It's hard to know how to think about prediabetes, a condition in which a person's blood sugar level is higher than normal but not high enough to qualify as full-blown diabetes. On the one hand, many people with prediabetes go on to develop diabetes, which is now the seventh-leading cause of death in the United States — but on the other hand, most don't. Indeed, the condition is — paradoxically — both underdiagnosed and overdiagnosed, researchers say.
Confused? You're not alone. A 2019 survey of primary care physicians showed they have limited knowledge about which patients should be screened for prediabetes, how to read lab tests to diagnose it and what to advise patients who are diagnosed.
One reason may be that five definitions — based on three types of blood-sugar tests — are in use in the United States, says Elizabeth Selvin, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health. In a recent article in the Annual Review of Public Health, Selvin and a colleague argued that the multiple definitions may explain why physicians might be uncertain about whether or how to act on screening results. The vast majority of people who have the condition are unaware of it, according to the US Centers for Disease Control and Prevention.
"When you don't have consensus in the field of how to define something, how to diagnose it, and what to do, I think that creates a lot of confusion," she says.
The picture isn't getting any clearer, either. Emerging research suggests that high levels of blood glucose are not the whole story for prediabetes. An international research team recently identified six subtypes of prediabetes — three serious and three less so — that may provide new insight into why the condition affects individuals differently.
"Glucose is one problem, sure, but there's a constellation of different factors," says the study's first author Robert Wagner, an endocrinologist at the Tübingen University Hospital in Germany. "The glucocentric paradigm — that glucose is the most important thing — is changing."
Much more research is needed to turn these findings into information doctors can use. For now, this is the bottom line: Many Americans meet the criteria for prediabetes, and some of them need to take action to avoid serious problems. Research has proved that prediabetes can often be eliminated with weight loss, a healthy diet and exercise.
Here's what we know about prediabetes, its diagnosis and treatment.
What Exactly Is Prediabetes, and How Common Is It?
A person with prediabetes has a blood sugar level higher than normal but not high enough to meet the criteria for diabetes. But what constitutes "normal" is open to debate.
The American Diabetes Association, the World Health Organization (WHO) and a joint body called the International Expert Committee, made up of members from three diabetes organizations, have developed five definitions of prediabetes. The various definitions reflect three different ways of testing blood sugar levels and different cutoffs for diagnosis.
That means that a person could have "normal" blood sugar under the WHO definition but be diagnosed with prediabetes under the American Diabetes Association definition. "The various tests identify different people and have only moderate overlap, meaning that some people will be classified as having prediabetes by one definition but not by another," Selvin and her colleague wrote.
The prevalence of prediabetes depends on which definition is used. The WHO and the International Expert Committee use more stringent definitions, which highlight those who are most likely to progress to diabetes. The American Diabetes Association uses lower thresholds, so it identifies a larger number of patients. Some diabetes experts have been railing against the ADA's definition of prediabetes for many years, saying it diagnoses far too many people who may not need treatment.
By lowering the threshold for a prediabetes diagnosis, the ADA at least doubled the number of people meeting prediabetes criteria compared to previous estimates, including "a whole heterogeneous bunch of people who've got a mishmash of different sorts of abnormalities in their glucose tolerance," said John Yudkin, a clinical diabetologist at University College London, in a 2014 interview.
The CDC sees it differently, counting anyone who meets the ADA's generous thresholds on either of two different tests. This leads them to estimate that 88 million American adults — more than one in three — have prediabetes, although many fewer — about one in 10 — meet the criteria for prediabetes based on both those tests.
Why Is Prediabetes Important?
Prediabetes is important because diabetes is important. An estimated one-tenth of US adults — 34.2 million people — have diabetes, and the CDC expects that to rise to one-third of adults by 2050. A small minority of those have type 1 diabetes, an unpreventable autoimmune condition usually diagnosed in childhood. But at least 90 percent have type 2 diabetes, in which the body's cells become less responsive to insulin, so that the pancreas can no longer produce enough to regulate blood sugar properly over time. Though the metabolic processes that underlie the condition are not fully understood, being overweight and inactive are significant risk factors.
