Stopping Prediabetes in Its Tracks: Simple Interventions that Work

By Gary Pepper, M.D. and Sam Jeans MSc

In our previous article The Prediabetes Puzzle: What the Blood Tests Mean, we investigated controversies surrounding diabetes diagnosis.

There’s a clear lack of consensus surrounding thresholds for diagnosis of prediabetes, the tests used to measure blood sugar, and the way forward for those at risk of transitioning from prediabetes to diabetes.

If left untreated, at least 37% of individuals with prediabetes typically develop type 2 diabetes in 4 years. But, with appropriate and early intervention, this can be dramatically reduced to 17% or less.

Here, we’ll investigate what diabetes interventions are effective, including lifestyle changes and medication.

Early Interventions For Prediabetes

Diagnosis of prediabetes is a useful wake-up call for many.

A sedentary lifestyle, a poor diet…these are significant contributors to prediabetes, and fighting back to take back control of one’s health vastly decreases the likelihood of transitioning to diabetes. The earlier prediabetes is caught, the easier it is to tackle.

When prediabetes is diagnosed, people face a series of choices. Should you tackle it with lifestyle changes alone?

Will you stick to the plan for long enough to see the benefits?

Or is early intervention with medication a good idea? And if so, what medication?

The Impact of Diet And Exercise

Unsurprisingly, a healthy diet and exercise are essential for weight management and glycemic control. Sustained lifestyle improvements improve insulin sensitivity, decreasing blood sugar levels and stunting the development of full-blown diabetes.

But how effective are lifestyle interventions?

An influential study of lifestyle interventions, The Diabetes Prevention Program (DPP), demonstrated that a low-fat, low-calorie diet reduced the incidence of diabetes by 58% in individuals with prediabetes.

The study recommended a daily intake of less than 25% of total calories from fat, increased fiber intake, and reduced daily calorie intake to achieve 7% weight loss. It’s worth highlighting that the study involved 1,079 participants and was highly structured with a relatively strict regime of 16 taught sessions. Non-adherent participants were introduced to a “toolbox” of extra interventions.

Another major systematic review found that, after one and three years of lifestyle intervention, the risk of diabetes decreased by 36% to 54% compared to treatment as usual.

Several studies also found a reduced incidence of cardiovascular and microvascular illnesses (e.g., neuropathies). Even when blood sugar levels don’t drop to normal, lifestyle changes were shown to improve overall health and lower the risk of mortality.

Further, multiple studies show that lifestyle exercises are considerably more effective than medication alone:

“Lifestyle intervention decreased the incidence of type 2 diabetes by 58% compared with 31% in the metformin-treated group” The Diabetes Prevention Program (DPP).

In short, it’s certain that lifestyle changes can change the course of diabetes.

However, not everyone has access to targeted diabetes interventions like that provided by the DPP.

Self-led and clinician-supported lifestyle interventions are still effective – here’s what people can do.

What To Do

(Reminder: Any recommendations made here are for educational purposes only. Only your health care provider can prescribe lifestyle modifications or medications appropriate for you as an individual)

Firstly, it’s time to get moving. The American Diabetes Association (ADA) recommends at least 150 minutes of moderate-intensity aerobic exercise per week, with no more than two consecutive days without activity. Resistance training is also recommended at least twice a week if possible.,

In terms of diet, all the usual recommendations apply. Decrease saturated fat, sugar, refined carbs, and calories and swap for protein, fiber, and wholegrains.

Add plenty of fruit, veg, grains, legumes, nuts, and good fats like olive oils. Ditch processed food.

While any lower-fat, lower-calorie diet with plenty of fruit and veg is better than a heavily processed diet, the Mediterranean diet is shown to be particularly effective.

Characterized by high consumption of fruits, vegetables, whole grains, legumes, nuts, and olive oil, the Mediterranean diet performs better than other diets.

