A questionable condition
Sweeping diagnosis In 2004 and 2010, the American Diabetes Association (ADA) expanded the blood sugar range it considers a sign of prediabetes, creating tens of millions of potential patients in the United States. The U.S. Centers for Disease Control and Prevention joined ADA in raising the alarm, portraying the condition as a first step toward frank diabetes.
Little risk Prediabetes does little or no harm on its own, and fewer than 2% of prediabetics in the ADA range progress to diabetes each year. Many studies suggest that for most people the usual treatments for prediabetes, diet and exercise, do little to further reduce the risk of diabetes.
Strong medicine Industry is developing at least 10 classes of drugs targeted to prediabetes. ADA also lists existing diabetes and weight loss drugs as options for people with prediabetes, and doctors are prescribing them “off label.” Many of those drugs can have serious side effects.
Money trails ADA and some of its physician advisers who have discussed drug treatments for prediabetes receive extensive financial support from pharmaceutical companies. The organization and its advisers say the payments have not affected their recommendations.
The most common chronic disease after obesity, afflicting 84 million Americans and more than 1 billion people worldwide, was born as a public relations catchphrase. In 2001, the PR chief of the American Diabetes Association (ADA) approached Richard Kahn, then the group''t easy, given the condition''s standards of care—widely regarded as the bible of diabetes. ADA and the Centers for Disease Control and Prevention (CDC) in Atlanta declared war against prediabetes, with CDC diabetes prevention chief Ann Albright, an ADA board member from 2005 to 2009, leading the charge. The two groups labeled prediabetes a first step on the road to diabetes, which can lead to amputations, blindness, and heart attacks.
In medicine, prevention is usually an unalloyed good. But in this case, other diabetes specialists argue, medical and epidemiological data give weak support, at most, for increasingly dire prediabetes admonitions. "" says Kahn, who left ADA in 2009 and is now at the University of North Carolina in Chapel Hill. The World Health Organization (WHO) in Geneva, Switzerland, and other medical authorities have rejected prediabetes as a diagnostic category because they are not convinced that it routinely leads to diabetes or that existing treatments do much good. John Yudkin, a diabetes researcher and emeritus professor of medicine at University College London, describes the ominous warnings about prediabetes from ADA and CDC as ""
Yet ADA, a nonprofit that funds research, issues treatment standards, and raises public awareness, has gradually broadened its definition of prediabetes to encompass more people. "" says William Cefalu, ADA''s lead, because "" Albright wrote in a statement to Science. (Albright declined interview requests, and CDC would not permit Edward Gregg, Albright''s own data show progression from prediabetes to diabetes at less than 2% per year, or less than 10% in 5 years. (Other studies show even slower rates.)
The push to diagnose and treat prediabetes has come at a cost. When told they have the condition, many people face psychological and financial burdens trying to address it. ADA, CDC, and other groups have spent billions of dollars on research, education, and health improvement programs—generally focused on weight loss and exercise—that have generated lackluster results, according to critics. Kahn makes the point with rhetorical bluntness: Spending vast sums of public money on such prevention programs ""
To lower blood sugar, ADA has increasingly advocated more aggressive measures, such as prescription drugs—a push that has opened it to charges of conflicts of interest. Science found that the group and its experts who promote aggressive treatment of prediabetes accept large amounts of funding from diabetes drugmakers. So far, no drugs have been approved specifically for prediabetes, meaning that doctors are limited to prescribing diabetes drugs or other medications "" to treat the condition. But drug companies are testing dozens of drugs aimed at prediabetes in hopes of tapping a potential worldwide market of hundreds of millions of people.
Given the avalanche of questionable spending and the wave of anxiety it has unleashed, Kahn now says he rues the day he helped promote the term prediabetes, calling it ""
ADA''s average blood sugar over the preceding 3 months. The expert committee urged that people with A1c readings of 6% or higher should be considered for preventive interventions. But it unanimously rejected the term prediabetes, saying it implies that prediabetic patients eventually will get diabetes and everyone else won''s new A1c standard, combined with its adoption of a similarly broad standard on a different blood sugar test a few years earlier, created about 72 million potential new prediabetes patients in the United States alone—and could create hundreds of millions more if embraced worldwide.
One of those Americans was Nance Yuan, a surgical resident in Los Angeles, California. In 2018, amid a demanding career, Yuan decided to freeze some of her eggs in case she wanted to have a baby later. A blood test before the procedure led to unwelcome news: prediabetes. Her result was borderline, so normally she would have been urged simply to improve her diet and to exercise more. But in light of her egg harvesting plans, Yuan''t take medicines as prescribed. "" she says. Even on good days, the diagnosis added a tinge of anxiety to her life.
In interviews and public statements over many years, Albright has suggested such anxiety is warranted. She has described prediabetes as a runaway train. Patients are "" she said at a 2016 medical conference. The media has reported, widely and with little skepticism, that prediabetes as defined by ADA and CDC is a serious health threat. Even Nutrition Action, a popular newsletter that debunks outlandish health claims, depicted diabetes as the tip of an iceberg with the prediabetes behemoth lurking below.