The toll of poorly managed type 2 diabetes is dire: heart disease, blindness, kidney failure, strokes and amputations. The disease is not curable, although treatments such as gastric bypass surgery can put it into remission for many years. But type 2 diabetes is often preventable. Before people acquire the disease, they typically spend several years in the prediabetes state. About 5 to 10 percent of these people will progress to diabetes every year. But others may never progress: Up to 59 percent of people diagnosed with prediabetes may spontaneously return to normal blood sugar levels within five years, studies show. The problem is that doctors don't yet have a way to predict who will progress to diabetes and who will not.
Is Prediabetes Itself Serious?
A diagnosis of prediabetes is a warning, says Prakash Deedwania, a cardiologist at the University of California San Francisco. "It's almost saying that you have a deadly disease around the corner and you can do something about it now or suffer the consequences." By the time someone develops full diabetes, irreversible damage to a person's arteries, kidneys and other organs may have already begun, research shows.
And even before that happens, people with prediabetes may have more medical problems than their peers who have normal blood sugar. A recent study of more than 25,000 people in Michigan found that over a 14-year period, those diagnosed with prediabetes were significantly more likely to experience a heart attack or other major cardiovascular event than those with normal glucose levels, although that does not prove that prediabetes caused the heart problems. And prediabetes is associated with increased risk of vascular dementia and cognitive decline, another study found.
On the other hand, many elderly people can ignore prediabetes entirely. "Diabetes is a disease that incurs problems over many, many years," says Kenneth Lam, a geriatrician at the University of California San Francisco. For those who no longer have many years left, doing something about a prediabetes diagnosis may create work that never benefits the patient, he says.
Some other prediabetics may also have little to worry about. The six subtypes reported by Wagner and his colleagues — identified after rigorous testing of 899 people at high risk for diabetes for 25 years — are based not only on blood glucose levels, but also on liver fat, body fat distribution, blood lipid levels and genetic risk.
In three of the subtypes, the risk of progressing to diabetes was low even after all those years. In three others, however, people were at substantial risk. In one cluster, people produced too little insulin; in another, people had a fatty liver and their bodies were resistant to insulin; in another, people were slow to progress to diabetes but they suffered kidney damage before that occurred and mortality was particularly high. The researchers confirmed the six subtypes in a second population, a group of nearly 7,000 civil servants in London.
Some of the tests needed to identify the subtypes — for example, measuring liver fat and genetic profiles — aren't routinely available outside of research studies, so people with prediabetes cannot know for sure if they fall in one of the high-risk groups. But Wagner's work adds support to the idea that visceral fat, which can be estimated by measuring waist circumference, can help indicate diabetes risk, as all three high-risk subtypes had higher levels of visceral fat, while lean people had the lowest risk.
The work needs to be replicated by more studies, says Miriam S. Udler, director of a diabetes genetics clinic at Massachusetts General Hospital, but it offers "exciting potential" to reconsider how prediabetes should be treated. The ability to identify people at higher risk of serious health problems will allow doctors to focus attention on them and assure other people that their prediabetes diagnosis is not a big worry, she wrote in Nature Medicine.
What Should People Do About Prediabetes?
Anyone age 35 to 70 who is overweight should have a blood test to screen for prediabetes, according to the US Preventive Services Task Force, an independent panel of experts that makes recommendations about preventive medical services.
For those diagnosed with prediabetes, doctors can't yet predict whether they will progress to serious illness, so the safe approach is to take action. But many patients don't see it that way, says Joshua Joseph, a physician scientist at the Ohio State University College of Medicine who specializes in diabetes prevention. "Some hear 'Oh man, I'm at really high risk of diabetes,' or they hear 'Oh great — I don't have diabetes so I'm good,'" Joseph says. "Far too much of the time, it's the second one."