5-Step Plan for Reducing Diabetes Risk

Here is a 5-step plan to reduce the risk of diabetes through lifestyle changes:

  • 1. Weight management: Achieving and maintaining a healthy weight is crucial for diabetes prevention. The Diabetes Prevention Program (DPP) found that a modest weight loss of 5-7% of initial body weight significantly reduced the risk of developing type 2 diabetes in individuals with prediabetes. 5 to 7% is achievable for most people.
  • 2. Dietary modifications: Consuming a balanced and healthy diet is essential for diabetes prevention. The DPP recommended a low-fat, low-calorie diet with high consumption of fruits, vegetables, whole grains, legumes, and nuts.
  • 3. Physical activity: Regular exercise helps improve insulin sensitivity and aids in weight management. The American Diabetes Association (ADA) recommends at least 150 minutes of moderate-intensity aerobic exercise per week, with no more than two consecutive days without activity.
  • 4. Quit smoking: Smoking has been associated with an increased risk of developing type 2 diabetes. Quitting smoking can help reduce the risk of diabetes and various other health issues, including cardiovascular diseases and respiratory illnesses.
  • 5. Stress management: Chronic stress has been linked to an increased risk of developing type 2 diabetes. Adopting stress reduction techniques, such as mindfulness meditation, yoga, or engaging in hobbies and relaxation activities, can help manage stress and contribute to overall well-being, potentially reducing the risk of diabetes.

The positive effects of lifestyle changes start quite quickly – within days to weeks.

But, blood sugar levels can take months to years to come down. So, regular check-ups are essential, and don’t become disheartened if the impact isn’t immediate.

Diabetes Medication

Medications remain extremely important in treating diabetes.

Not everyone can commit to the lifestyle changes required to reduce blood sugar levels naturally.

For example, some with prediabetes may be unable to partake in intense exercise due to musculoskeletal issues, disabilities and complications from other diseases. But, of course, that isn’t to say that diet and healthy eating alone won’t have an impact.

The critical issue is, lifestyle interventions often aren’t adhered to for long enough to have an impact. Or in other words, people give up.

Studies place adherence to lifestyle interventions at around 50 to 60%. So over half of people give up in many cases. Those that give up are very likely to develop diabetes without other interventions.

This has led many health authorities to encourage medication almost immediately.

Diabetes Drugs are Changing

Diabetes medications remained fairly consistent for almost 50 years.

Metformin and thiazolidinediones (formerly known by the brand name Actos), in particular, have been considered highly reliable in treating diabetes.

There’s been an explosion in new diabetes drugs in recent years, with the 50-year-old metformin, although remaining the first choice, this dominance has been challenged in the last few years.

Newer peptide-1 (GLP-1) agonists (e.g., semaglutide/liraglutide with brand names like Victoza and Ozempic) and SGLT-2 inhibitors such as Jardiance and Invokana have grown in interest for their ability to lower blood sugar levels and reduce weight. While their performance for reducing blood sugar are very similar to older drugs, they may have a better combined impact on blood glucose and weight loss.

There’s an all-too-familiar issue at play, though. Liraglutide and semaglutide drugs are expensive.

An article published in the Wall Street Journal sums this up well, “The newer drugs cost more than metformin, however, and some patients might not be able to afford the out-of-pocket costs and need to go with metformin. Ozempic, for example, lists for nearly $900 a month, and Jardiance comes in at about $590 a month.”

So, what does this all mean for metformin and other diabetes drugs? Will they merely fade into the background?

Metformin: Still a Wonder Drug?

Metformin is still the world’s most widely used medication for treating type 2 diabetes and has demonstrated efficacy in preventing the progression from prediabetes to diabetes.

Metformin primarily reduces glucose production by the liver and increases insulin sensitivity in peripheral tissue.

The DPP revealed a 31% reduction in the incidence of diabetes in individuals with prediabetes treated with metformin compared to the control group. While combined metformin and lifestyle change was significantly more effective at 58%, metformin’s impact is still impressive.

