An American Epidemic: Diabetes

Something terrible was happening to Yolanda Benitez's eyes. They were being poisoned; the fragile capillaries of the retina attacked from within and were leaking blood. The first symptoms were red lines, appearing vertically across her field of vision; the lines multiplied and merged into a haze that shut out light entirely. "Her blood vessels inside her eye were popping," says her daughter, Jannette Roman, a Chicago college student. Benitez, who was in her late 40s when the problem began four years ago, was a cleaning woman, but she's had to stop working. After five surgeries, she has regained vision in one eye, but the other is completely useless. A few weeks ago, awakening one night in a hotel bedroom, she walked into a door, setting off a paroxysm of pain and nausea that hasn't let up yet. And what caused this catastrophe was nothing as exotic as pesticides or emerging viruses. What was poisoning Benitez was sugar.

Benitez is a representative victim of what many public-health experts believe will be the next great lifestyle-disease epidemic to afflict the United States: diabetes. (Technically, type-2 diabetes, which accounts for 90 to 95 percent of all cases.) At five feet one and 140 pounds, Benitez is overweight; 85 percent of all diabetes sufferers are overweight or obese. She was born and reared in Mexico; Hispanics and blacks are more likely to contract diabetes than Caucasians. As the American population becomes increasingly nonwhite and obese, the disease is rapidly spreading. A study by doctors from the Centers for Disease Control and Prevention startled people last week with the finding that the prevalence of diagnosed cases of diabetes increased by a third (from 4.9 to 6.5 percent) between 1990 and 1998. But demographics explain only part of this "persistent explosion" of cases, says Dr. Frank Vinicor, director of the CDC's diabetes division; even among Caucasians--even those of normal weight--the rates are on the rise. The actual number is almost surely higher, since many cases go undiagnosed for years.

But the most alarming statistic in the CDC study was the breakdown of cases by age. For people in their 40s, the incidence of diabetes increased 40 percent over the eight years; for people in their 30s, it went up nearly 70 percent. "It's becoming a disease of the young," says Dr. Arthur Rubenstein, a leading endocrinologist and dean of the Mount Sinai School of Medicine in New York. In that light, Roman is an even more significant example. She is only 18, and she has type-2 diabetes, too.

In fact, until recently the disease Roman and her mother have was known as adult-onset diabetes, because it usually struck people middle-aged or older. The other kind was "juvenile" diabetes, now called type 1, which is an entirely different disease altogether. But in America, getting fat is no longer a prerogative of adults, and diabetes, which is strongly linked to obesity, is spreading down the age ladder. The rise in type-2 disease among teenagers is "extraordinarily worrying," says Rubenstein, because diabetes can take decades to reveal its most appalling effects--including ulcerating sores, blindness, kidney failure, strokes and heart disease. "If people become diabetic at age 10 or 15 or 20," he says, "you can predict that when they are 30 or 40, they could have terrible complications." You can also predict that they are going to need a lot of expensive health care; on average, medical-care spending for diabetics runs $10,000 to $12,000 annually--three to four times higher than on healthy people, every year for life. A number of promising new drugs and therapies may make diabetes easier to live with, but it will be a medical miracle if they end up saving money.

Diabetes is a disorder of the very engine of life, a subtle calamity at the molecular level. Its hallmark is a failure to metabolize glucose, the ubiquitous sugar molecule carried by the bloodstream to fuel every part of the body. Deprived of their prime energy supply, muscle and nerve cells slow their function, which is why early diabetes may manifest itself as lethargy and irritability. That was the experience of Maria DelMundo, 46, a Rochester, Minn., mother who weighed around 190 (she's 5 feet 2) when she stopped by her doctor's office for a checkup in 1991. "I just wasn't feeling good--tired and out of sorts," she recalls; in effect, she was undernourished even while eating her fill of the "buttery icing and whipped cream, French pastries and Hagen-Dazs" she loves.

