See also: Screening for Diabetes, Insulin Resistance, Managing Impaired Glucose Tolerance in Primary Care, Gestational Diabetes, Diabetes Education and Self-management Programmes.

The type 2 diabetes epidemic

• It is thought that diabetes affects 1 in 20 adults across the world and projections estimate that there will be over 300 million cases worldwide by 2025.¹
• Although effective treatment of diabetes can reduce the incidence of its complications, type 2 diabetes is more often than not an asymptomatic condition and it is thought that many people with type 2 diabetes may have had the condition for 9–12 years before diagnosis.²
• This means that many of its sufferers have macrovascular and microvascular complications by the time their condition is diagnosed.³
• Although there is no population-based evidence as yet that confirms that earlier diagnosis and treatment of undiagnosed type 2 diabetes will improve outcomes, it seems likely that such a strategy will be useful as the prevalence of type 2 diabetes rises in the general population.
• See the separate article Screening for Diabetes (click here) for details of how such screening may be carried out and the interpretation of fasting plasma glucose results in this scenario.

The metabolic syndrome and 'pre-diabetes'

• Research examining the role of screening for type 2 diabetes has shown that there is a significant minority of patients in the at-risk group who have impaired fasting glucose.
• One study looking at an older British, predominantly white, socially representative cohort of patients enrolled in heart disease studies, showed 1 in 5 patients had impaired fasting plasma glucose.⁴
• This significant cohort is considered to be suffering from 'pre-diabetes' and the features of the metabolic syndrome (an overlapping constellation of risk factors comprising obesity, hypertension, insulin resistance and dyslipidaemia), and therefore at a significantly increased risk of developing type 2 diabetes and its vascular complications.
• The degree of overlap between the populations with impaired fasting glucose and impaired glucose tolerance, as demonstrated by glucose tolerance testing, is not clear and research findings in one population are not necessarily transferable to the other.
• There is some preliminary evidence that identifying such patients and addressing their vascular risk factors, through lifestyle changes or through manipulation of the renin-angiotensin-aldosterone system (RAAS) or the use of thiazolidinediones, can improve outcomes and even reduce the incidence of progression to type 2 diabetes in this group.^5,6,7

Identifying patients at risk of 'pre-diabetes' in primary care

• As yet there are no agreed protocols on selection of the best population for screening for type 2 diabetes and/or impaired glucose tolerance. Screening on the basis of age alone has been shown to have a low yield.⁸
• Most studies use all or some of the following criteria to identify the population that may benefit from the detection of frank type 2 diabetes or 'pre-diabetes':
  • Age >45–50
  • Body mass index (BMI) >27–30
  • Membership of a high-risk ethnic group for type 2 diabetes, e.g. UK-based African-Caribbean- or Asian-origin populations⁹
  • Family history of type 2 diabetes¹⁰
  • High waist circumference¹⁰
  • Sedentary lifestyle¹⁰

Other criteria might include those with cardiovascular disease, a history of gestational diabetes, obese women with polycystic ovary syndrome and previous evidence of impaired glucose tolerance.

However, the more complex the criteria for selecting the at-risk population become, the more difficult it will be to find cases, so a balance must be struck between ease of information retrieval and more honed indicators of possible 'pre-diabetes' or type 2 diabetes.

Screening investigations and their interpretation

• Again, there are no definitely agreed protocols for what tests to do and how to interpret them in the population at large.
• Fasting venous plasma glucose measurement is the usual test used in the research done in this area. It is possible that measurement of capillary glucose may be sufficient but this has not been validated by large studies as yet.
• Glucose tolerance testing can also be used, particularly in cases where there is doubt as to the diagnosis.
• A large, validated UK-based study used the interpretations below to classify patients into the relevant groups for possible intervention:¹⁰
  • Fasting plasma glucose of <6.1 mmol/l: unlikely to have impaired glucose metabolism; should be re-enlisted for further screening at a later date (probably in a further 3 years or so).
  • Fasting plasma glucose of 6.1–6.9 defined as having impaired fasting glycaemia (needs an oral glucose tolerance test to clarify whether they have diabetes or impaired glucose tolerance).
  • Fasting plasma glucose of >7 mmol/l or random plasma glucose of >11.1 mmol/l is diagnostic of diabetes.¹¹

What strategies work in preventing progression to diabetes in those with 'pre-diabetes'?

