Although a 3 percent gain per year might not sound like much, the magic of compounding means that this pace of growth would lead to a doubling in the rate of new cases of type 1 diabetes in 23 years. Clusters of cases, like the one reported in Weston, may become increasingly common.

Sure enough, soon after her letter appeared in The Boston Globe, Ann Marie Kreft heard from parents in nearby towns with similar concerns. In Concord, the site of Walden Pond, five children were diagnosed with type 1 diabetes during the 2007–08 school year. In Mansfield, another suburb of Boston, a total of 18 kids in the school system had the disease, enough to spark a parents’ meeting in October 2008. In Sudbury the number of diagnosed children in the school system stood at an astonishing 27. And outside of Massachusetts, Kreft searched the Web and found families in the suburbs of Denver, Phoenix, and Detroit who had the same concerns about apparent clusters of type 1 in their neighborhoods.

The same questions echoed from the parents in each of those communities: Why is this happening to our kids? Why would the incidence of a once-rare autoimmune disease be rising? What on earth has changed in the past 50 years?

Terry Wilkin had his foot on the accelerator of his bright orange 1976 Volkswagen camper van, his wife beside him and their three kids in the backseat, as they drove through the Austrian Alps on a rainy day in August 1986. That is when he was struck by his Big Idea, one that he honed in discussion with his wife along the road. As they talked, it became apparent to him that the orthodox view on what causes type 1 diabetes (and, by extension, on why it could be increasing) had sustained a major dent.

Wilkin’s idea was as simple as it was heretical. As a professor of endocrinology and metabolism at Peninsula Medical School in Plymouth, England, and the founder of the respected scientific journal Autoimmunity, Wilkin knew he was going against the well-established understanding of type 1 diabetes that had been worked out half a century earlier. Back then, biologists were struggling to learn how the fierce little warriors of the immune system—the white blood cells—know to attack invading pathogens but not the body itself.

Understanding that process would in turn help explain what goes wrong in an autoimmune disease like type 1 diabetes, when those immune cells go rogue and turn the attack inward. Here was a question of biology that even a poet or philosopher could love: How does the body distinguish between self and nonself, I and Thou?

The standard explanation, developed in the 1930s, is that every cell in the body is tagged with a self-identifier, the molecular equivalent of a Do Not Disturb sign on a hotel doorknob. This sign is called the major histocompatibility complex, or MHC. For every individual, the MHC affixed to cells serves as a signal of that person’s unique identity. That is why the roaming T and B cells of the immune system can go after invading microbes (nonself) while leaving its own cells and organs (self) intact. When the immune system nonetheless attacks self-cells, that error has typically been attributed to a signaling problem, either a misspelled sign placed on the cell’s doorknob or a misreading by T and B cells on the hunt. Indeed, most of the genetic risks linked to type 1 diabetes have been mapped to variants in the MHC. Nothing is wrong with the organ under attack, the experts have held. Rather, the fault lies with the immune system itself. To cure the autoimmune disease, then, all you would have to do is to fix the faulty signals that have led to the errant attack on the body’s own organs.

That is exactly what diabetes researchers have been trying to do since the 1970s, when type 1 was proved to be an autoimmune disorder. So far, though, they have struggled to turn off the immune attack without using immune-suppressing drugs so potent that they can cause side effects as severe as diabetes itself.

The school nurses had never seen anything like it. There were now eightchildren with type 1 diabetes attending Weston public schools.

Wilkin’s idea sounded ridiculous to the immunologists who first read about it in the pages of Autoimmunity, and it still sounds foolish to many diabetes specialists. Autoimmune disorders, Wilkin proposed, might not be disorders of the immune system after all. Maybe the immune system is actually working just fine. Maybe the organs that come under attack actually have something wrong with them and are sending the standard, appropriate signals to the immune system that all damaged cells use to have the molecular garbage collectors sweep them away. Maybe, he proposed, the immune attack is really just the smoke, not the fire.

Although he initially proposed this idea as a new theory of auto­immunity in general, Wilkin soon homed in on type 1 diabetes in particular. To bolster his case, he took, magpielike, from a startling array of seemingly disconnected study findings and emerging trends.

First was the indisputable fact that both type 1 and type 2 diabetes were rising, seemingly in sync.

Second, people with type 1 were showing many of the same characteristics as those with type 2, and vice versa. For instance, children and adults with type 1, though not generally obese, were often found to weigh more, on average, than their friends and family members without the disease. In fact, those children who eventually develop type 1 are heavier, on average, as toddlers than are their peers who never do. At the same time, 30 percent of those with type 2 diabetes had the same auto­antibodies to their beta cells—the insulin-producing cells in the pancreas—associated with type 1. This makes no sense if obesity is the only cause of type 2.