The drug is generally well tolerated, with gastrointestinal side effects being the most common adverse events. Some patients do experience lower exercise tolerance after taking metformin, which may impede exercise interventions, but evidence suggests this is minimal in most cases. Metformin has been around for a long time, and there’s not much we don’t know about it – no nasty surprises means a lot. Furthermore, metformin costs pennies per month making the overall appeal of this drug for diabetes management almost unchallengeable.

However, despite its excellent safety and tolerability profile, we can see early indications that pharma is falling out of love with the drug.

Some 80% of those with diabetes are eligible for new drugs, according to this publication by WebMD. The report emphasizes Ozempic, which currently costs $814 to $1040 per month.

Indeed, higher profit margins on new drugs are hardly discouraging pharma from thrusting semaglutide/liraglutide into the limelight.

Another Contender: Pioglitazone

Another veteran diabetes drug, pioglitazone, originally marketed as Actos, has also demonstrated efficacy in preventing the progression from prediabetes to diabetes.

It works by increasing insulin sensitivity in peripheral tissues and reducing hepatic glucose production.

The ACT NOW study showed that pioglitazone reduced the risk of developing diabetes by 72% in individuals with impaired glucose tolerance – better than metformin and newer semaglutide/liraglutide drugs.

However, concerns that pioglitazone raised the risk of heart failure and carried a small risk of bladder cancer impacted its reputation in the early-2000s.

Pioglitazone: Dangerous or Disregarded?

A few studies have drawn attention to pioglitazone’s controversial status in diabetes treatment.

● One such 2014 article Pioglitazone: An Antidiabetic Drug with Cardiovascular Therapeutic Effects, concluded that pioglitazone has beneficial effects, contrary to some earlier concerns about its safety. In addition, they draw attention to the 2005 PROactive study, which demonstrated that pioglitazone reduced non-fatal myocardial infarction and stroke in patients with type 2 diabetes.

● Studies in 2007 and 2013 both encouraged new insights into the drug, the latter, published in the journal Diabetes Care, suggesting “more commonly used regimens (other than pioglitazone) are both less effective and more likely to result in worse safety outcomes.” The authors also address the concern of an increased risk of bladder cancer associated with pioglitazone use, stating that the evidence is inconclusive and the absolute risk, if any, is low.

● In 2021, another study Rethinking pioglitazone as a cardioprotective agent: a new perspective on an overlooked drug , further highlighted pioglitazone’s cardiovascular benefits, such as reducing the risk of major adverse cardiovascular events in certain patient populations.

As the pharmaceutical industry slowly shifts the emphasis to newer, more expensive peptide-1 (GLP-1) agonists and SGLT-2 blockers, it’s essential to remain mindful of longstanding, reliable drugs with well-understood safety profiles.

Pioglitazone and metformin are exceptionally well known to medical science. Although some practitioners imply that these older medications have become outdated, their long record of safety and efficacy should be a major plus when considering treatment options.

Summary: Preventing the Progression from Prediabetes to Type 2 Diabetes

Preventing the progression from prediabetes to diabetes is critical. This important window of intervention shouldn’t be ignored.

Evidence-based strategies, including weight management through diet and exercise and the use of medications such as metformin, pioglitazone, and newer agents such as Ozempic , can significantly reduce the risk of developing diabetes in individuals with prediabetes.

Lifestyle changes are extremely effective and can have a transformative effect. People must stick to them – don’t be part of the 50%+ of those who give up.