The broadened definition of prediabetes has triggered far-reaching changes in the medical landscape. CDC''s cancer prevention budget plummeted.) Many people diagnosed with prediabetes visit doctors more often for blood sugar tests and advice on diet and exercise. And a major marketing opportunity has opened up. Companies have pressured the Food and Drug the 1 last update 31 May 2020 Administration (FDA) for a seal of approval on foods or supplements—such as coffee, dairy products, and sugar substitutes—that they say can help prevent diabetes. A cottage industry of specialty fitness coaches emerged to serve a multitude of worried prediabetes patients.The broadened definition of prediabetes has triggered far-reaching changes in the medical landscape. CDC''s cancer prevention budget plummeted.) Many people diagnosed with prediabetes visit doctors more often for blood sugar tests and advice on diet and exercise. And a major marketing opportunity has opened up. Companies have pressured the Food and Drug Administration (FDA) for a seal of approval on foods or supplements—such as coffee, dairy products, and sugar substitutes—that they say can help prevent diabetes. A cottage industry of specialty fitness coaches emerged to serve a multitude of worried prediabetes patients.
Several companies target prediabetes patients for sales of continuous glucose monitors that attach to the body and transmit data to smartphones. Market analysts say makers of the devices—which can cost thousands of dollars annually—could add 25 million customers in the next 12 years in the United States alone, with prospects of a much larger global market, including China. Simpler home glucose testers, such as those used in finger sticks, are a razors-and-blades proposition. A starter model costs just $11.55 on Amazon, but requires branded test strips. Writing recently in Psychology Today, a physician and nutrition consultant touted home glucose testing after every meal as the top medical necessity for everybody—regardless of health or blood sugar status.
As the market expands, individual patients and society as a whole face a steep price tag. In 2014, failing to note its own role in widening the patient pool, ADA warned of "" U.S. prediabetes spending, estimated at $44 billion in 2012 (the most recent year for which data are available)—about 1.6% of all health care costs and 74% higher than in 2007. Even if that is an exaggeration, as some say, costs are substantial and rising.
Cefalu says lower-cost interventions are needed, but he describes many current programs as cost-effective, and a medical and moral necessity. In a recent article about diabetes prevention, he invoked Winston Churchill''s average glucose levels are at the low end of the test result spectrum for 1 last update 31 May 2020 as defined by ADA?Cefalu says lower-cost interventions are needed, but he describes many current programs as cost-effective, and a medical and moral necessity. In a recent article about diabetes prevention, he invoked Winston Churchill''s average glucose levels are at the low end of the test result spectrum as defined by ADA?
On one side are CDC and ADA, powerful financial gatekeepers and opinion leaders. ADA journals are the field''s research and programs on diabetes prevention. On the other side are public health and primary care authorities, including WHO, the U.K. National Institute for Health and Care Excellence, EASD, and IDF. Those groups either do not use or do not emphasize the term prediabetes, and they normally advise treatment only when blood sugar levels approach those of frank diabetes.
Researchers skeptical of the ADA definition point to a comprehensive 2018 review of 103 studies by the Cochrane Library in London, which showed that most people who qualify as prediabetic never progress to diabetes over any period studied. People who do progress usually start out at the higher end of the ADA prediabetes test range. The review also noted that studies of people labeled prediabetic often fail to account for weight, age, and physical activity, which can all affect glucose, as can daily stress, inflammation, and other factors. According to the review, up to 59% of prediabetes patients returned to normal glycemic values over 1 to 11 years with no treatment whatsoever.
"" the Cochrane authors concluded, ""
reverses diabetes type 2 and coronavirus (☑ by race) | reverses diabetes type 2 zucchinihow to reverses diabetes type 2 for Kahn adds that even people whose elevated blood sugar does lead to diabetes progress slowly. "" he says. Prediabetes itself does not raise the risk of cardiovascular disease or other complications of diabetes, says former ADA President Mayer Davidson, a physician now at Charles R. Drew University of Medicine and Science in Los Angeles.
To support the value of aggressive treatment, ADA and CDC cite a landmark clinical trial of prediabetes, the Diabetes Prevention Program Outcomes Study (DPPOS), which began in 2002 and is still collecting data. Sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases and conducted by researchers at 25 centers across the nation, it included nearly 3000 prediabetic subjects randomly separated into three groups. One received intensive diet and exercise interventions, one took metformin, and a control group got neither. Fewer people in the treatment groups progressed to diabetes over 6 years—5.3% per year in the lifestyle group and 6.4% for the metformin group, compared with 7.8% in the control group, DPPOS scientists reported in 2009 in The Lancet.
