Editorials

Targeting people with pre-diabetes

Lifestyle interventions should also be aimed at people with pre-diabetes

Three major randomised controlled trials, conducted in diverse countries, settings, and populations, confirm that effective lifestyle intervention can prevent or delay the progression to type 2 diabetes in groups at high risk, such as overweight people with impaired glucose tolerance (glucose concentration 7.8-11.1 mmol/l, two hours after a 75 g loading).^1-3 In the largest of these trials, the diabetes prevention programme in the United States, a lifestyle modification programme was delivered with the goals of at least a 7% weight loss and at least 150 minutes of physical activity per week.⁴ At 24 weeks, 50% of the participants in the lifestyle intervention group had achieved the weight loss goal and 74% had achieved the activity goal. In this trial, lifestyle intervention reduced the incidence of diabetes by 58%, and one case of diabetes was prevented for every 6.9 people treated for three years.³

In response to this impressive evidence, the American Diabetes Association's position statement on prevention of diabetes has recommended screening to detect people with impaired glucose tolerance or impaired fasting glucose (fasting glucose concentration 6.1-7.0 mmol/l) during healthcare office visits by people aged over 45particularly those with a body mass index of 25 or more.⁴ People found to have impaired glucose tolerance or impaired fasting glucose (collectively referred to as pre-diabetes) will be given counselling on weight loss as well as instruction on increasing their physical activity.⁴

Type 2 diabetes has long been linked with behavioural, environmental, and societal factors such as overweight, physical inactivity, sedentary behaviour, and unhealthy dietary habits.⁵ It may be intuitive and tempting to argue that programmes designed to prevent diabetes should be aimed at the underlying determinants of lifestyles in society and therefore should be delivered to the population at large.⁶ There are, however, several reasons, based on epidemiology, pathophysiology, and patterns of human behaviour, why we should focus our energy and effort on prevention programmes for people at high risk for diabetes, such as those with pre-diabetes.

Firstly, the relation between glycaemia and incidence of diabetes is non-linear, with the risk threshold coinciding with the onset of pre-diabetes. In the Hoorn study, risk for conversion to diabetes during 6.5 years of follow up was more than 10 times higher in people with impaired glucose tolerance (57.9/1000 person years) or impaired fasting glucose (51.4/1000 person years) than in people with normoglycaemia (7/1000 person years).⁷

Secondly, although 8% of people in the Hoorn study had impaired glucose tolerance, 40% of cases of incident diabetes were attributable to impaired glucose tolerance. Similarly, 10% had impaired fasting glucose, but 42% of cases of diabetes were attributable to impaired fasting glucose. The risk of conversion to diabetes is equivalent for impaired glucose tolerance and impaired fasting glucose, but these two abnormalities overlap only 20-25%.⁷ This is why the American Diabetes Association has defined pre-diabetes as either impaired glucose tolerance or impaired fasting glucose.⁴ Approximately 17 million people in the United Statesabout as many as have diabeteshave pre-diabetes.

Thirdly, clinical trials have shown evidence of benefit (that is, prevention or delay of diabetes) only for people with pre-diabetes.^1-3

Fourthly, all people who develop diabetes go through pre-diabetes, although the length of this phase may vary.⁵ Effectively delivering lifestyle intervention to people with pre-diabetes will therefore ensure that most, if not all, future cases of diabetes are targeted.

Fifthly, patterns of human behaviour also support focusing on people with pre-diabetes. The "health belief model" suggests that for people to comply with participatory preventive interventions, they will need to perceive both risk and potential benefit.⁸ People with pre-diabetes are at very high risk for diabetes,⁷ and evidence points to high potential benefit from lifestyle interventions.^1-3 According to the theory of "diffusion of innovations," a new intervention is best applied to a small proportion of the population that is likely to adopt it; then, societal forces will facilitate spreading such interventions to others in a sequential manner.⁹ Consistent with these behavioural theories, focusing efforts on people with pre-diabetes, who comprise over 20% of overweight people over 45 and who are most likely to adopt a challenging intervention, is a strategically sound approach to preventing diabetes.

The compelling evidence for success in preventing or postponing type 2 diabetes should be viewed as a catalyst for promoting lifestyle modifications across society. Undoubtedly, population based public health efforts will be needed to encourage and support healthy lifestyles. Such societal approaches are complementary to, and not at odds with, a clinical approach of targeting and treating people who have pre-diabetes.⁶ For a primary care practitioner, focusing on detecting people with pre-diabetes and delivering effective lifestyle intervention to them is an immediate and difficult challenge. Further assessment will be needed to determine whether detection will require opportunistic screening with fasting glucose alone, with an oral glucose tolerance test, or with simpler and cheaper methods (such as a multivariate diabetes risk score).¹⁰ Similarly, lifestyle interventions can be delivered in many ways: individual counselling, group counselling, and workplace based programmes. Regardless of all these factors, prevention of diabetes through lifestyle modification among people with pre-diabetes has arrived, and this new challenge needs to be met. Awareness of pre-diabetes, which is low among primary care doctors,¹¹ needs to be raised, and guidelines for its management are urgently needed.

K M Venkat Narayan, adjunct professor. 

(kav4{at}cdc.gov)

Giussepina Imperatore, medical epidemiologist. 
Stephanie M Benjamin, epidemiologist. 
Michael M Engelgau, chief, epidemiology and statistics branch. 

Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Mailstop K-10, 4770 Buford Highway NE, Atlanta, GA 30341, USA