When it comes to medication, old is still sometimes gold. Newer medications may grab the headlines (and advertising time), the reliability and affordability of older medications like metformin should not be overlooked

Disclaimer; This publication/article, as well as all publications originating at www.metabolism.com,  is/are for the sole purpose of information and education and not intended as medical treatment or advice or in anyway to substitute for the care rendered by a personal healthcare provider. We acknowledge that in the rapidly evolving field of medical science and treatment, our publication may contain unintentional informational gaps and inaccuracies. If so, we appreciate feedback on these deficiencies so we may correct them. Only your personal health care provider can supply treatment and advice suitable for your needs. Users of www.metabolism.com understand that their use of the website is governed by the disclaimer and terms of use found at www.metabolism.com.
The Prediabetes Puzzle: What the Blood Tests Mean

The Prediabetes Puzzle: What the Blood Tests Mean

by Gary M. Pepper, M.D. with Samuel Jeans, MSc

As an endocrinologist, I frequently encounter patients who are confused about whether they have diabetes or prediabetes. Many have been told that their blood sugar levels were above normal on recent blood tests, possibly indicating prediabetes. However, this concern is often unfounded. So why is this scenario so common?

I believe that commercial lab facilities are partially responsible. Their routine procedure is to flag blood sugar levels over 99 mg% as abnormally high, which can result in many false positive diagnoses of abnormal glucose metabolism. But why do medical facilities continue to follow this protocol?

To understand this, let’s take a closer look at how prediabetes and diabetes are diagnosed.

Diabetes type 2 is a metabolic disease in which the body’s insulin production and sensitivity is impaired, resulting in consistently higher-than-normal blood glucose levels.

At current estimates, between 1 in 10 and 1 in 11 of the world’s population have diabetes.

Around 90% of those who have diabetes have type 2 diabetes.  This is a disease in which the body is able to create insulin but either can’t create enough insulin or has become resistant to it. Insulin helps move glucose (sugar) from the blood into the cells that need it for energy. Diabetes complications include nephropathy (kidney), retinopathy (eye), and vascular disease. In the worst cases, this can lead to complete loss of feeling in the feet, kidney failure or blindness.

The complications of diabetes grow worse with age. At age 50, those with diabetes live six years less on average than those without, according to the CDC. However, early intervention and proper treatment have been shown to restore life expectancy to close to normal levels – especially if prediabetes is identified early.

It’s certainly possible to prevent, delay or change the course of diabetes. However, this depends on a robust and accurate assessment of prediabetes and the timely prescription of medication and lifestyle interventions.

Defining Prediabetes

People don’t become diabetic overnight. Before diabetes is established, individuals go through a stage of prediabetes that can last anywhere between 2 to 5 years. The effects of prediabetes are largely asymptomatic or invisible, and it’s often flagged on coincidental or routine blood tests.

The CDC estimates that 96 million adults in the US – over a third of the population – likely have prediabetes. Similar levels are observed across other developed countries.

In the USA, incidence rates of diabetes have doubled in the last 20 years, and diabetes is the 7th leading cause of death, and this is likely underreported.

Harvard Health cites that many people totally miss prediabetes or don’t take sufficient action to prevent it from developing into full-blown diabetes. As few as 10% of people with prediabetes are aware that they have it. Around 5 to 10% of cases of prediabetes convert into diabetes annually.

On the positive side, lifestyle changes can prevent as many as 70% of cases of prediabetes from turning into diabetes. As such, accurate and timely diagnosis and intervention are a top priority. But as ever, it isn’t as straightforward as some perceive.

Testing and Diagnosing Prediabetes and Diabetes

Testing blood glucose levels and response is critical for diagnosing prediabetes, as prediabetes is usually asymptomatic and neurologic and vascular pathology are absent.

Recommendations for who and when to screen for diabetes and prediabetes have been provided by several authoritative organizations and are summarized by metabolism.com in an earlier article.

However, capturing blood glucose levels and robustly diagnosing prediabetes is challenging, and leading health authorities provide varying and non-consistent advice.

There are four main ways to test and measure blood glucose to diagnose prediabetes and diabetes. Here’s an overview of each:

1: HbA1C Test

The HbA1C test (glycosylated hemoglobin A1c) measures average blood sugar level over a long period, typically the past 2 or 3 months. It achieves this by measuring the amount of hemoglobin in the red blood cells coated with glucose (HbA1c).

