An article by the investigative journalist Charles Piller in the March 2019 issue of Science questions whether the current definition of prediabetes is too broad to be meaningful at all. The report revives prior conversations about how conflicted interests and profit motives may factor into the diagnosis. Here’s what you need to know about the current debate, and in the wake of it, how to approach a prediabetes diagnosis from your doctor.
The condition of prediabetes by itself does little or no harm, and relatively few people who have the condition, according to the American Diabetes Association (ADA) guidelines, develop diabetes annually. Data from the Centers for Disease Control and Prevention (CDC), Piller writes, “show progression from prediabetes to diabetes at less than 2 percent per year, or less than 10 percent in five years.” He says this figure is based on the CDC’s estimate that 84 million people in the U.S have prediabetes, and that 1.7 million people 20 and over are newly diagnosed with the disease every year.The pharmaceutical industry is developing at least 10 classes of drugs targeted at people with prediabetes. In addition, doctors are prescribing existing diabetes and weight loss drugs that can have serious side effects off label to people with prediabetes, and the ADA is also listing these drugs as options.The ADA and some of its physician advisers who have discussed medications for prediabetes receive “extensive financial support” from drugmakers.
On April 13, 2019, Piller told Everyday Health that the response he had received from doctors, patients, and researchers to the article, and a similar analysis in the Los Angeles Times, had been “overwhelmingly positive, though naturally there have been a few critics as well.” He has not heard directly from anyone in the pharmaceutical industry. Subsequently, the ADA published an article in the April 26, 2019 edition of Science disagreeing with several assertions in Piller’s article. “C. Piller asserts that prediabetes diagnoses and treatment may be ineffective and sullied by conflicts of interest. As current and former chairs of the ADA’s Professional Practice Committee [the group that reviews and updates the Standards of Medical Care in Diabetes each year], we disagree,” the letter’s authors say. “Prediabetes is a useful term to convey future risk of diabetes, and recommendations for diabetes prevention are based on best current evidence.” RELATED: 5 Bad Habits That May Increase Your Risk of Prediabetes Since 1980, the World Health Organization has identified two states that indicate a high risk for developing diabetes: impaired glucose tolerance and impaired fasting glucose, according to a January 2014 article published in the Lancet. Impaired glucose tolerance means blood sugar levels are consistently above normal yet below the level of diabetes. Meanwhile, impaired fasting glucose means blood sugar levels are consistently above normal while fasting, but below the level of diabetes, which may exist in the absence of impaired glucose tolerance. The specific definitions are: Impaired glucose tolerance (IGT) A reading of 140 milligrams per deciliter (mg/dl) to 199 mg/dl (7.8 millimoles per liter [mmol/l] to 11.0 mmol/l) two hours after taking an oral glucose tolerance test, which involves drinking a sugar solution Impaired fasting glucose (IFG) A fasting plasma glucose (FPG) reading of 110 mg/dl to 125 mg/dl (6.1 mmol/l to 6.9 mmol/l) In 2003, the ADA issued guidelines that lowered the impaired fasting glucose threshold to an FPG of 100 mg/dl (5.6 mmol/l). Piller’s article in Science notes that around this time the organization coined the term “prediabetes” to better motivate doctors and patients to take diabetes risk seriously. “Within a relatively short period of time we … eliminated ‘impaired fasting glucose’ and ‘impaired glucose tolerance’ and substituted ‘prediabetes’ in all of our literature," said Richard Kahn, PhD, the former chief scientific and medical officer of the ADA, according to the article. Piller continues: “Soon, the term was enshrined in the Arlington, Virginia, group’s standards of care — widely regarded as the bible of diabetes. ADA and the 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.” According to an article in Diabetes Care, in 2009 an international expert committee composed of the ADA, the European Association for the Study of Diabetes, and the International Diabetes Federation (IDF), announced that people with readings between 6.0 and 6.4 in the hemoglobin A1C test “should receive demonstrably effective preventive interventions.” A1C measures how much glucose, on average, attaches to