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.
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.
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
OGTT (2 hours)
6.5% or higher
126 mg% or higher
200 mg% or higher
5.7% to 6.4%
100 to 125 mg%
140 to 199 mg%
5.7% or less
99mg% or less
140 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.
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.
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.
The mission of the The Thyroid Project is to encourage sharing of information and experience between the public and the medical community about the treatment of hypothyroidism (low thyroid function). For at least the past few decades there is a growing awareness of â€œsomething missingâ€ in the way suffers of hypothyroidism are treated for their disease.
Too many patients, as documented in an on-line study of 12,000 individuals conducted by the American Thyroid Association published in June 2018, (https://doi.org/10.1089/thy.2017.0681) , complain of persistent symptoms of hypothyroidism despite what their doctors believe is successful treatment with levothyroxine (brands include Synthroid, Unithroid, Tirosent, Levoxl). We believe something needs to be done to resolve this conflict between patients and their doctors.
Diabetes can be defined simply as elevated blood sugar levels. What exactly is high blood sugar and when should someone be concerned about their level? Does having prediabetes mean diabetes is around the corner? Metabolism.com tackles this tricky but important topic in this comprehensive review.
By Gary M. Pepper, M.D. Ozempic, Rybelsus, Trulicity, Wegovy, Saxenda are the central players in the weight loss craze sweeping across the globe. Metabolisim.com has been monitoring this phenomenon from its beginnings in 2008 with its report “Lizard Spit Reduces Blood Sugar and Appetite”, regarding the first drug in this class, Byetta (exenatide). Caught In the middle of the current chaos are the medical experts who treat diabetes and have been prescribing these medications for more than a decade. Here is a brief commentary from one such board certified endocrinologist; “I started treating Type 2 diabetics with GLP-1 agonists more than 10 years ago. In some respects, these medications have revolutionized the treatment of diabetes by lowering blood sugar effectively and promoting weight loss at the same time, a unique combination of benefits. Not everyone benefits from these drugs to the same degree unfortunately, and I have seen lots of patients experience unacceptable side effects from them. Nothing though, has prepared me for what is happening now. Too often, I find myself confronting someone who expects me to prescribe one of these drugs just so they can lose weight. Sadly, one extreme example was someone who, despite battling a life threatening medical condition, was insistent on getting a prescription. At the same time my diabetic patients are scrambling to find a place to buy their medications if they can even afford it. It is disheartening, to say the least, and I dread the negative interactions with some of my patients I now face almost daily.”
Off- Label Use
The FDA is the U.S. government’s department tasked with evaluating and approving drugs for specific medical conditions. When a new medication is approved for treating a medical condition by the FDA the agency will, at the same time, set strict guidelines for exactly which patients may use the newly approved drug. When a medication is used “off-label” it means that these limitations are being overridden by the provider for a potential benefit which outweighs the drugs risks. It is a general misconception that off-label means illegal; it does not. This practice has been going on for ages and more than 20% of prescriptions in the United States are prescribed off-label. A common example is the use of beta-blockers (approved for heart problems) for the treatment of performance anxiety.
GLP-1 agonist drugs, as discussed recently by metabolism.com. were originally approved for the treatment of Type 2 diabetes in adults. In the past few years most of these same medications have gained unprecedented popularity for their “off-label” weight loss benefit. Of the 5 GLP-1 agents presently in U.S. pharmacies only Wegovy (semaglutide) and Saxenda (liraglutide) are FDA approved for treating obesity. Of these two, Wegovy is the newer and had been much more popular that its sister drug Saxenda, probably due to being dosed only once weekly compared to daily for Saxenda and less likely to cause side effects. Due to Wegovy’s soaring popularity, its manufacturer, Novo Nordisk, increased the price of Wegovy two times since its initial release.
by Gary M. Pepper, M.D. and Sam Jeans, MSc The global anti-obesity drug market, in 2021was valued at over $2 billion. Within one year this figure had skyrocketed to $8 billion and is expected to climb to nearly $ 20 billion by 2027. This astounding growth is a reflection of soaring obesity rates, and the arrival of a new class of weight loss medication fueling a craze both in the USA and across the world.
The FDA and global health regulators, until very recently, had maintained a very tight ship when it comes to treating obesity with medication, placing the emphasis on diet and exercise rather than weight loss drugs. Since the 80s, anti-obesity drugs continued to be controversial, and a more stringent FDA implemented ongoing safety trials along with other precautions. There is some speculation that a shift in attitude toward approval of weight loss medication by the FDA , is underway
Weight loss drug controversies are far from over and, in fact, may soon rival the amphetamine crisis of the 70’s. For that reason, metabolism.com has felt it important to provide our guide to weight loss drug issues, past and present.
Anti-Obesity Drugs Timeline
Prescription drugs for lifestyle diseases such as obesity were marketed heavily throughout the 1950s to the 1970s. Amphetamines entered the public domain after the Second World War where they were used extensively in the military.
In the 50s, walk-in clinics prescribed diet pills with other medications almost at random, with or without genuine concern for one’s weight. These brightly colored pills became known as “rainbow pills”.
In the 1960s and 1970s, the so-called “rainbow pill diet” of pills was finally coming to an end as the FDA began to systematically ban many of the drugs involved. A high-profile expose by investigative journalist Susanna Mcbee, published in Life magazine, brought attention to this new modern public health crisis.
The rainbow pill diet combined amphetamines, laxatives, thyroid hormones, and even diuretics to produce extreme weight loss, combined with benzodiazepines, barbiturates, and steroids to reduce side effects, and antidepressants to suppress medication-induced insomnia and anxiety.
In 1968, rainbow pills were linked to over 60 deaths, with numerous accounts of their devastating impact surfacing in the news and media. Within just two months, 48 million pills were seized and destroyed. Nevertheless, amphetamine-based diet pills remained extremely popular throughout the 1970s. In 1978, some 3.3 million prescriptions for amphetamines were written each year, with some 50 million pills a year ending up in the black market.
In 1979, the FDA banned amphetamines as a weight loss aid, but that is hardly the end of the USA’s love affair with obesity medication.
Here’s a brief timeline of recent anti-obesity drugs: