain of fuel -- and
consciousness. Fortunately, this life-threatening condition,
known as hypoglycemia, can easily be countered by eating or
drinking something sweet.

    Intensive insulin therapy may prevent or delay
complications, but it also sharply increases the likelihood of
hypoglycemia. For this reason, in 1982 the National Institutes
of Health launched a clinical trial to assess the connection
between blood-sugar levels and the development of
complications. Half the 1,441 volunteers are following the
standard policy of two insulin shots a day. The rest belong to
an intensive-therapy group that tries to keep blood sugar as
close to normal as possible. Some participants, like Ken
McDonald, are using insulin pumps. Others inject themselves
with insulin four times a day. The results, scheduled for
release in 1993, should determine whether or not the benefits
of intensive therapy outweigh the risks. Cautions Dr. Saul
Genuth of the Mount Sinai Medical Center in Cleveland:
"Everyone's hunch is that it will be beneficial. But hunches
don't count in medicine."

    For years medical researchers have dreamed of not just
controlling diabetes but preventing it. For Type I diabetes
that goal seems tantalizingly close. Like multiple sclerosis
and rheumatoid arthritis, Type I diabetes is known to be an
autoimmune disorder. What this means is that the
insulin-producing areas of the pancreas are attacked by the very
cells charged with protecting the body from viruses and other
invaders.

    An autoimmune attack is analogous to the rejection process
that occurs in patients who receive transplanted organs. To
prevent rejection, transplant recipients are routinely given
cyclosporine, a powerful drug that dampens the immune system
and prevents it from attacking the foreign tissue.
Intriguingly, clinical trials in the U.S., Canada and France
have shown that cyclosporine, when given to people with Type
I diabetes, can turn off the autoimmune attack. Cyclosporine is
an extremely toxic drug and, in most cases, a very poor trade
for insulin. But the clear demonstration that diabetes can be
stopped has stirred excitement in the medical community.

    One sign that an autoimmune attack has begun is the
appearance in the bloodstream of antibodies to the pancreatic
cells and, later, to insulin itself. For nine years a Joslin
Center research team led by immunologist Dr. George Eisenbarth
has been tracking the appearance of these antibodies in 10,000
close relatives of Type I diabetics. It is now possible for the
Joslin team to predict which otherwise symptomless relatives
are likely to develop the disease in three years' time. Last
May the Joslin and two other medical centers launched a program
to treat identified potential diabetics with an antirejection
drug less toxic than cyclosporine. The ambitious goal: to
block the onset of disease. In the future, researchers imagine
launching molecular missiles that will seek out and destroy the
rogue immune cells that cause Type I diabetes. They also
envision a vaccine that will rally the immune system against
the traitors in its ranks. "Intellectually," says immunologist
Dr. Terry Strom of Boston's Beth Israel Hospital, "we are on
the right track."

    But Type I diabetes affects only about 10% of the total
diabetic population. The majority of people with diabetes, like
former high school principal Hettler, have the Type II form of
the disease. Paradoxically, the fact that Type II diabetes is
less severe has made it more difficult to handle. Until
recently, many physicians believed Type II was largely
innocuous and counseled patients not to worry. True, many Type
II diabetics never require insulin and get by on pills that
stimulate the pancreas to produce the hormone. Over time,
however, they develop the same terrible complications as their
Type I counterparts. University of Michigan's Dr. Stefan Fajans
vividly remembers the autoworker he diagnosed with Type II
diabetes at age 41. Twenty years later the man was blind and
had had one leg amputated. He died a short time later of a
heart attack. "This form of diabetes," warns Dr. Fajans, "is
not a benign disease."

    In the U.S., 90% of those who develop Type II diabetes are
obese. The tendency of obesity to increase with age largely
explains why this disease attacks predominantly people over the
age of 40. In obese people, cells quickly become sated and
sluggish. They reduce their sensitivity to insulin and, thus,
their appetite for glucose. To compensate, the pancreas
heroically pumps out more and more insulin. Usually it is able
to keep up with the work load. As Dr. Jeffrey Flier, an
endocrinologist at Beth Israel Hospital, emphasizes, "Most
obese people do not have diabetes." In susceptible individuals,
however, obesity can overload the system, and insulin-producing
cells begin to stop functioning. One intriguing, if
controversial, hypothesis suggests that obese people may
produce large quantities of amylin, a protein made by the same
cells that secrete insulin. Some researchers believe that
amylin deposits in the pancreas contribute to diabetes by
interfering with the functioning of the organ.

    In the initial stages of the disease, Type II diabetics have
a chance to bring their blood sugar back to normal by dropping
a modest amount of weight. But not many succeed. Even more than
Type I, Type II diabetes appears to run in families. If both
parents develop the disease before middle adulthood, the chance
a child will contract it runs close to 80%. Diabetes is endemic
among many American Indian tribes, notably the Pima Indians of
southern Arizona, who have the highest incidence of Type II
diabetes in the world (50% of those over age 35).

    It is also alarmingly common among Hispanics. In some
neighborhoods of San Antonio, one person in five has diabetes.
The complications experienced by Hispanic diabetics are severe,
yet many cannot afford the equipment that would enable them to
keep track of their blood sugar. Often they are so badly
informed about their disease that they skrimp on the oral
medication or insulin shots they need to keep blood glucose in
the normal range. In the Rio Grande Valley of Texas, a large
health-promotion project, A Su Salud, has begun to spread the
word about diabetes on Spanish-language radio and television.

    Similar educational initiatives are needed across the U.S.
-- and around the world. Already, the Soviet Union has targeted
diabetes as one of its major medical problems. Even in Japan,
where diabetes remains relatively uncommon, a steady rise in
the number of cases has prompted concern about the rich diet
and lack of exercise that have accompanied economic success.


    Whether they suffer from Type I or Type II, diabetics must
be educated and motivated to manage their disease on a daily
basis. "Yet ironically," notes University of Vermont
endocrinologist Dr. Edward Horton, president of the American
Diabetes Association, "our health-care system does not pay for
education." That, experts agree, needs to change. As the U.S.
population ages rapidly, diabetes, which already costs the
nation $20 billion a year, is expected to become increasingly
common. And since rising affluence and obesity go hand in hand,
the disease can be expected to take root and flourish in
developing countries, where it is now rare. In the coming
years, every penny spent educating patients about this terrible
disease could help save health-care dollars and prevent
incalculable suffering.