Why the term ‘prediabetes’ may cause more harm than good

Labelling patients as ‘prediabetic’ may not improve health outcomes because of inconsistencies with the testing and diagnosing of the condition, among other factors, writes Eleanor Barry.

Conceptual artwork of blood glucose test

The term ‘prediabetes’ is an overarching term commonly used to describe people with elevated glucose blood test results but not at the level required to be diagnosed with diabetes. By identifying people with this pre-condition, there is an assumption that we can intervene to stop the progression to diabetes.

However, there is inconsistency internationally in identifying those at risk, with differing criteria being used around the world. Because of limitations with diagnostic tests and inconsistencies between trial and real-world settings, current policies aimed at reducing national diabetes incidence are unlikely to reduce the burden of disease.

The term ‘prediabetes’ is most commonly used in the United States[1]
. In the UK, the National Institute for Health and Care Excellence (NICE), the health technology appraiser, advocates the use of the term ‘non-diabetic hyperglycaemia’[2]
and the World Health Organization uses the phrase ‘intermediate hyperglycaemia’[3]
. The terms have been created in a bid to identify and prevent people from developing type 2 diabetes, a condition which is rising globally. For example, in the UK, 3.2 million people have type 2 diabetes, which is expected to rise to five million people by 2025. The condition is placing a huge financial burden on the NHS, with diabetes costs expected to increase from the current level of £27.3bn to £39.8bn by 2035–2036[4]
.

NICE currently recommends the use of the drug metformin in people who are unable to undertake lifestyle interventions

NHS England introduced the NHS Diabetes Prevention Programme in 2015[5]
, which offers a structured education and lifestyle programme to help people change their health behaviours. NICE also currently recommends the use of the drug metformin in people who are unable to undertake lifestyle interventions[2]
. This includes people who have tried lifestyle interventions and have not been successful or people who are unable to partake in lifestyle interventions such as people with disabilities or physical health conditions (such as those with active arthritis). These policies assume a linear progression from prediabetes to type 2 diabetes and that early identification of the former will allow lifestyle interventions or metformin to reduce the incidence of the latter. This is not the case.

The policies are based on evidence from randomised control trials and observation studies. Seminal studies such as the US Diabetes prevention programme[6]
showed that, in a trial setting, through intensive lifestyle interventions and metformin, the onset of diabetes could be delayed. However, translational studies using less intense interventions, which are more applicable to real-world settings, have not shown a reduction in diabetes risk in their population[7]
,[8]
. Crucially, the tests used to identify trial populations are different from those used in general practice.

Challenges with identifying prediabetes

Currently, there are three different blood tests available that can identify if someone has or is at risk of developing diabetes. The first is a fasting plasma glucose (FPG), which is performed in the morning when the patient is fasting. If this glucose level is elevated but not in the diabetic range, the result is termed impaired fasting glucose (IFG) and is caused by excess hepatic glucose production. After this test is performed the patient ingests a sugary drink (most often Lucozade) and a further blood test is taken two hours later.

The second blood test is the two-hour glucose tolerance test and reflects the degree of insulin resistance in the individual. If this test is abnormal the patient is said to have impaired glucose tolerance (IGT). These two tests can be performed independently of each other but, when performed together, the combination is called the oral glucose tolerance test. There are several disadvantages to these tests, including the inconvenience of fasting, the time taken to perform, and the patient’s potential dislike of sugary drinks. The tests are also subject to daily variance and need to be repeated if an abnormal result is returned.

The term ‘prediabetes’ or ‘non-diabetic hyperglycaemia’ does not mean that the patient will definitely go on to develop diabetes

The third test is the glycated haemoglobin (HbA1c), which looks at how high the blood glucose has been over the past six to eight weeks. This test is more convenient because it requires no fasting and can be done at any time of day. However, it has been shown to be inaccurate in the presence of haemoglobinopathies (such as sickle-cell disease or thalassaemia), and if the patient has a low haemoglobin. The term ‘prediabetes’ or ‘non-diabetic hyperglycaemia’ is an arbitrary category which means the patient has one of these abnormalities. However, such a label does not mean that the patient will definitely go on to develop diabetes, with an average of only 10% progressing to diabetes annually[9]
,[10]
.

