Health: Diabetes A Slow, Savage Killer

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 superglue.” 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.