Examining the value of a prediabetes diagnosis

Several recent studies look at how we define prediabetes, how likely it is to progress to diabetes, and its utility as an early metabolic health warning.

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Recently the U.S. Preventive Services Task Force released draft guidance suggesting that we lower the age we begin prediabetes screening for adults who are overweight or obese from 40 to 35. In doing so, the group cited 2020 CDC statistics that a third of U.S. adults meet prediabetes criteria

The three studies below all deal with core questions around prediabetes as a diagnosis: 

  • How likely is prediabetes to develop into Type 2 diabetes?
  • How do we define prediabetes?
  • Are there negative health consequences to prediabetes even if it doesn’t progress to diabetes?

Before we dive into how researchers answered those questions, it’s worth considering a couple of larger points about prediabetes.

Metabolic health is a spectrum, not an on/off switch. Prediabetes simply means you have a glucose biomarker—typically A1c or fasting glucose—above what is generally considered healthy ranges. But an A1c result of 6.4% (prediabetes) is not meaningfully less dangerous than 6.5% (diabetes). Even below the threshold for Type 2 diabetes, people with higher glucose values may already have some form of insulin resistance (and all the conditions downstream of that), cognitive decline, depression and anxiety, poor skin, erectile dysfunction, cardiovascular disease, and more.

Related article: What should your glucose levels be?

A prediabetes diagnosis is a warning, a chance to examine diet and lifestyle behaviors that can help bring glucose levels down and stave off further damage. That “warning” paradigm is how we view most other cardiometabolic biomarkers: Just because there’s no standard name for cholesterol above a certain level doesn’t mean we dismiss higher-than-average lab results. Instead, your doctor will suggest that you make some lifestyle changes before you need medication. 

Prediabetes is reversible. Multiple studies suggest that lifestyle changes in people with prediabetes can lower glucose levels and prevent the development of Type 2 diabetes. An NIH study showed that people at high risk of diabetes who participated in a lifestyle change program had a 58% lower chance of developing diabetes than a placebo group.

Does a prediabetes diagnosis spur this behavior change? Research is mixed. A 2016 review found that a prediabetes diagnosis “caused a radical change in the way [people] viewed themselves and their health, which was sufficient to make appropriate lifestyle changes.” However, the same review found that many people didn’t fully understand what the diagnosis meant or what lifestyle changes they should make. Research also shows that while the diagnosis can empower some people, it can deflate others. All of this suggests that what’s needed is more education around healthy glucose levels and metabolic behaviors and, as we’ll discuss below, to re-examine the screening and diagnosis for early metabolic dysfunction.    

Is a Prediabetes Diagnosis Useful in Seniors? 

The study: Risk of Progression to Diabetes Among Older Adults With Prediabetes  

What it says: The study began with a group of about 3,400 U.S. adults without diabetes aged 71-90 at the beginning of the study, then looked at outcomes 5-6 years later in the 2,500 who made it to a follow-up visit or died before then.

The study found that prediabetes rates in the group at the outset varied considerably depending on the diagnostic criteria. Using American Diabetes Association (ADA) benchmarks but requiring both HbA1c levels of 5.7%-6.4% and fasting glucose of 100-125 mg/dL produced the lowest incidence at 29%, whereas diagnosing people who had either of those values got the rate up to 73%.

However, overall less than 12% of participants with prediabetes progressed to diabetes in the follow-up appointment. A higher percentage either reverted to normal glucose or died (prediabetes was not associated with a higher death rate). 

Levels Take: This headline is no doubt good news for older adults, and the results mirror those of an earlier Swedish study. The authors conclude, “Taken as a whole, the current evidence suggests that cardiovascular disease and mortality should be the focus of disease prevention among older adults rather than prediabetes progression, especially in the short term (<7 years).”

This conclusion assumes two things: 1) What one focuses on is a zero-sum equation. Many of the diet and lifestyle changes associated with good metabolic health will also help prevent cardiovascular disease. 2) Diabetes prevention is the only worthy goal of a prediabetes diagnosis. Even in older populations, high glucose levels potentially still have consequences, contributing to dementia or loss of physical function [see third study below]. What’s more, maintaining stable glucose levels can have near-term benefits like more sustained energy and reduced anxiety.