An HbA1C below 5.7% is considered normal, between 5.7 and 6.4% indicates prediabetes, and 6.5% or higher indicates diabetes.

2: Fasting Blood Sugar Test

A fasting blood sugar test measures impaired fasting glucose (IGT). The blood test is taken after an overnight fast (not eating).

The American Diabetes Association defines a fasting blood sugar level of 99 mg/dL or lower to be normal, 100 to 125 mg/dL indicates prediabetes, and 126 mg/dL or higher indicates diabetes.

3: Glucose Tolerance Test

Glucose tolerance tests measure impaired glucose tolerance (IGT). This blood test measures your blood sugar before and after drinking a solution containing glucose. The WHO advises that the test is taken 2 hours after ingestion of 75 g of oral glucose.

Additional measurements may be taken at 1 and 3 hours or at 30 to 60-minute intervals. Similarly to a fasting blood test, individuals must fast overnight before the test.

At 2 hours, a blood sugar level of 140 mg/dL or lower is considered normal, 140 to 199 mg/dL indicates prediabetes, and 200 mg/dL or higher indicates diabetes.

4: Random Blood Sugar Test

In some cases, clinicians may choose to take blood sugar randomly, known as a random blood sugar test. This is taken at any point, with no fasting.

It’s not robust but indicates diabetes with a blood sugar level of 200 mg/dL or higher. This often initiates other blood investigatory tests for diabetes.

Diagnostic Criteria for Diabetes vs Prediabetes

Hb A1c Fasting glucose   OGTT (2 hours)
Diabetes6.5% or higher126 mg% or higher200 mg% or higher
Prediabetes5.7% to 6.4%100 to 125 mg%140 to 199 mg%
Normal5.7% or less99mg% or less140 mg% or less

Debates Surrounding Diabetes Diagnostics

Measuring glucose levels is one thing, but relating findings to prediabetes on a patient-by-patient basis is another.

First off, there are four tests to choose from, and global health authorities don’t advise the same test, let alone the same test result criteria.

● The World Health Organization (WHO) defines prediabetes with two parameters. First, they use impaired fasting glucose (IFG), defined as 6.1-6.9 mmol/L (110 to 125 mg/dL). Secondly, they use impaired glucose tolerance (IGT), defined as 2 h plasma glucose of 7.8-11.0 mmol/L (140-200 mg/dL).

● The American Diabetes Association (ADA) uses the same cut-off for IGT but a lower cut-off for IFG (100-125 mg/dL). The hemoglobin A1c test is common in the US, with 5.7% to 6.4% indicating prediabetes.

Then, there are debates surrounding the efficacy and reliability of the tests and their ability to corroborate results. For example, a review of prediabetes found evidence of poor correlation between A1C, IFG and IGT results.

Controversy Surrounding the HbA1C Test

The HbA1C test has come under particular scrutiny. This study in the American Journal of Medical Sciences found that the HbA1C test was poor at predicting prediabetes and that clinicians should refer patients for additional oral glucose testing.

Other findings suggest a strong genetic component in HbA1C, concluding that it’s inherently imprecise. Similarly, another study in Metabolic Syndrome and Related Disorders concluded: “It is important to consider that HbA1c values below 6.5% (for diabetes) and 5.7% (for prediabetes) do not reliably exclude the presence of diabetes and prediabetes, respectively.”

Since the A1C test measures glycated hemoglobin (HbA1c), it’s vulnerable to a myriad of factors affecting HbA1c lifespan and function.

Adding another twist to the debate is a study published in March 2023 which found that the HbA1c test was superior to the IFG (impaired fasting glucose) test for predicting severe diabetic complications, in this case adverse cardiovascular outcomes, in vulnerable individuals.

Contradictions in the Literature

To further salt the wound, evidence surrounding the testing and diagnosis of prediabetes is often contradictory.

● For example, this study from the American Journal of Hypertension says: “The combination of FPG and HbA1c is a reasonable alternative to the generally recommended OGTT for the screening of diabetes”. The authors found the use of the OGTT as the gold standard warrants skepticism.