The HbA1c is the most convenient test, but people found to have the other abnormalities (IFG and IGT) must be considered. Our systematic review found that the tests are not accurate at identifying each other’s abnormalities[11]
. The reason for this is that each test is looking at different parts of the disease process. In addition, a systematic review looking at progression to diabetes found those at most risk are those with IGT[10]
, with cardiovascular risk factors such as a raised body mass index, high cholesterol or high blood pressure, also influencing an individual’s risk of progression to diabetes. The oral glucose tolerance test is too impractical to act as a screening tool but is still the test of choice for recruiting people into diabetes prevention trials.

There is inconsistency internationally about which test is recommended and which diagnostic thresholds to use

To complicate matters further, there is international inconsistency about which test is recommended and which diagnostic thresholds to use. The American Diabetes Association (ADA)[1]
and NICE [2]
both recommend a low diagnostic threshold for the fasting plasma glucose. The ADA uses a significantly lower threshold for the HbA1c, and the World Health Organization (WHO)[3]
does not currently recommend this test at all. The choice of test and diagnostic thresholds have significant implications for the prevalence of prediabetes and the degree to which the tests overlap. Our systematic review[11]
showed that using the WHO and International Expert Committee[12]
criteria identified a prevalence of prediabetes of 27% in a UK population with limited overlap between the populations identified as abnormal for these tests. When the ADA criteria (lower diagnostic thresholds) were applied to study populations, the degree to which the tests overlapped increased. However, the prevalence of those identified as abnormal increased to 54%. This has a major effect on who is identified as abnormal and the number of people offered lifestyle interventions or metformin.

Another important consideration is the ethnicity and underlying risk factors within the population. An analysis by Yudkin and Montori[13]
showed that, in Chinese populations, half the population were identified as prediabetic by the ADA criteria and that some groups may have naturally higher glycated haemoglobins such as people of African heritage. These test limitations are currently not taken account of in current UK diabetes prevention policies. For example, the economic assessment of this policy uses abnormal HbA1c alone as entry criteria to the programme[14]
.

Other complications with diagnosing prediabetes

A further group of patients worthy of discussion are those with a past medical history of gestational diabetes. Gestational diabetes is a diagnosis given to women who develop diabetes during their pregnancy. This often resolves after pregnancy but women can continue to be diabetic or develop one of the intermediate diabetic states described previously.

Women who revert to normal glucose states following pregnancy have the highest progression to diabetes of all at-risk groups

In these women, the oral glucose tolerance test must be used because the HbA1c is not accurate during, or up to three months after completion of the pregnancy. Women who revert to normal glucose states following pregnancy have the highest progression to diabetes of all at-risk groups, with 70% progressing to diabetes within 10 years of the first gestational diabetes pregnancy[15]
. Children of women who have gestational diabetes have a higher risk of developing diabetes and childhood obesity, resulting both from environmental and genetic influences[16]
. However, despite this evidence, a strategy for reducing diabetes in this group does not currently exist. Lifestyle intervention trials have been ineffective at reducing diabetes progression in this group[11]
.

Future focus

Given the inconsistencies involved in identifying those at risk of diabetes, the limited effectiveness of interventions in real-world settings and the exclusion of important groups such as those with a history of gestational diabetes, we have to ask whether the process of testing, diagnosing and intervening is doing more harm than good. I do not believe that we will ever find the perfect method of identifying those who are at most risk. The ‘prediabetes’ label may cause significant personal harm causing undue stress, anxiety and raised insurance premiums for some people who may never go on to develop diabetes. This label brackets the problem of diabetes development into the biomedical model of health, reducing the importance of social, political and economic influences on diabetes development. It continues the perception that the problem is due to abnormalities within the individual without considering wider community influences such as deprivation, local space and environment, food advertising and affordability of healthy food options.

Moving away from labelling patients

As health professionals, we need to balance the current individualist glucocentric approach of diabetes prevention with wider community and population interventions. Pharmacists have a vital role to play in promoting health and wellbeing to people who use their services, both through their interactions and the products sold in pharmacies. They are also an important point of contact and source of information and reassurance for patients who have been diagnosed with prediabetes and may be anxious about the diagnosis.

Encourage a shift in the pharmacist identity from a biomedical role to a public health role

Greenhalgh et al
[17]
identified a number of ways pharmacists can be supported to deliver such health promotion strategies. The first is to encourage a shift in the pharmacist identity from a biomedical role to a public health role throughout undergraduate training and the support of postgraduate professional bodies. The second is to offer training courses to increase professionals’ capability and confidence in performing this role. The third is to offer motivational incentives for this role through peer support and strategic investment. The fourth is to improve local links between pharmacists and primary care with formalised referral pathways. Through these strategies pharmacists can incorporate a public health-oriented approach to promote a healthy community and support individuals trying to undertake lifestyle change. Pharmacists provide an important advocacy role for their community and can play an important part in public health decision making and strategies in the pursuit of producing a healthy society.

