Prediabetes: what it is and how it is managed

If a blood test has shown your blood sugar to be slightly high, or you have heard the word prediabetes, it is normal to have questions. First, to take the drama out of it: prediabetes is not an already established disease, but a state of risk. It is a signal that it is worth taking a calm look, not a definitive diagnosis of diabetes. Here we explain what it is, why it happens and what the evidence says, with all its nuances.

What prediabetes actually is

Prediabetes is the situation in which glucose levels are above normal but do not yet reach the threshold for diabetes. According to the American Diabetes Association (ADA), it is defined by the presence of impaired fasting glucose (abbreviated as IFG), and/or impaired glucose tolerance (IGT), and/or a glycated haemoglobin (HbA1c) in an intermediate range.

These are the three ways of detecting it, with their reference figures:

• Impaired fasting glucose (IFG): fasting plasma glucose of 100 to 125 mg/dL (5.6-6.9 mmol/L).
• Impaired glucose tolerance (IGT): 2-hour glucose after a 75 g oral glucose load of 140 to 199 mg/dL (7.8-11.0 mmol/L).
• HbA1c: values of 5.7 to 6.4% (39-47 mmol/mol).

Any of these three tests (fasting glucose, 2-hour glucose in the oral glucose tolerance test, or HbA1c) is considered appropriate for screening. One useful technical detail: when the oral glucose tolerance test is used, it is important to ensure an adequate carbohydrate intake over the previous three days (at least 150 g a day), because otherwise the result may be distorted.

It is worth pointing out that not all organisations use exactly the same cut-off points. The WHO (1999) and the ADA (2003) agree on the criterion for impaired glucose tolerance (140-199 mg/dL, or 7.8-11.0 mmol/L), but they differ on impaired fasting glucose: the WHO places it at 6.1-6.9 mmol/L and the ADA at 5.6-6.9 mmol/L. That is why, when comparing figures between studies, you need to check which criterion has been used.

Why it matters (it is not just about blood sugar)

One aspect that is sometimes overlooked: prediabetes does not only affect glucose. It is frequently associated with other abnormalities that tend to go hand in hand, such as obesity (particularly abdominal or visceral obesity), dyslipidaemia (high triglycerides and/or low HDL cholesterol) and high blood pressure.

That is why prediabetes is a significant risk factor not only for progression to diabetes, but also for cardiovascular disease and other cardiometabolic outcomes. In fact, detecting it usually prompts a broader assessment of cardiovascular risk factors, not just of blood sugar.

Another important nuance about risk: not everyone with prediabetes has the same level of it. The risk continuum is curvilinear, meaning that as HbA1c rises the risk of developing diabetes increases disproportionately. People are considered to be at very high risk if, for example, they have an HbA1c above 6.0% (>42 mmol/mol), or if they have impaired fasting glucose and impaired glucose tolerance at the same time; in those cases more intensive interventions and closer follow-up are recommended.

How common it is

In Spain, according to the Di@bet.es study, 14.8% of the adult population has some form of prediabetes. That percentage breaks down (using WHO criteria, adjusted for age and sex) into 3.4% with impaired fasting glucose, 9.2% with impaired glucose tolerance and 2.2% with both abnormalities at the same time. Bear in mind that these figures use the WHO cut-off for fasting glucose (110-125 mg/dL), which differs from the ADA cut-off (from 100 mg/dL), so they are not directly comparable with data based on the American criterion. That same study put diabetes at 13.8% of the adult population.

One figure that illustrates why screening matters so much: in the USA, the CDC estimated that in 2015 33.9% of adults had prediabetes according to fasting glucose or HbA1c, and of those only 11.9% reported that a healthcare professional had ever mentioned it to them. In other words, a large proportion of people with prediabetes do not know they have it.

How people at risk are identified

Beyond blood tests, there are tools to identify who should be assessed. The Spanish Diabetes Society points out that screening with the FINDRISC questionnaire (a risk factor questionnaire) and/or fasting blood glucose in at-risk patients makes it possible to pinpoint the people most likely to develop the disease.

And a common point of clarification in consultations: continuous glucose monitoring sensors, those patches that measure blood sugar continuously, are not suitable for screening or diagnosing prediabetes. The ADA notes that there is not enough evidence to support that use.

When prediabetes is already present, the general recommendation is to monitor for the possible onset of diabetes at least once a year.

What the evidence says about how to manage it

This is the more encouraging part. The landmark study is the Diabetes Prevention Program (DPP), which randomly assigned 3,234 people without diabetes to three groups: placebo, Metformin or a lifestyle modification programme (with the aim of losing at least 7% of body weight and doing at least 150 minutes of physical activity a week).

The results spoke for themselves. The incidence of diabetes was 11.0, 7.8 and 4.8 cases per 100 person-years in the placebo, Metformin and lifestyle groups respectively. Compared with placebo, lifestyle change reduced the incidence of diabetes by 58% (95% CI 48-66%) and Metformin by 31% (95% CI 17-43%). Put another way: acting on habits was clearly more effective than the drug.

To get a sense of the benefit in practical terms: to prevent one case of diabetes over 3 years, around 6.9 people would need to take part in the lifestyle programme, compared with 13.9 with Metformin. DPP participants achieved weight losses of 5 to 7%, associated with that 58% reduction in risk.

A very interesting finding for anyone who struggles to lose weight: reaching the target of at least 150 minutes of physical activity a week, even without achieving weight loss, was associated with a 44% reduction in the incidence of type 2 diabetes. Movement counts in its own right.

What is more, the benefit lasts over time. At long-term follow-up (with a mean of 10 years), the incidence of diabetes was still 34% lower in the lifestyle group and 18% lower in the Metformin group compared with placebo.

An honest caveat about the evidence: the effectiveness of these prevention interventions has been demonstrated above all in people with impaired glucose tolerance (IGT), and is not as well established for isolated impaired fasting glucose or for prediabetes defined by HbA1c alone.

On Metformin in prediabetes: transparency above all

Metformin features in the DPP, so it is only natural to ask about it. Here we need to be clear: in Spain, prediabetes is not an authorised indication for metformin. Its summary of product characteristics (AEMPS-CIMA) covers only the treatment of type 2 diabetes mellitus, particularly in people who are overweight, when diet and exercise are not enough; in children and adolescents it also requires the diagnosis of type 2 diabetes to be confirmed before starting.

Any use in prediabetes would therefore be off-label (outside the approved indications). It is also worth remembering that the evidence does not place the drug ahead of habits: in the DPP, lifestyle change was almost twice as effective as Metformin. This article is for information only and does not replace a doctor's decision, as it is the doctor who must assess each individual case.

Key points to take away

• Prediabetes is a state of risk, not a sentence: having prediabetes does not mean you will certainly develop diabetes.
• It is not just about blood sugar: it carries cardiovascular risk and usually comes alongside other factors such as blood pressure, weight and cholesterol.
• The evidence strongly supports lifestyle changes, which have been shown to be more effective than medication in prevention.
• Continuous glucose monitoring sensors are not suitable for diagnosing prediabetes.
• In Spain, Metformin is not authorised for prediabetes.

Everyone is different, and the figures on a blood test only make sense within your own story. If you have been found to have values in the prediabetes range and weight is one of your factors, acting on it is the lever with the best evidence behind it. What exists in Spain today is medical weight-loss treatment, with prior assessment, a prescription where appropriate from a registered doctor and ongoing follow-up. If you want to know whether it fits your case, you can check whether you are eligible.