Prediabetes: Non-Diabetic Hyperglycaemia and How to Reverse It

Introduction

Prediabetes describes blood glucose that is higher than normal but below the threshold for diabetes. It represents the intermediate stage of a continuum: insulin resistance has developed, beta cells are compensating, and glucose has begun to drift upwards - but the compensation has not yet failed.

NICE deliberately avoids the term prediabetes, preferring non-diabetic hyperglycaemia or describing people as being at high risk of type 2 diabetes.¹ The reasoning is worth understanding: prediabetes implies an inevitable progression to disease, which is not what happens. A substantial proportion of people revert to normoglycaemia, particularly with weight loss, and labelling someone as pre-diseased can be both inaccurate and demoralising.

Around one in ten UK adults has non-diabetic hyperglycaemia, and the great majority are unaware of it. It is asymptomatic by definition, so it is found only by looking for it.

Who to test

NICE recommends a two-stage approach: identify risk with a validated tool, then confirm with a blood test.¹

Stage 1 - risk assessment

• Validated risk tools - the Leicester Practice Risk Score or QDiabetes applied to practice records, or the Diabetes UK Know Your Risk self-assessment
• The NHS Health Check - offered to adults aged 40 to 74 every 5 years
• Risk scores combine age, sex, ethnicity, BMI, waist circumference, family history, blood pressure and drug history

Stage 2 - blood testing

Offer a blood test (HbA1c or fasting plasma glucose) to anyone identified as high risk. Specifically consider testing:

• Adults aged 40 and over, and from age 25 in people of South Asian, Chinese, African-Caribbean, Black African and other high-risk minority ethnic backgrounds
• BMI 25 or above, or 23 or above in South Asian and Chinese populations, with any additional risk factor
• Previous gestational diabetes - test annually, since around half develop type 2 diabetes within 10 years
• Established cardiovascular disease, hypertension or dyslipidaemia
• Polycystic ovary syndrome
• A first-degree relative with type 2 diabetes
• Severe mental illness, particularly on antipsychotics such as olanzapine or clozapine - test at baseline and annually
• Long-term corticosteroid treatment
• Metabolic dysfunction-associated steatotic liver disease

Why it matters

Progression to diabetes

• 5 to 10% of people with non-diabetic hyperglycaemia develop type 2 diabetes each year
• Risk of progression is highest with impaired glucose tolerance, with HbA1c in the upper part of the range (45 to 47 mmol/mol), with obesity, and where both fasting and post-load glucose are abnormal
• Reversion to normoglycaemia is common, occurring in a substantial minority - particularly with weight loss - and is associated with a reduced long-term risk of diabetes

Risk that is already present

The diabetes threshold is a statistical convention, not a biological cliff, and harm begins below it.

• Cardiovascular risk is raised before diabetes is diagnosed - roughly 10 to 20% higher for cardiovascular events, and the association is strongest for impaired glucose tolerance
• Microvascular change can already be present - retinopathy is detectable in a small proportion of people with IGT, and distal sensory neuropathy is more common than in normoglycaemic controls
• Chronic kidney disease and metabolic dysfunction-associated steatotic liver disease cluster with it
• The practical implication is that non-diabetic hyperglycaemia should prompt assessment and management of the whole cardiovascular risk profile, not simply a repeat blood test in a year

Management

Intensive lifestyle-change programme

This is the first-line intervention and the one with the best evidence. In England it is delivered as the NHS Diabetes Prevention Programme (Healthier You) - a structured, group-based programme of at least 13 sessions over a minimum of 9 months, covering diet, physical activity and behaviour change, with a digital option available.²

Drug treatment

• Metformin - consider it where HbA1c or fasting glucose is deteriorating despite an intensive lifestyle programme, or where the person is unable to take part in such a programme. Start at a low dose (500 mg daily) and titrate over several weeks towards 1500 to 2000 mg daily as tolerated. Monitor HbA1c or fasting glucose every 3 months while titrating. This is an off-label use and should be discussed as such.
• Orlistat - consider alongside lifestyle measures in people with a BMI of 28 or above, as part of an overall weight management plan
• Do not routinely offer other glucose-lowering drugs for prevention outside a trial setting, although GLP-1 receptor agonists licensed for obesity will reduce progression as a consequence of weight loss
• Manage the wider cardiovascular risk - calculate QRISK3 and offer a statin where indicated, treat hypertension, and support smoking cessation. These reduce more events than the glucose intervention itself.

Monitoring and follow-up

• Repeat HbA1c or fasting glucose at least annually, and more frequently in those at highest risk or on metformin
• Reinforce lifestyle advice at every contact, and re-refer to a prevention programme if risk factors worsen
• Measure weight, blood pressure and lipids at review
• Tell people what to look out for - thirst, polyuria, weight loss, fatigue and recurrent infection - and to seek testing sooner if they appear
• Record it in the notes and on the practice register, so the annual recall actually happens. Failure of follow-up is the commonest reason opportunity is lost.

Specific situations

After gestational diabetes

• Offer a fasting plasma glucose 6 to 13 weeks after birth, or an HbA1c after 13 weeks
• Annual HbA1c thereafter, lifelong, because around half develop type 2 diabetes within 10 years
• Offer lifestyle advice and referral to a prevention programme, and discuss preconception testing before any future pregnancy
• Breastfeeding reduces future maternal diabetes risk and is worth mentioning

Steroid-induced hyperglycaemia

• Corticosteroids raise glucose predominantly after lunch and in the afternoon and evening with prednisolone taken in the morning, so a fasting glucose or HbA1c may be normal and miss it
• Check random or post-lunch capillary glucose in patients on significant steroid doses
• Monitor during and after courses, and remember that hyperglycaemia may persist after the steroid is stopped

Severe mental illness and antipsychotics

• Olanzapine and clozapine carry the highest metabolic risk
• Check weight, HbA1c and lipids at baseline, at 3 months and then annually
• This group has a markedly reduced life expectancy driven largely by cardiovascular disease, and is systematically under-screened - a genuine health inequality worth acting on

Red flags

Prognosis

The natural history of non-diabetic hyperglycaemia is genuinely variable, and this is the most important thing to convey. Around a third of people progress to type 2 diabetes within 5 years if nothing changes, roughly a third remain in the prediabetic range, and a meaningful proportion revert to normal glucose regulation - reversion being commonest in those who lose weight and in those with an HbA1c at the lower end of the range.

Where intervention is delivered, the effect is large and durable. Structured lifestyle programmes roughly halve the rate of progression, the benefit persists for decades after the programme finishes, and long-term follow-up of the Da Qing cohort showed reductions not only in diabetes but in cardiovascular events, microvascular complications and overall mortality.

Cardiovascular risk is the element most often overlooked. Because that risk is already elevated at the prediabetic stage, the value of identifying these patients lies as much in treating blood pressure and lipids and supporting smoking cessation as in preventing the diabetes itself. In practice, a patient identified with non-diabetic hyperglycaemia should leave the consultation with a prevention programme referral, a cardiovascular risk assessment and a date for a repeat test - and the accurate reassurance that this outcome is far from fixed.