Type-2 diabetes is a growing health problem, with prevalence of the disease set to rise dramatically in westernised societies. Patients with diabetes have a life expectancy that can be shortened by as much as 15 years, with up to 75 per cent dying of macrovascular complications.
In England there are currently around 1.3 million patients diagnosed with diabetes and around 5 per cent of total NHS resources and up to
10 per cent of hospital inpatient resources are used for the care of patients with diabetes. Intervening to delay or even prevent type-2 diabetes therefore has great potential for improving the health of our population, as well as for reducing the burden of healthcare costs.
An increase in obesity and a decrease in physical activity are strongly linked with the increase in the prevalence and incidence of type-2 diabetes.
A number of trials have therefore been carried out to assess the potential benefits of intervening in high-risk patients, such as those who already have impaired glucose tolerance, to prevent type-2 diabetes. Interventions have been wide ranging and include pharmacological treatments such as anti-diabetic agents and anti-obesity drugs.
In addition, intensive lifestyle interventions have looked at improving the diet and exercise regimens of patients at risk through counselling, dietary advice and exercise programmes.
In a recent study by our research group at the University of Leicester, the evidence for diabetes prevention was reviewed by carrying out a systematic review and meta-analysis of all relevant intervention trials.
We found intensive lifestyle interventions to be at least as effective as taking prescription drugs. Combining all the trial results we found that, on average, intensive lifestyle interventions compared with standard advice helped to significantly reduce the risk of developing type-2 diabetes by around half.
In comparison, oral anti-diabetic agents compared with placebo reduced the risk of diabetes on average by about one third.
One of the pharmacological studies, the DPP trial, reported progression to type-2 diabetes after withdrawal from metformin. Results showed the reduction in progression to type-2 diabetes was not actually sustained after discontinuation of the drug.
Because the use of anti-diabetic agents would involve long-term medication, the assessment of compliance with and side-effects of these agents are important when considering their feasibility.
Our review of intervention trials found that many reported adverse gastrointestinal effects, which were attributed to the anti-diabetic agents. As many as 35 per cent of the intervention group were affected, which questions the suitability of such interventions for all patients at risk of type-2 diabetes.
Generally, it would be fair to assume that lifestyle interventions would incur fewer and less serious side-effects than pharmacological interventions, but as with the pharmacological interventions their effect may not be permanent and dietary and exercise advice may need to be reinforced on a regular basis.
The Finnish diabetes prevention study group has recently published a longer-term follow-up and shown that lifestyle interventions result in sustained lifestyle changes and a reduction in diabetes incidence, which remain after the individual lifestyle counselling is stopped.
Although compliance with intensive lifestyle interventions was high in the trials, it is yet to be determined whether compliance and the effectiveness of lifestyle interventions could be maintained in the real world.
While both pharmacological and intensive lifestyle interventions have been shown to be clinically effective in significantly reducing the risk of developing type-2 diabetes in patients with impaired glucose tolerance, a number of issues remain.
Determining the best approach to intervening, be it pharmacological or lifestyle, is dependent not just on their performance in trial settings but on a number of issues that are not yet resolved.
For pharmacological interventions the adverse effects need to be fully understood to enable potential harms and benefits to be assessed. There is also concern over whether a lifestyle problem should be treated with a life-long course of medication.
Compliance is the key to their success of lifestyle interventions, therefore strategies to assist compliance need to be carefully thought through and implemented.
Lifestyle interventions also have additional benefits over anti-diabetic agents in that they may reduce the risk of other diseases where obesity is a risk factor, such as CHD.
Because intervention trials focus on patients at high risk of type-2 diabetes, the overall clinical and cost-effectiveness of a policy of diabetes prevention must consider how different identification and screening strategies would impact on the evaluation of such policies, and further work is required.
Ms Gillies is a medical statistician, Professor Abrams is professor of medical statistics, Dr Lambert is senior lecturer in medical statistics and Dr Khunti is clinical senior lecturer at the Department of Health Sciences, University of Leicester
- Davies M J, Tringham J R, Troughton J, Khunti K K. Prevention of type 2 diabetes mellitus. A review of the evidence and its application in a UK setting. Diabet Med 2004; 21: 403–14.
- Department of Health. National service framework for diabetes: standards. London: DoH, 2001.
- Gillies C L, Abrams K R, Lambert P C et al. Pharmacological and lifestyle interventions to prevent or delay type-2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ 2007; 334: 299.
- Diabetes Prevention Program Research Group. Effects of withdrawal from metformin on the development of diabetes in the diabetes prevention program. Diabetes Care 2003; 26: 977–80.
- Lindstrom J, Ilanne-Parikka P, Peltonen M et al. Sustained reduction in the incidence of type-2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet 2006; 368: 1,673–9.