● Whereas, this one in the American Journal of Medical Science says, “Patients with HbA1c of 5.7% to 6.4% should undergo OGTT to confirm diagnosis of dysglycemia.” The authors reinforce the OGTT as the gold standard.

IGT and IFG are also affected by those who are hypoglycemic, anemic, exhibit altered hematocrit (percentage of red blood cells in the blood), and hypotensive. As such, this study published in Clinical Chemistry and Laboratory Medicine found poor replicability for both of these tests, advising caution for interpreting a single test result.

To further muddy the waters, test conditions are highly influenceable. For example, we know that, for example, eating dinner early improves 24-hour blood glucose levels. Fasting overnight after eating salads all day is likely more favorable for a fasting glucose test than fasting overnight after consuming sodas and fast food all day.

Hormones concentrations in the morning, the “Dawn Phenomenon,” can also affect test results, particularly in those with hormonal conditions. The Dawn Phenomenon is a normal hormonal reflex which increases blood sugar levels in the early morning. For most, this peaks around 3 am to 4 am, but it can extend to 8 am for some, which may feasibly impact glucose test results.

Moreover, diabetes tests often use subsidized rapid test strips with short expiry dates. They’re also affected by variables like temperature, humidity, and quality of blood samples, with error rates of around 12 to 15% in some cases.

In summary, the evidence suggests prediabetes diagnosis is highly sensitive to diagnostic and individual factors.

A review of prediabetes published in the World Journal of Diabetes concludes, to this effect, “the criteria used to define prediabetes needs to be refined in accordance to the long-term medical outcomes.”

Prediabetes Diagnosis: An Opportunity for Positive Change?

Prediabetes screening and diagnosis are becoming more common worldwide, but this presents new challenges for clinicians and health management.

For example, in the UK, the national rollout of the new Diabetes Prevention Programme (DPP) has vastly increased the number of people diagnosed with prediabetes. Clinicians are now raising concerns about the tests and criteria used to define prediabetes and also the social ramifications of creating a ‘new disease’ that may cause depression, anxiety, and stigma.

Harnessing prediabetes diagnosis for positive change is essential. That includes establishing clear guidelines for testing, effectively communicating results with patients, and establishing personalized treatment strategies.

Among all of this, there is at least one positive thing about prediabetes: it’s reversible.

Lifestyle changes such as diet and exercise can reduce risk by 40% to 70% or more, with the added bonus of reducing risk factors for numerous other diseases and disorders.

Stay tuned for our next article to learn about changing the course of prediabetes.

Getting the Right Amount of Sleep Helps Prevent Diabetes

One aspect of lifestyle that is often overlooked is time spent sleeping. Getting adequate sleep is often sacrificed due to the demands of job and family. In the Sleep Heart Health Study over 1400 men and women were surveyed about their sleep habits and its relationship to diabetes and prediabetes. It was found that sleeping less than 6 hours per night was associated with increased risk of having diabetes. Interestingly, in those sleeping more than 9 hours per night there was an increased risk of diabetes and prediabetes.The authors of the study recommend trying to get between 7 and 8 hours of sleep per night to minimize the chances of developing blood sugar problems. To learn more about ways of preventing diabetes see pages 90 to 98 in my ebook “Metabolism.com”

Maintaining ideal body weight with diet and exercise is also crucial for avoiding diabetes and prediabetes.In overweight adults for each2.2 pounds(1 kilogram) gained per year the risk of developing diabetes increases about 50% over the next ten years. By losing 2.2 pounds per year the risk of developing diabetes is reduced about33% for the next 10 years (J Epidemiol Community Health. 2000; 54(8):596-602).

Speak to your healthcare professional to find out if you are at risk for developing diabetes and to learn ways you can avoid it.

Gary Pepper M.D.

Editor-in-Chief, Metabolism.com

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