the hemoglobin in your red blood cells over the previous three months. But they did not embrace the term prediabetes, which they described as “problematic because it suggests that all individuals so classified will develop diabetes and that individuals who do not meet these glycemia-driven criteria (regardless of other risk factor values) are unlikely to develop diabetes — neither of which is the case.” A year later, the ADA added the A1C test to its guidelines for diagnosing prediabetes and lowered the diagnostic threshold to 5.7, a move that the IDF and WHO did not endorse. Nevertheless, the CDC followed suit. When asked to comment for this article, Ann Albright, PhD, RD, the director of the CDC’s Division of Diabetes Translation, said in a statement that the agency adopted the ADA’s prediabetes testing recommendations “because the ADA sets the primary standards of care for diabetes in the U.S.” After that, “The numbers had expanded from 11 percent of the U.S. adult population to about 35 percent of the U.S. adult population now,” says John S. Yudkin, MD, a diabetes researcher and emeritus professor of medicine at University College London in the United Kingdom. For the Science article, Piller interviewed Dr. Yudkin, who has been a longtime critic of the prediabetes diagnosis, calling the CDC and ADA’s caution about prediabetes “scaremongering” in the article. The further you get away from the original threshold, the lower the risk, Yudkin says. RELATED: Type 2 Diabetes Complications You Can Avoid Yet Gregory A. Nichols, PhD, one of the coauthors of the Permanente Journal study, cautions against overlooking those who are closer to the 5.7 A1C cut point, because they can progress upward along the spectrum over time toward diabetes. “Once you get to 5.7, it’s probably going to progress to 6.0 within the next two years, then to 6.5 a few years after that. It’s safe to say that even at the low end, your risk of diabetes is increased. It might just take you longer to get there.” Put into perspective, the lifetime risk of an American adult developing diabetes is 40 percent, according to a separate, November 2014 study published in The Lancet: Diabetes and Endocrinology, which cites Nichols’s study. Another argument for keeping the threshold at 5.7 is that the A1C test isn’t necessarily the most reliable test for diagnosing impaired glucose tolerance and diabetes anyway. Maria Mercedes Chang Villacreses, MD, a professor of clinical diabetes, endocrinology, and metabolism at City of Hope National Medical Center in Duarte, California, coauthored a study of the effectiveness of the A1C test versus the oral glucose tolerance test (OGTT), which is used less often because it’s more expensive and time-consuming. The study found that the A1C test didn’t catch 73 percent of diabetes cases that were detected by the OGTT, and was particularly inaccurate in black and Hispanic people. The researchers presented these findings at ENDO 2019, the annual meeting of the Endocrine Society, in March 2019, but they have not yet published them in a peer-reviewed journal. “Since we are seeing that the A1C test is missing a lot of people, maybe we should try to study if a lower A1C number would be better at catching these people earlier. But that still needs to be studied,” says Dr. Chang Villacreses. RELATED: A1C Test May Fall Short in Diagnosing Diabetes in Some People, Early Study Finds Rahil Bandukwala, DO, an endocrinologist at MemorialCare Saddleback Medical Center in Laguna Hills, California, says the prediabetes diagnosis starts a conversation with patients about their health and lifestyle changes they can make, such as losing weight, to head off potential problems down the road. “It’s not going to hurt you to do those things. At least you are taking some action and you will be proactive and you are aware, more aware than you were before you knew that number.” But he adds that in his practice he sees “a very small number” that actually progress from prediabetes to diabetes, and does not believe it’s defined in an optimal way. “I think there are other [contributing] factors with those patients that do progress — other health factors, whether it is genetics, family history, medical conditions, and medications that they are taking.” The ADA’s letter in Science reflects the importance of other contributing factors. “The risk of progressing from prediabetes to diabetes varies according to the diagnostic criteria used.” Referring to Piller’s assertion that CDC data shows the progression from prediabetes to diabetes at less than 2 percent per year, the ADA adds, “Even a 2 percent progression rate per year would