Lifestyle interventions

• There is good evidence to show that people who receive interventions to help them alter their lifestyle, in a research setting, have a significant reduction in their risk of developing type 2 diabetes compared to those who do not receive such intervention.
• The Diabetes Prevention Program Research Group study found that lifestyle interventions delivered over a period of almost 3 years reduced the incidence of diabetes in the intervention group by 58%;¹² a smaller Finnish study showed very similar results.¹³
• However such interventions were extremely labour-intensive. Repeated one-to-one sessions delivered by appropriately trained case managers (up to 16 sessions in one of the studies) were needed to bring about targets in weight reduction and increased exercise.
• It is difficult, but not impossible, to imagine a sufficient level of funding, and motivation by healthcare workers and patients, to bring about such improvements in the general population at risk of diabetes.
• The fact that the subjects were prepared to take part in a trial involving lifestyle intervention suggests that their motivation and responsiveness to this mode of health modification is higher than that of the general population.
• The prevalence of smoking in the trial population was 7% - significantly lower than the UK national prevalence of 24%.¹⁴
• It would appear unlikely, currently, that the same gain from lifestyle intervention would be seen in a real-world scenario.¹⁵

Medication

• The Diabetes Prevention Program Research Group study found that the use of metformin reduced the incidence of progression to diabetes by 31%.¹²
• In obese people, orlistat has been shown to reduce the risk of diabetes, when used as an adjunct to lifestyle modification, by 37% compared to placebo.¹⁶
• The recently published Diabetes Reduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial examined the role of these drugs in influencing the risk of progression to diabetes in those with impaired fasting glucose, impaired glucose tolerance, or both. Of those taking rosiglitazone, 11.6% became diabetic, compared to 26% of those receiving placebo:¹⁷
  • This result requires careful interpretation as using criteria other than impaired fasting glucose may invalidate the findings in a UK population, where this is the predominant method of picking up cases of 'pre-diabetes'.¹⁸
  • There seemed to be a significant increase in the rate of heart failure in the rosiglitazone group and the rate of all cardiovascular events was higher in the intervention group.¹⁸ This has resulted in the withdrawal of rosiglitazone in the UK.¹⁹
  • There was no evidence of any beneficial effect of taking ramipril in terms of progression from 'pre-diabetes' to diabetes.²⁰

So what does this all mean in the real world?

It is difficult to be certain of the implications of recent research findings in terms of strategies to prevent progression to type 2 diabetes in an at-risk population in primary care in the real world, rather than in a research population. The following observations are opinion based on a review of the literature, as above, but are not definitive and are prone to change as more detailed studies are carried out into the best ways to prevent type 2 diabetes:

• By far the best way to reduce the incidence and therefore the burden of diabetes in the population at large in the future is for there to be a sea-change in attitudes and behaviours among the general population with regard to physical activity and diet. This is going to be hard to achieve and will require real political will and a positive influence from the healthcare professions at the political, community and personal levels.
• Screening for type 2 diabetes appears to be a useful strategy to detect undiagnosed cases in primary care, allowing early offering of appropriate therapy, but as yet there is no definitive evidence of benefit in adopting such a strategy. The separate article can be seen by clicking here.
• It is possible to detect cases of 'pre-diabetes' by screening an at-risk population in primary care but, as yet, there are no validated and agreed criteria to choose the population, nor to judge the results of screening, and certainly no confirmed best strategy with which to approach the prevention of diabetes in those detected by screening.
• It is certain that lifestyle intervention with regard to diet, exercise and weight reduction is an effective and safe way to reduce the risk of progression to type 2 diabetes in those found to have impaired fasting glucose.²¹
• Reproducing the degree of effectiveness of lifestyle interventions from research trials, in a real-world population, is likely to be difficult and at least a little disappointing, but this is not necessarily a reason not to proceed with this approach and find those strategies that work best.
• The jury is still out on whether the use of thiazolidinedione medication is an effective and safe way to prevent type 2 diabetes. Initial results are mildly encouraging but the long-term efficacy and safety has yet to be established.
• There is no convincing evidence that ACE inhibitors have any role to play in prevention of type 2 diabetes in those at risk of developing it.
• A combination of lifestyle intervention and the use of metformin, particularly in those that are significantly obese, appears to be a safe, effective and relatively cheap way to achieve significant rates of diabetes prevention in populations of 'pre-diabetics'.¹⁵
• Great care should be taken not to medicalise what is essentially a personal lifestyle and societal issue.
• Should we spend our money on medications to prevent type 2 diabetes, rather than on lifestyle measures and public health strategies? What is the best way to reduce the burden of this largely preventable chronic disease in our modern, abundant, sedentary societies?¹⁸