So while diabetes progression deserves study (and there is evidence that middle-aged people [30s to 60s] with a prediabetes diagnosis have a higher risk of developing diabetes), it shouldn’t be the only lens through which we evaluate the utility of prediabetes as a diagnosis. Most of us want to be as healthy as possible, rather than simply not sick. 

Prediabetes Outcomes Depend Considerably on Diagnostic Criteria

The study: Lifetime risk to progress from pre-diabetes to type 2 diabetes among women and men: comparison between American Diabetes Association and World Health Organization diagnostic criteria

What it says: This study examined the difference in outcomes between people diagnosed with prediabetes according to the World Health Organization (WHO) criteria, which puts the threshold for fasting glucose at around 108 mg/dL (6.1 mmol/L), and ADA criteria, which has a lower threshold of approximately 100 mg/dL (5.6 mmol/L). The intent was to see if a prediabetes diagnosis identified future cases of diabetes and to look at the differences between men and women. 

To do so, researchers used a population study of more than 8,800 people aged 45 or older in the Netherlands and looked at 10-year and lifetime risk for diabetes diagnosis. 

The study found that both men and women who met the higher WHO benchmark were far more likely to develop diabetes than people at the lower ADA level—for 45-year-old men, for example, the 10-year-risk went from 9% to 25%. Women were significantly more likely to progress to diabetes under either criterion in most age ranges. The ADA criteria more than doubled the number of people who fit a prediabetes diagnosis. 

The lifetime risk numbers were even more striking. The study found that “Approximately half the individuals diagnosed with prediabetes according to ADA-definition and approximately two-thirds of WHO-defined prediabetes at age 45 years would eventually develop diabetes in their remaining life span.”

Levels take: First, this study shows that generally speaking, people with higher glucose levels are more likely to develop diabetes (other studies show even higher rates of progression from prediabetes to diabetes). But the standout finding here is that what constitutes prediabetes is not some preordained number but depends considerably on the criteria and the test. 

The results support those of a 2020 study that compared A1c tests (roughly speaking, your blood sugar average over three months), fasting plasma glucose tests (FPG, a snapshot of your blood sugar uninfluenced by a recent meal), and oral glucose tolerance tests (OGTT, a measure of how your body processes glucose). It found significant differences in outcomes among the tests. FPG and A1c tests, especially when used alone, had very high rates of false outcomes compared to an OGTT gold standard, missing cases of diabetes or misdiagnosing prediabetic people as healthy—results the authors called “catastrophic.” 

This raises another critical point: Glucose alone is too limited a way to screen for metabolic problems. A broader testing regimen should include markers like insulin sensitivity, especially because high glucose is often downstream of insulin resistance. Changes in insulin sensitivity may appear as early as 13 years before a diabetes diagnosis. As your cells become less sensitive to insulin, your body compensates by releasing more insulin, and this can go on for years before glucose levels rise to a prediabetes level. Hyperinsulinemia can cause adverse health outcomes on its own. 

Prediabetes Can Affect Physical Function in Seniors

The study: Not Only Diabetes but Also Prediabetes Leads to Functional Decline and Disability in Older Adults

What it says: This study followed a population of Swedish seniors age 60 and older for as long as 12 years to see how diabetes and prediabetes affected physical function and disability. (Physical function meant ease of standing up from a chair and walking speed, while disability related to the difficulty of doing everyday tasks like grocery shopping, getting dressed, and bathing.)

Researchers found that people with prediabetes, even if they never progressed to diabetes, showed decreased physical function and increased disability. People with diabetes suffered more significant effects.

The study also looked at the development of cardiovascular diseases (CVDs) in the same population and found both diabetes and prediabetes were associated with faster development of CVDs. Researchers believe the presence of CVDs may explain part of the decline in physical function in both groups.

Levels take: This study is helpful in its examination of the effect of prediabetes on physical function in older adults and the role of CVDs. The findings underline the point that even among older adults, the development of diabetes is not the only risk associated with prediabetes—high glucose values can have negative health consequences, even over relatively short time frames. We know that glucose has a relationship with cardiovascular risk, but this takes on additional significance in a population for whom CVD increases mortality risk and potentially affects quality-of-life markers like physical function.