Third, insulin resistance, the diag­nostic hallmark of type 2, could sometimes be detected in children before they developed type 1.

Fourth, just as type 2 was being seen in younger and younger people, in their twenties and teens, so type 1 was also being seen at younger and younger ages. There was an ever-increasing proportion of children stricken under age 5.

Fifth, the proportion of type 1 dia­betics who have the susceptibility genes associated with a high risk of developing the disease is getting smaller and smaller, suggesting that genetics is playing a lesser role.

Wilkin took these and other facts, shook vigorously, and brought forth what he called the accelerator hypoth­esis, named not in honor of his rapid drive through the Alps but for the way in which increased growth accelerates the risk of type 1. First set in print in July 2001 in the eminent European journal Diabetologia, Wilkin proposed that type 1 and type 2 are really two faces of the same disease, both rooted in weight gain and distinguishable only in degree. A person with a strong genetic tendency to develop diabetes will do so at the drop of a hat, with even a modest increase in childhood weight, and develop what we call type 1. Someone with less of a genetic predisposition will develop it more slowly, requiring more time, more weight, and more insulin resistance, and will be labeled as having type 2. The increase in weight, in other words, has accelerated the development of diabetes both in those with the greatest inborn genetic risk and in those with the least.

To many physicians who treat diabetes, and to many diabetics as well, this new interpretation initially seemed so ridiculous as to be unworthy of serious consideration. A major stumbling block for some doctors was their mistaken notion that Wilkin sought to negate the decades of research establishing an autoimmune attack as the primary cause of type 1. Actually, Wilkin was seeking out the factors that help induce and speed up an autoimmune attack.

The accelerator hypothesis has now been the subject of dozens of scientific papers. Despite receiving angry public dressings-down at major medical conferences by some of the most prominent researchers in the field, Wilkin insists that no serious refutation of it has yet been offered, whether conceptually or experimentally, and that no other compelling hypothesis has been presented to explain the puzzling set of facts.

At present, at least half a dozen studies from around the world have borne out the relationship between weight and type 1. In Britain, a 2003 study led by Wilkin involving 94 children with type 1 found that the greater their body mass index (BMI), the younger their age of diagnosis. In Germany and Austria, a 2005 study of 9,248 children with type 1 concluded, “A higher BMI was associated with a younger age at diabetes onset.” In Australia, a study published in January 2009 followed 548 children from birth, all of whom had a parent or sibling with type 1 diabetes. By age 8½, 46 of the children had autoantibodies to their own insulin-producing beta cells; as weight and BMI went up, so did their risk. And according to a 2008 study out of Sweden, the relationship holds not only for weight and BMI but also for height. Altogether, it appears that the faster a child grows, whether up or out, the greater the stress on the insulin-producing beta cells in the pancreas and the higher the odds of setting off an autoimmune attack that results in type 1 diabetes.

As evidence grows in support of Wilkin’s accelerator hypothesis, he reiterates that he is not claiming type 1 and type 2 diabetes are identical, or that weight gain alone “causes” type 1. Rather, he holds that weight accelerates the action of two other variables: some children’s genetic tendency to develop insulin resistance in response to increased weight and some children’s genetic tendency to have a highly reactive immune system. A hundred years ago, when people were, on average, shorter and thinner, only kids with hair-trigger immune systems developed type 1, and only heavy older adults with a strong tendency toward insulin resistance developed type 2. Weight, according to the accelerator hypothesis, is the enhancer—the MSG, the Special Sauce—of diabetes risk.

Still, the hypothesis has raised a firestorm of controversy that has yet to die down. “I think it’s nonsense,” a respected type 1 researcher told me after insisting that I not publish his name because he knows and respects Wilkin personally. “My opinion is that a common pathway for type 1 and type 2 is definitely not correct. I do not think obesity is a primary trigger of the autoimmune process.” Other researchers take a more nuanced view. “The last 15, 20 years, there has been an enormous increase of weight in Swedish children,” says Swedish pediatrician Johnny Ludvigsson of Linköping University, who greets the theory with interest. “If you take a group of 10-year-old children, they weigh on average half a kilo [about one pound] heavier than 10-year-olds did the year before. Every generation is heavier than the last.”

Ludvigsson emphasizes that weight is probably not the only thing that can press the immune system’s attack on the insulin-producing beta cells. “A lot of different factors stress the beta cells or lead to increased demand for insulin. Even psychological stress can lead to counter-regulatory hormones, which lead to more insulin and more stress on the beta cells,” he says.