Eleanor Barry is a general practitioner and National Institute for Health Research (NIHR) In-Practice Fellow at the Nuffield Department of Primary Care Health Sciences at the University of Oxford.

Disclosure: Dr Barry is supported by the NIHR to continue her research training, undertaking an MSc in public health.

References

[1] American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010;33(suppl 1):S62–69. doi: 10.2337/dc10-S062

[2] National Institute for Health and Care Excellence. Type 2 diabetes: prevention in people at high risk. NICE Guideline PH 38. 2012. Available at: https://www.nice.org.uk/guidance/ph38 (accessed June 2017)

[3] World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. WHO, 2006. Available at: http://www.who.int/diabetes/publications/Definition%20and%20diagnosis%20of%20diabetes_new.pdf (accessed June 2017)

[4] Diabetes UK. Diabetes: Facts and Stats. 2015. Available at: https://www.diabetes.org.uk/Professionals/Position-statements-reports/Statistics/ (accessed June 2017)

[5] NHS England. NHS Diabetes Prevention Programme (NHS DPP). In: England N, editor. London 2015. Available at: https://www.england.nhs.uk/ourwork/qual-clin-lead/diabetes-prevention/ (accessed June 2017)

[6] Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol 2015;3:866–875. doi: 10.1016/S2213-8587(15)00291-0

[7] Davies MJ, Gray LJ, Troughton J  et al. A community based primary prevention programme for type 2 diabetes integrating identification and lifestyle intervention for prevention: the Let’s Prevent Diabetes cluster randomised controlled trial. Prev Med 2016;84:48–56. doi: 10.1016/j.ypmed.2015.12.012

[8] Wareham NJ. Mind the gap: efficacy versus effectiveness of lifestyle interventions to prevent diabetes. Lancet Diabetes Endocrinol 2015;3(3):160–161. doi: 10.1016/S2213-8587(15)70015-X

[9] Zhang X, Gregg E, Williamson D et al. A1C level and future risk of diabetes: a systematic review. Diabetes Care 2010;33:1665–73. doi: 10.2337/dc09-1939

[10] Morris D, Khunti K, Achana F et al. Progression rates from HbA1c 6.0-6.4% and other prediabetes definitions to type 2 diabetes: a meta-analysis. Diabetologia 2013;56:1489-1493. doi: 10.1007/s00125-013-2902-4

[11] Barry E, Roberts S, Oke J et al. Efficacy and effectiveness of screen and treat policies in prevention of type 2 diabetes: systematic review and meta-analysis of screening tests and interventions. BMJ 2017;356:i6538. doi:10.1136/bmj.i6538

[12] International Expert Committee. International expert committee report on the role of the A1c assay in the diagnosis of diabetes. Diabetes Care 2009;32(7):1327–1334. doi: 10.2337/dc09-9033

[13] Yudkin J & Montori V. The epidemic of pre-diabetes: the medicine and the politics. BMJ 2014;349:g4485. doi: 10.1136/bmj.g4485

[14] Public Health England. Healthier you: NHS diabetes prevention programme. Assessing the potential return on investment of the proposed healthier you: NHS Diabetes Prevention Programme in different population subgroups. London 2016. Available at: http://www.healthcheck.nhs.uk/commissioners_and_providers/delivery/healthier_you_nhs_diabetes_prevention_programme/ (accessed June 2017)

[15] Bellamy L, Casas J, Hingorani A et al. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 2009;373):1773–1779. doi: 10.1016/S0140-6736(09)60731-5

[16] Greenhalgh T, Clinch M, Afsar N et al. Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach. BMC Med 2015;13(120). doi: 10.1186/s12916-015-0360-1

[17] Greenhalgh T, Macfarlane F, Steed L et al. What works for whom in pharmacist-led smoking cessation support: realist review. BMC Med 2016;14(1):209. doi: 10.1186/s12916-016-0749-5

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Citation
Clinical Pharmacist, CP, June 2017, Vol 9, No 6;9(6):DOI:10.1211/PJ.2017.20202674