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Meta-Analysis of Randomized Controlled Trials Downloaded from pmj.bmj.com on 8 September 2009 Preventing type 2 diabetes: can we make the evidence work? T Yates, M Davies and K Khunti Postgrad. Med. J. 2009;85;475-480 doi:10.1136/pgmj.2008.076166 Updated information and services can be found at: http://pmj.bmj.com/cgi/content/full/85/1007/475 These include: References This article cites 54 articles, 24 of which can be accessed free at: http://pmj.bmj.com/cgi/content/full/85/1007/475#BIBL Rapid responses You can respond to this article at: http://pmj.bmj.com/cgi/eletter-submit/85/1007/475 Email alerting Receive free email alerts when new articles cite this article - sign up in the box at service the top right corner of the article Notes To order reprints of this article go to: http://journals.bmj.com/cgi/reprintform To subscribe to Postgraduate Medical Journal go to: http://journals.bmj.com/subscriptions/ Downloaded from pmj.bmj.com on 8 September 2009 Review Preventing type 2 diabetes: can we make the evidence work? T Yates,1 M Davies,1 K Khunti2 1 Department of Cardiovascular ABSTRACT 15% of adults have prediabetes based on WHO Sciences, University of 810 2 Type 2 diabetes is associated with many serious criteria, of which an estimated 5–12% develop Leicester, UK; Department of type 2 diabetes per year.810 The risk of cardiovas- Health Sciences, University of comorbidities and is one of the leading causes of mortality Leicester, UK globally. Type 2 diabetes is preceded by a condition called cular disease is also significantly elevated with prediabetes, which is characterised by elevated glucose prediabetes.11 Given these factors, individuals with Correspondence to: concentrations resulting from peripheral and/or hepatic prediabetes will form a significant proportion of Dr T Yates, Diabetes Research the health care burden associated with diabetes in Unit, Level 1 Victoria Building, insulin resistance. Individuals with prediabetes have been Leicester Royal Infirmary, the traditional target of diabetes prevention programmes; the future and therefore have been the target of a Leicester LE1 5WW, UK; ty20@ these have consistently shown that lifestyle modification number of diabetes prevention initiatives. le.ac.uk can significantly reduce the risk of developing type 2 The aims of this article are: to give an overview diabetes. This has led to the implementation of diabetes of the evidence from diabetes prevention trials in Received 23 October 2008 high risk populations; to review the clinical utility Accepted 11 May 2009 prevention initiatives in several countries. However, a number of key areas still need to be addressed. For of different strategies for identifying at-risk indivi- example, important questions remain regarding how best duals; and to investigate whether tested diabetes to identify at-risk individuals and whether the findings prevention strategies are suitable for implementa- from resource intensive research projects can be tion in a primary health care setting. replicated using pragmatic lifestyle interventions tailored to the resources and infrastructure available to usual STRATEGIES FOR PREVENTING TYPE 2 DIABETES health care practice. This article highlights findings from Lifestyle diabetes prevention programmes and discusses key Randomised controlled trials have consistently issues involved in translating research into practice. shown that lifestyle interventions can be successful at reducing the risk of progressing to type 2 diabetes by 40–60% in those with IGT.12 For Type 2 diabetes mellitus is a chronic and debilitat- example, the Finnish Diabetes Prevention Study ing disease characterised by an inability to ade- (DPS) found that the risk of type 2 diabetes was quately regulate blood glucose concentrations. In reduced by 58% in those given lifestyle counselling the short term the symptoms of type 2 diabetes are compared to control conditions over a 3 year associated with a reduced quality of life, while in period.13 Identical findings were also seen in the the longer term the disease may lead to serious USA in the Diabetes Prevention Program (DPP).14 complications such as cardiovascular disease, blind- These results have also been replicated in India,15 1 ness, renal failure and amputation. The life Japan16 and China.17 The aim of these interventions expectancy of individuals with type 2 diabetes was to promote moderate to vigorous intensity may be shortened by as much as 15 years, with up physical activity, generally 150 min per week, and 2 to 75% dying of cardiovascular disease. a healthy diet aimed at weight maintenance for The prevalence of type 2 diabetes mellitus has normal weight individuals or weight loss for risen so sharply over the past half century that it is overweight or obese individuals. For example, the 34 now commonly referred to as an epidemic, and it Finnish DPS had five intervention goals: a reduc- is currently estimated to be the fifth leading cause tion in body weight of 5% or more; ,30% of 5 of mortality globally. In the UK, approximately energy intake derived from