Document references

1. King H, Aubert RE, Herman WH; Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414-31. [abstract]
2. Position Statement: Early identification of people with Type 2 diabetes, Diabetes UK, Jun 2006
3. Harris MI, Eastman RC; Early detection of undiagnosed diabetes mellitus: a US perspective. Diabetes Metab Res Rev. 2000 Jul-Aug;16(4):230-6. [abstract]
4. Thomas MC, Walker MK, Emberson JR, et al; Prevalence of undiagnosed Type 2 diabetes and impaired fasting glucose in older British men and women.; Diabet Med. 2005 Jun;22(6):789-93. [abstract]
5. Leiter LA; Can thiazolidinediones delay disease progression in type 2 diabetes? Curr Med Res Opin. 2006 Jun;22(6):1193-201. [abstract]
6. Deedwania PC, Schmieder R; Angiotensin receptor blockers: Cardiovascular protection in the metabolic syndrome. J Renin Angiotensin Aldosterone Syst. 2006 Jun;7 Suppl 1:S12-8. [abstract]
7. Vijayaraghavan K, Deedwania PC; The renin angiotensin system as a therapeutic target to prevent diabetes and its complications. Cardiol Clin. 2005 May;23(2):165-83. [abstract]
8. Lawrence JM, Bennett P, Young A, et al; Screening for diabetes in general practice: cross sectional population study. BMJ. 2001 Sep 8;323(7312):548-51. [abstract]
9. Ramachandran A, Snehalatha C, Vijay V, et al; Derivation and validation of diabetes risk score for urban Asian Indians. Diabetes Res Clin Pract. 2005 Oct;70(1):63-70. Epub 2005 Apr 15. [abstract]
10. Greaves CJ, Stead JW, Hattersley AT, et al; A simple pragmatic system for detecting new cases of type 2 diabetes and impaired fasting glycaemia in primary care. Fam Pract. 2004 Feb;21(1):57-62. [abstract]
11. Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycaemia, World Health Organization/International Diabetes Federation, 2006
12. Knowler WC, Barrett-Connor E, Fowler SE, et al; Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403. [abstract]
13. Tuomilehto J, Lindstrom J, Eriksson JG, et al; Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343-50. [abstract]
14. National Statistics Online; Prevalence of cigarette smoking in Great Britain
15. Ashcroft JS; Prevention of diabetes: lifestyle and metformin are the way forward. BMJ. 2006 Oct 28;333(7574):918-9.
16. Torgerson JS, Hauptman J, Boldrin MN, et al; XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004 Jan;27(1):155-61. [abstract]
17. Gerstein HC, Yusuf S, Bosch J, et al; Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006 Sep 23;368(9541):1096-105. [abstract]
18. Heneghan C, Thompson M, Perera R; Prevention of diabetes. BMJ. 2006 Oct 14;333(7572):764-5.
19. Rosiglitazone (Avandia, Avandamet): Recommended withdrawal from clinical use, MHRA (Safety Information)
20. Bosch J, Yusuf S, Gerstein HC, et al; Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006 Oct 12;355(15):1551-62. Epub 2006 Sep 15. [abstract]
21. Pinkney J; Prevention and cure of type 2 diabetes. BMJ. 2002 Aug 3;325(7358):232-3.

Internet and further reading

• Type 2 diabetes risk assessment form, Finnish Diabetes Association (2001); Test designed by Professor Jaakko Tuomilehto, Department of Public Health, University of Helsinki, and Jaana Lindström, MFS, National Public Health Institute, Finland.
• Leiter LA, Lewanczuk RZ; Of the renin-angiotensin system and reactive oxygen species Type 2 diabetes and angiotensin II inhibition. Am J Hypertens. 2005 Jan;18(1):121-8. [abstract]
• Hu G, Rico-Sanz J, Lakka TA, et al; Exercise, genetics and prevention of type 2 diabetes. Essays Biochem. 2006;42:177-92. [abstract]
• Case J, Willoughby D, Haley-Zitlin V, et al; Preventing type 2 diabetes after gestational diabetes. Diabetes Educ. 2006 Nov-Dec;32(6):877-86. [abstract]
• Diabetes risk in Asians. Asians are more likely to get diabetes. An expert explains simple dietary changes that can reduce your risk, and makes healthy versions of rice pudding and samosas. A short video from NHS Choices. (December 2008)

Acknowledgements