At the same time, glucose accumulates in the patient's blood, and can reach concentrations two to three times normal and even higher. The excess is eventually excreted by the kidneys, which require copious quantities of water as a dilutant. That's how Keith Wein, 42, a mechanical engineer from Irvine, Calif., caught his diabetes--or, rather, his wife, Michelle, did. "I thought something was wrong when all of a sudden he started drinking water nonstop," says Michelle, a nutritionist. "He would come home from the grocery store with six or eight bottles of Crystal Geyser"--and spend a corresponding amount of time going back and forth to the bathroom. But these are subtle signs easy to overlook or deny. Steven Mallinson, a strapping six-foot, 190-pound hiker and cyclist, discovered he had diabetes at the age of 25 when he enrolled as a paid participant in a research study of a new drug, unrelated to insulin. The drug company took one look at his blood and urine samples and kicked him off the study, telling him to call his doctor immediately. "That's one of the problems," says Dr. Richard Hellman of the American Association of Clinical Endocrinologists. "A lot of people are walking around with either diabetes or a predecessor [condition] and they're not even aware of it. The symptoms are not specific, and they tend to come late."

Researchers are still investigating all the ways in which high blood-sugar levels do damage. One obvious effect is on the arteries, especially in the eyes, kidneys and extremities; sugar seems to both weaken the capillary walls and clog the small vessels. Hemorrhages destroy the retina; impaired circulation leads to ulcers in the legs and feet for which amputation may be the only cure. The risk of heart disease doubles for men; for women it goes up fourfold. Yet the misperception of diabetes as a relatively benign condition persists. "The word is not yet out about how serious it is," says Anne Daly of the American Diabetes Association. "There's no diabetes that's not bad. It's all serious."

Glucose metabolism is regulated by the hormone insulin, which is produced by the pancreas gland, a fist-size clump of tissue behind the stomach. In normal people, the pancreas secretes insulin in response to a rise in blood sugar, which happens after a meal. The relatively uncommon type-1 diabetes is marked by a straightforward shortage of insulin, which typically shows up around puberty. Researchers consider this an autoimmune disease, possibly brought on by a viral infection. And the treatment is straightforward in concept, if not always in practice: you supply the missing insulin, if necessary by injecting it before meals. Although the name "juvenile" diabetes has stuck, it's a disease you have for life; luckily, though, there's no evidence that its incidence is on the rise in the United States.

Type 2 is an altogether more complicated disease, a spiraling derangement in a network of positive and negative feedback loops linking the pancreas, liver (which stores and releases glucose), muscles, nerves, fat cells and brain (the only organ capable of deciding not to open a pint of rum-raisin ice cream). Perversely, the muscle cells refuse to absorb glucose from the blood, a phenomenon called insulin resistance. At least in the early stages of the disease, type-2 diabetics usually have normal insulin production. In fact, they may have above-normal insulin, as their pancreas produces more and more of it in a futile attempt to keep up with the rise in blood sugar. Over time, though, people may need more insulin than their pancreas can supply, and these patients, too, often become dependent on injecting themselves with insulin.

What could cause such a devastating misreading of biochemical messages? Inevitably, genetics seems to play a role. Just last week a team at the Whitehead Center for Genome Research identified a variant form of a gene on human chromosome 1 that appears to increase the risk of type-2 disease by about 25 percent--although it's carried by as much as 85 percent of the population, so having it doesn't seem to be cause for any special alarm. Certain population groups are especially prone to diabetes; among the Pima Indians of the Southwestern United States half of all adults suffer from it. Living in a harsh climate where food is naturally scarce during much of the year, they may have inherited a so-called thrifty gene that lowers metabolism in times of famine, at the price of increased susceptibility to diabetes. But it took the United States, land of the 40-ounce soda, to elevate that susceptibility to a crisis; the closely related tribe of Pimas in Mexico who farm and eat a traditional diet don't have nearly the same rate of diabetes. The correlation between type-2 diabetes and obesity is overwhelming: 13.5 percent of obese patients in the CDC survey had the disease, compared with 3.5 percent of those of normal weight. "As people get fatter, the risk of diabetes goes up dramatically," says Vinicor of the CDC. The exact nature of the relationship is extraordinarily complex and poorly understood, but the simplest way to think about it may be that for unknown reasons, the same things that make you fat also put you at risk for diabetes--lack of exercise and a high-calorie diet.