translate to nearly 1 of 5 people with prediabetes developing diabetes within 10 years. Also, many individuals with prediabetes have a multiplicity of risk, due to ethnicity, body weight, and other factors, and these may render their annual risk much higher.” The ADA and CDC’s prediabetes treatment recommendations emphasize lifestyle changes, says Albright, of the CDC. “Research has shown that lifestyle changes, such as improved diet, increased physical activity and stress reduction/coping have proven effective at preventing or delaying type 2 diabetes in people at risk, and remain a necessary part of prevention efforts,” she says. RELATED: How Your Genes Can Play a Role in Whether You Develop Diabetes Albright also points to a landmark CDC-led randomized controlled clinical study known as the Diabetes Prevention Program Outcomes Study (DPPOS), which looked at methods to delay or prevent diabetes in those who already had prediabetes. It found that after three years, an exercise and diet regimen aimed at 7 percent weight loss reduced subjects’ risk of developing diabetes by 58 percent, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). In a 10-year follow-up study, the program had reduced the rate of progression to diabetes by 34 percent, and delayed the onset of diabetes in those who did progress from prediabetes to diabetes by about four years. The study also looked at the use of the popular diabetes drug metformin in people with prediabetes, and found that the drug reduced participants’ progression from prediabetes to diabetes by 18 percent, and delayed their onset of diabetes by two years. The ADA recommends metformin for people with prediabetes for preventing diabetes, particularly if the person is obese, over age 60, or has a history of gestational diabetes. “I do use metformin if I think it’s appropriate,” says Dr. Bandukwala. “I don’t shy away from it. Sometimes I will even talk about some of the newer agents, especially if they are struggling with weight. I will bring up the [Glucagonlike peptide-1] agonists as potential drugs that could be a good mechanism for them not only to lose weight but prevent diabetes.” GLP-1 receptor agonists include Victoza or Saxenda (liraglutide), and a study published December 2013 in the American Journal of Health-System Pharmacy suggests these drugs may help people without diabetes lose weight if they’re not seeing success through diet and lifestyle changes. RELATED: Does Metformin Cause Weight Loss? What to Know Before You Take It Furthermore, focusing on creating a very broad category of people based primarily on their blood sugar readings may miss the point of why many healthcare providers are concerned about diabetes in the first place. “With diabetes the problem is not the blood sugar itself but all the bad things that it does to you as a result — the increased risk of cardiovascular disease, of blindness, of kidney failure,” Nichols says. Yudkin calls the focus on prediabetes “glucocentric,” and suggests that a motivation behind it includes a drive for market share by medical specialists such as endocrinologists and pharmaceutical companies. “It’s an interesting phenomenon, this medicalization of society and the drug industry moving from treatment of common diseases to the treatment of ‘pre’ diseases because the market is huge. The epidemic of obesity and diabetes in emerging economies is really where the pharmaceutical industry is aiming.” RELATED: Researchers Identify 5 Types of Diabetes in New Study As a 2011 article in Diabetes Care noted, the International Diabetes Federation estimates that 472 million people worldwide will have impaired glucose tolerance, one of the indicators of prediabetes, by 2030. That’s a potentially huge market for those who create products for the monitoring and control of blood sugar, as Yudkin says. In the ADA’s latest standards of care, which it published in January 2019 in Diabetes Care, the organization not only recommends metformin, but it also lists other types of drugs that doctors may prescribe for prediabetes treatment. Those drugs include a-glucosidase inhibitors, such as Precose (acarbose) and Glyset (miglitol); glucagonlike peptide 1 receptor (GLP-1) agonists, which include liraglutide (Victoza, Saxenda); and thiazolidinediones, which include Actos (pioglitazone) and Avandia (rosglitazone); though the ADA cautions, “One has to balance the risk/benefit of each medication.” Piller argues that in some cases, those drug risks may outweigh the benefits. “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,” he writes in Science. “And several prediabetes options described by ADA and others present