The study''s more common A1c. On average, the people studied were less healthy than most people within ADA''t provide. Henry Kahn (no relation to Richard Kahn), a former CDC physician who retired from Albright''s diabetes program, says ADA''s prediabetes definition. The federal registry ClinicalTrials.gov lists human tests for more for 1 last update 31 May 2020 than 100 drugs, supplements, and other prediabetes remedies, including devices such as gastric bands. Drugmakers, ADA, and others have funded trials for at least 10 classes of drugs.The study''s more common A1c. On average, the people studied were less healthy than most people within ADA''t provide. Henry Kahn (no relation to Richard Kahn), a former CDC physician who retired from Albright''s diabetes program, says ADA''s prediabetes definition. The federal registry ClinicalTrials.gov lists human tests for more than 100 drugs, supplements, and other prediabetes remedies, including devices such as gastric bands. Drugmakers, ADA, and others have funded trials for at least 10 classes of drugs.
So far, FDA has approved no drug or device for prediabetes. Approval timelines remain hazy because the agency has yet to define clear therapeutic goals, says Todd Hobbs, U.S. medical officer for Novo Nordisk, a leading diabetes drugmaker based in Bagsværd, Denmark. "" he asks. Hobbs says FDA eventually will pick some criteria. Prediabetes "" he says. ""
Meanwhile, doctors can treat prediabetes with a rising number of drugs prescribed off label—most approved for diabetes or obesity. In 2007, ADA began to recommend metformin as a relatively safe, inexpensive, long-term option for prediabetes patients with other risk factors for diabetes, such as obesity. Then, in 2013, ADA joined other advocates of aggressive diabetes prevention in listing more powerful, costlier drug options.
Cefalu says ADA still discourages using any drug except metformin for prediabetes. But since 2013, ADA standards of care have consistently listed a variety of diabetes and obesity drugs that it says may decrease the incidence of diabetes among prediabetics. ADA urges doctors to consider "" but does not advise against prescribing the drugs, as it did in the past.
It seems counterintuitive to take a medicine in order to prevent something for which you would take that medicine.
Some physicians are trying new drug options on ADA''s A1c scale—barely prediabetic. They were given a cocktail of either two or three diabetes drugs. On average, their blood sugar decreased slightly.
Any drug for prediabetes would likely have to be taken for years, perhaps a lifetime, so such modest benefits must be weighed against the potential harms of continual treatment. And several prediabetes options described by ADA and others present serious hazards. Pioglitazone, a drug to lower blood sugar developed by the Tokyo-based Takeda Pharmaceutical Company under the brand name Actos, carries on its label a "" side effect warning of the risk of congestive heart failure. The drug can also raise the risk of bone fractures and cancer. Exenatide (branded Bydureon by Cambridge, U.K.–based AstraZeneca), which reduces blood glucose and suppresses appetite, has a black box warning for thyroid cancer. Liraglutide (sold as Victoza by Novo Nordisk) also carries warnings of potentially lethal side effects.
Yudkin says the growing emphasis on drugs for prediabetes reflects in part a false sense of urgency about its health risks. WHO''s conflicts as among the most extreme. An ADA representative wrote in an email to Science that its funders have no influence over "" of ADA''s expanded prediabetes definition is a financial win for physicians, companies that conduct lab tests, drug companies, device and app developers, clinics, and hospitals, says Victor Montori, a diabetes clinician at the Mayo Clinic in Rochester, Minnesota. "" often at considerable expense.
I just don’t think we [prevent diabetes] by making every healthy person a patient.
Yuan, the surgical resident, had her eggs frozen after a few months of prediabetes treatment. With great relief, she stopped taking metformin—which several diabetes and fertility experts say was overtreatment in her situation. But the prediabetes diagnosis and prescription remain on her medical record, which could affect her future insurance premiums. Other people given a prediabetes diagnosis face greater challenges: For example, according to a recent study, Medicare reimburses just a small fraction of costs for its own diabetes prevention program.
The insurance problem is one sign of what happens when a borderline medical test result becomes "" turning many basically healthy people into stressed-out patients, critics of ADA's prediabetes definition say. "" asks Davidson, the former ADA president.
Many public health organizations believe a mainly clinical approach to diabetes prevention is ineffective. WHO, for example, favors societywide solutions, which aim to address the health impacts of social stratification and failures of urban planning. It endorses laws that help reduce consumption of sugary drinks and unhealthy foods.
A 2011 study in JAMA examined health outcomes in women living in stressful, low-income housing projects who had been randomized into three groups: One got a voucher for better housing and help moving, one a voucher for moving to any area without help, and a control group got neither. Women who got the most housing assistance suffered the least obesity and diabetes—over 20 years, about 15% had become diabetic, compared with 20% in the control group.
"" Montori says. Diabetes can and should be prevented, he says. ""
Jia You and Meagan Weiland contributed reporting. This story was supported by the Science Fund for Investigative Reporting. If you want to contribute to similarly ambitious investigations, please give a tax-deductible gift to the fund today.