The very complexity of the glucose- insulin cycle, though, affords numerous opportunities to intervene with therapies. The obvious therapy, of course, is insulin. For years the only available form was harvested from cows or pigs, but now human insulin is being manufactured directly by recombinant DNA techniques. And not just insulin--drug companies are coming out with new and improved insulin, engineered with molecular changes to make it last longer in the body or be absorbed more easily into cells. Until recently, insulin had to be injected under the skin as often as five to seven times a day, in a complex calculus of food intake, energy output and dosage designed to keep blood sugar from going either too high or too low. Howard Mitchell of Bangor, Maine, 46, who weighs 280 pounds and is a type-2 diabetic, wears an insulin pump like a beeper, which he can program to deliver a measured dosage whenever he needs it. Now, he says, "my life is no different than anyone else's." An implantable version may be available soon; someday a completely self-contained unit may be able to measure blood glucose directly and deliver insulin automatically.

Other drugs, such as the sulfonylureas, which have been around since the 1950s, stimulate production and release of insulin by the pancreas; many type-2 diabetics take some form of these. But newer drugs, some introduced within the last year or two, offer far more possibilities for control. Glucophage is one; it controls blood sugar directly by promoting glucose storage in the liver. A class of drugs called TZDs make muscle and fat cells more sensitive to insulin, combating type-2 disease right at the source. And there are drugs that work in the gut to inhibit starch digestion, slowing the process enough to flatten the glucose "spike." "All these are new developments since 1995," says John Buse, director of the diabetes center at the University of North Carolina at Chapel Hill. "There's 255 different combinations of drugs, insulin, exercise and diet modification; I probably use 245 of them in my practice."

But there's another surefire way to control blood sugar and lessen the complications of diabetes; it calls for eating a healthy diet in the first place. A recurring theme in the conversations of diabetics is the foods they had to give up. Maria Mendoza, a college janitor in Los Angeles, cut down from "six or seven tortillas a day" to two after she was diagnosed with type-2 diabetes in 1985, and gave up "tacos, sweets, chocolates and pan dulce [sweet bread]." "I can't eat what I want, and that makes me sad," she says. "At times, I feel so deprived I want to cry." But increasingly, doctors have come to believe that an absolute ban on refined sugar is too restrictive. With conscientious monitoring of their blood sugar, regular exercise and the right attitude, many diabetics can now allow themselves an occasional sweet. Provided, of course, it is part of the same low-fat, high-fiber, low-calorie diet that researchers recommend for just about every other major problem in American public health. Sophisticated patients don't just stick to a diet: they monitor what they eat obsessively, and plot it against blood-sugar levels that they measure themselves (with a blood-glucose meter and a drop of blood from a finger) as often as five times a day. "My goal is to keep my glucose level under 150," says Michael Negrin, a 41-year-old New York businessman. (The number refers to milligrams of glucose per deciliter of blood.) "Yesterday I woke up and it was 179. I took my medicine and ate breakfast, and it went down to 122. After lunch, a corned-beef sandwich, I went up to 156. I worked out in the evening, and I was down to 58."

Evidence is also accumulating that the lack of exercise contributes to diabetes. Dr. Alan Shuldiner of the University of Maryland has been studying Amish families in Pennsylvania, who have about half the rate of diabetes found in the general Caucasian population--even though their diet is no healthier and the adults are just as likely to be fat. What sets them apart is that they don't have cars; when they're not riding a buggy, they're on scooters or roller skates, and (without telephones) they spend a lot of time going back and forth just to chat. And, says Shuldiner, with the absence of television, "you never see obese Amish children. Never."

It's a tough prescription, and the doctor hasn't been born yet who could get Americans to live like the Amish--even with those great pretzels and shoofly pie. But somewhere between the contemporary lifestyle and the 18th-century one there has to be a happy medium that can let us enjoy our food and comforts--and avoid the coming scourge of poisoning by sugar.

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