fat; ,10% of energy 5% of the total National Health Service resources intake derived from saturated fat; at least 15 g of and up to 10% of hospital inpatient resources are fibre per 1000 kcal; and at least 30 min of moderate devoted to the care and treatment of type 2 intensity physical activity per day.13 Of note, there diabetes6; these figures are set to rise in the future was not a single case of type 2 diabetes over the and will represent a serious clinical and financial course of the study in those who achieved at least challenge to the UK’s health system.7 four of these goals.13 The same study also reported Type 2 diabetes is at one end of a continuous that, compared to those in lowest tertile of leisure glucose control spectrum with normal glucose time physical activity change, those in the highest control at the other. In between there exists a tertile had around a 70% reduction in the relative condition called prediabetes or intermediate hyper- risk of developing type 2 diabetes18 Similarly, those glycaemia, defined as impaired glucose tolerance in the US DPP who achieved their weight, dietary (IGT) and/or impaired fasting glucose (IFG),89 fat and exercise goals had around a 90% reduction where blood glucose concentrations are elevated in the relative risk of developing type 2 diabetes above the normal range but do not satisfy the compared to those who achieved none of these criteria for type 2 diabetes (see table 1 for a goals.19 The large decreases in the risk of type 2 definition of the current World Health diabetes seen with lifestyle change are unsurprising Organization criteria). In most countries around given that the rising prevalence of type 2 diabetes is Postgrad Med J 2009;85:475–480. doi:10.1136/pgmj.2008.076166 475 Downloaded from pmj.bmj.com on 8 September 2009 Review Table 1 World Health Organization criteria for impaired glucose in those with both IGT and IFG and one other risk factor tolerance and impaired fasting glucose (table 2).29 Metformin was chosen because it has a proven 2 h post challenge preventive efficacy, it is relatively cheap, and is not associated Fasting glucose range glucose range* with serious long term side effects. However, this approach remains controversial for several reasons. Firstly, few studies Impaired glucose ,7 mmol/l >7.8 mmol/l and tolerance ,11.1 mmol/l have assessed the impact of metformin and lifestyle modifica- Impaired fasting >6.1 mmol/l and (6.9 mmol/l ,7.8 mmol/l tion in combination; the only study to do so, the Indian glucose Diabetes Prevention Program, found that there was no additive *Venous plasma glucose after ingesting 75 g of glucose solution. benefit of combining metformin with a lifestyle modification programme in those with IGT.15 Secondly, given the causal factors of type 2 diabetes, lifestyle modification programmes attributable to so called ‘‘obesogenic’’ modern environments should be the primary focus of diabetes prevention initiatives. where energy dense foods are plentiful and the link between Importantly, lifestyle change, such as increased physical physical activity and food procurement has been broken; the activity, is also associated with multiple and wide ranging timescale associated with the rising prevalence of type 2 health benefits that target the known comorbidities that diabetes means genetic change cannot be a causal factor. accompany type 2 diabetes.30 While logistical and feasibility Therefore, lifestyle change directly targets the root cause of issues remain in implementing lifestyle programmes in a type 2 diabetes. primary health care or community setting, it is the responsi- Importantly, successful lifestyle change programmes have bility of funding bodies and research organisations to carry out also been shown to have lasting benefits. For example, DPS the necessary research to address this issue. However, we recently reported that the intervention effect was sustained at acknowledge that pharmacotherapy may have a role to play 7 years20 and the China Da Qing prevention study found a when lifestyle modification programmes have been tried and sustained reduction in the incidence of type 2 diabetes after found to fail. 20 years.21 Both these results were achieved despite the active lifestyle intervention discontinuing after the initial study IDENTIFYING THOSE AT RISK period. Therefore, it would appear that once individuals are Utility of the oral glucose tolerance test enabled to successfully self regulate their behaviour, change can be sustained long after behavioural counselling has ceased. In order for diabetes prevention strategies to be implemented on a regional or national level it is essential that systematic strategies for identifying those at risk of developing type 2 Pharmacotherapy diabetes are also implemented. Successful diabetes prevention Several oral hypoglycaemic agents have been shown to reduce studies have tended to include participants on the basis of IGT, the risk of developing type 2 diabetes in double blind which is diagnosed through the oral glucose tolerance test randomised controlled trials.
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