serious hazards.” Among them are Actos, which has a black box warning that it may cause or worsen congestive heart failure, per GoodRx; and Avandia, which carries an elevated risk of heart attack, according to the FDA. In its letter in Science, the ADA puts its descriptions of medications in the standards of care in this context: “The only recommended medication is metformin, which has been shown to be effective and safe and is available for as little as $4 per month, rendering the conflicts of interest described in the article irrelevant to the current ADA recommendations for diabetes prevention.” The authors of the October 2018 Cochrane Library article, which looked at reversion to normal glucose levels, also expressed concern. “Doctors should be careful about treating prediabetes, because we are not sure whether this will result in more benefit than harm, especially when done on a global scale affecting many people worldwide,” they wrote in their paper. Bernd Richter, MD, PhD, who is on the medical faculty of the Heinrich-Heine University in ;Düsseldorf, says that medications typically used to treat diabetes, which are often the same ones used with prediabetes, can come with unwanted side effects. Those medications include metformin, sulfonylureas (like glibenclamide), glinides (like nateglinide), thiazolidinediones (like pioglitazone), DPP 4 inhibitors (like sitagliptin) and SGLT2 inhibitors (like empagliflozin), Richter says. MedlinePlus notes that common side effects of taking metformin include diarrhea, bloating, and other gastrointestinal symptoms. A study published November 2017 in Diabetes, Obesity, and Metabolism suggests these side effects may help explain why patients don’t take nearly one-third of their prescribed doses. Meanwhile, Piller writes in his article that financial conflicts of interest abound, particularly for prominent diabetes researchers and within the ADA. “In recent years, ADA says, it has received $18 million to $27 million annually from drug companies, including many donations of $500,000 to $1 million per year. The group also gets up to $500,000 annually from each of more than a dozen other firms in the diabetes and prediabetes markets, including makers of consumer and medical products, testing labs, insurance companies, and drug retailers.” A look at the ADA’s corporate supporters page shows donations from the types of companies that he is describing. The ADA denies that funders have any influence over its work. Furthermore, despite the market potential, even the top-recommended medication to manage prediabetes — the relatively inexpensive metformin — is prescribed to and used by only a small percentage of people in the U.S. Metformin has an average retail price of $27.77, according to GoodRX, and Medicare and most major insurance plans cover it. A three-year retrospective study of United Health Care members, which was published in April 2015 in the Annals of Internal Medicine, found only 3.7 percent of those with prediabetes were being prescribed the drug. Fewer than 1 percent of American adults with prediabetes actually took metformin to manage it, according to an article published in July 2017 in Diabetes Care. RELATED: American Diabetes Association Releases 2019 Standards of Care Still, there’s another aspect to a prediabetes diagnosis to consider: the effect it can have on the person living with it. “If they are labeled with that, rightly or wrongly, it creates a whole Pandora’s box of things,” says Bandukwala. “Some patients freak out for a variety of reasons. They may have family members or friends that they have seen struggle with amputation or heart disease or kidney failure. You name it. And then they may also have that concern about what is being put on their chart: ‘Don’t put that I’m diabetic because my insurance might ding me or my job may view me differently.’” Don’t panic, says Bandukwala. “You’re going to be okay. It’s just a number, so we can follow it, we can measure it again, we can talk about diet and exercise.” Keep calm, and do the following:
Ask your primary care doctor about what you can do to lower your risk of progressing to diabetes, including eating a healthier diet and exercising more.Look up whether there’s a National Diabetes Prevention Program available in your community.Seek a referral to a registered dietitian nutritionist in case you may benefit from changing your eating habits.
Above all, no matter your stance on the definition of prediabetes, keep your diagnosis in perspective. “This doesn’t mean you have diabetes or that you are going to get diabetes,” says Bandukwala. It’s simply a warning sign to make changes.