That's a mistake, because acting early can make a big difference. A study of more than 3,000 prediabetic Americans found that if a person loses just 5 to 7 percent of their body weight and engages in 150 minutes of moderate exercise a week, they cut their risk of diabetes by more than half. A Finnish study that sought to learn whether modest weight loss — 5 percent of body weight — along with 30 minutes of moderate activity per day and a diet with less fat and more fiber would reduce a person's risk of diabetes was ended early because the evidence that it worked was so clear.
Many other studies showed similar results. In a review of randomized controlled trials, seven of nine studies of people with prediabetes found that "lifestyle interventions" — weight loss, healthy diets and exercise — decreased the risk of diabetes for up to 10 years after the treatment began. That's why metformin, the medication doctors might prescribe for prediabetes, is not doctors' first choice. In a trial that compared metformin with lifestyle change, healthy habits won out. Those who changed their diet and exercise patterns reduced the incidence of type 2 diabetes by 58 percent, while those who took metformin reduced it by 31 percent.
"You begin with simple lifestyle interventions, which are not costly," Deedwania says. "And you can reverse it quite often and prevent the development of diabetes."
Formal Programs Can Help
The Diabetes Prevention Program is an intense yearlong program that helps people lose weight and keep it off while adopting healthy habits. It uses a curriculum, coaching and a support group and requires a big commitment: weekly meetings for the first six months and less frequent meetings for another six months.
The program has been tested for more than two decades in a large clinical trial that started with more than 3,000 people with prediabetes. The first results, published in 2002, showed that people who lost 7 percent of their body weight reduced the risk of developing diabetes by 58 percent. Subsequent studies have shown that participants continue to prevent or delay diabetes for at least 15 years.
Evidence in the original study was strong enough that, in 2010, Congress authorized the Centers for Disease Control and Prevention to establish a public-private effort to offer the Diabetes Prevention Program in communities across the United States.
But many people with prediabetes never hear of the program, let alone participate, Joseph says. A survey of 2,341 individuals who were overweight, obese or diagnosed with prediabetes found that only about 4 percent had been referred to the program, and just over 2 percent had participated.
That may be partly because the Diabetes Prevention Program is typically offered by community organizations like the YMCA or by public health agencies, rather than in the regular health care system. That makes it challenging for doctors to use the program, because they can't refer patients to it through their usual medical record system.
Another barrier is the cost. Medicare covers the Diabetes Prevention Program, but many people who are likely to benefit are younger than 65 and not covered by Medicare. Some, but not all, private insurance companies pay for it.
Paying for treatment to prevent diabetes is much less expensive than paying for a foot amputation or other complication, but the way health insurance works in the United States does not incentivize insurers to pay for prevention, Selvin says. That is because most people do not stay with the same insurance company throughout their lifetime, and a patient untreated for prediabetes today will not suffer expensive complications of diabetes until many years in the future. So from the insurance company's point of view, Selvin says, "there isn't an absolute benefit of prevention if that person is not going to be insured by your plan five years from now."
There's No Downside to Dealing With Prediabetes
Considering that 74 percent of American adults over 20 are overweight or obese, prediabetes — and a slide into diabetes — looms as a potential threat for most of us. Rather than wait for diagnosis, Joseph encourages everyone to work toward a healthy lifestyle that includes getting 150 minutes of physical activity each week and choosing healthy foods. There's also evidence that lowering stress and getting at least seven hours of sleep each night can help.
"These are all things that reduce risk of diabetes, but they aren't really specific just for diabetes," he says. "These things are good for us no matter what conditions we're trying to prevent."
This article originally appeared in Knowable Magazine on November 12, 2021. Knowable Magazine is an independent journalistic endeavor from Annual Reviews, a nonprofit publisher dedicated to synthesizing and integrating knowledge for the progress of science and the benefit of society. Sign up for Knowable Magazine's newsletter.
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