Likewise, British endocrinologist Edwin Gale, the editor of Diabetologia, agrees that other accelerators, whether genetic, metabolic, or immune, are also likely to be present. But what might they be?

Already, exposure to standard infant formula in the first six months of life has been strongly associated with an increased risk of type 1. So persuasive is the connection that 2,160 children at 77 medical centers in Europe, Australia, and North America are now being tracked to see whether hypoallergenic formulas or good old breast milk will lower the risk. Other studies have tied an increased risk of type 1 to pollutants, low levels of vitamin D, and the increasing age of pregnant mothers. Some researchers have even tied higher rates of type 1 with increased wealth and with more stringent levels of hygiene.

So far these are just correlations, however. The connection between these factors and type 1 diabetes is unproven. Whether they are also responsible for the increasing rate of other autoimmune disorders is equally provocative and equally unknown (see “Chronic Kids,” below).

“You wouldn’t want to take something based on speculation without proof,” says Judith Fradkin, director of the Division of Diabetes, Endocrinology, and Metabolic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “All sorts of things are correlated with an increased or decreased risk of type 1. But it’s very hard to separate out from an epidemiologic study what is actually causative.” Whatever the cause, Fradkin says, this much is clear: “The type 1 rates are rising. Something has to be behind it. We need to find it. If we find it, that has tremendous implications for prevention.”

To get answers, NIDDK is cosponsoring the Environmental Determinants of Diabetes in the Young (TEDDY) study, which is in the process of screening a third of a million newborns in the United States and Europe. The ultimate goal is to follow 7,800 children at high risk of developing type 1 through age 15. “Using the genomic analysis of stool samples,” Fradkin says, “we may find an unsuspected bacterium or virus that promotes or protects against type 1. We’re also collecting nasal swabs and sampling tap water. We’re collecting a lot of samples, and then we’ll see who develops diabetes and who doesn’t. Whatever the trigger, we want to find it, because we do think it’s environmental.”

Which brings us back to Weston. Since the initial outbreak of type 1 during the school year of 2007–08, the numbers have only gone up. Ann Marie Kreft, whose son Gus was one of the first children diagnosed in the cluster, remains frustrated at the lack of a comprehensive registry to record type 1 diabetes cases across Massachusetts or, for that matter, around the country. (Massachusetts has begun to collect records, but only for grades K–8.)

Although the CDC and NIDDK are now tracking incidence rates in six U.S. communities and running the TEDDY study, at present only one state requires all cases of type 1 diabetes to be reported to the public-health department: Oregon. A law mandating the practice was passed back in 2001. And even in Oregon, the state’s health department put in place the computers, forms, and systems to handle the diabetes reports only last year and has yet to publish any figures or analysis. Astonishingly, there is no national tabulation of type 1 diabetes cases at all.

And so, to this day nobody really knows how aberrant the Weston-Wellesley cluster is. An epidemic seems to be under way, yet we understand very little of what is happening. Only when the reporting of type 1 becomes mandatory nationwide will scientists be able to track the big picture and the local variations that could prove crucial in putting Wilkin’s ideas to the test. Only then will they unravel the riddle of why type 1 continues to rise and how we might prevent it.

From Diabetes Rising by Dan Hurley. Copyright ©2010 by Dan Hurley. Reprinted by permission of Kaplan Publishing, a division of Kaplan, Inc.

Chronic Kids

On its face, the report is shocking: According to a study in the February Journal of the American Medical Association, chronic childhood health conditions—from allergies to learning disabilities—have doubled in recent decades. Many researchers think the increasing prevalence of childhood obesity plays a role in this trend.

There are other causes too. Massachusetts General Hospital pediatrician Jeanne Van Cleave, a study author, points to increased survival of babies born with health complications and improved screening and diagnosis—the latter an argument used by some to explain the surge in diabetes and autism. Poverty may be a factor. From 2003 to 2007 obesity increased by 10 percent in United States children but 23 to 33 percent among low-income kids, according to an Annals of Epidemiology report. “The brain and immune system may develop differently in children in very stressful environments,” says Neal Halfon, a professor of pediatrics at UCLA. Environmental toxins are also key. “Air pollution is part of the story with regard to respiratory disease. Childhood cancer, learning disabilities, and autism can possibly be tied to early exposure to toxins,” says pediatrician Philip Landrigan, director of Mount Sinai’s Children’s Environmental Health Center in New York.

The bleak report has one uplifting note: The conditions appear largely preventable. “Many children grew out of conditions as they got older,” Van Cleave says. Answers may emerge from a new NIH study correlating social and physical environment with health in about 100,000 kids.  —Amy Barth