ADA 2019: PREVIEW Study Results – Prevention of Diabetes Through Lifestyle Intervention and Population Studies Around the World

Diabetes is a global health and economic crisis. The International Diabetes Federation estimates that there are 425 million people currently living with diabetes around the world and that the global direct healthcare costs from diabetes reached $727 billion in 2017.¹ If indirect costs are considered, the global cost rises to $1.31 trillion.² This is projected to rise to $2.2 trillion by 2030.³ The rising incidence of type 2 diabetes (T2D) and its complications is mainly driven by a global increase in the prevalence of obesity.⁴ There is a need for urgent action to prevent the development and progression of T2D.

A number of studies have demonstrated that lifestyle interventions can reduce the risk of T2D. One of the first was the Finnish Diabetes Study, which found that an intensive lifestyle intervention reduced the risk of T2D in middle-aged, overweight people with impaired glucose tolerance.⁵ In 2002, the Diabetes Prevention Program Research Group study showed that lifestyle intervention with the goals of at least a 7% weight loss and at least 150 minutes of moderate intensity exercise per week was more effective than metformin in reducing the incidence of T2D in high-risk individuals.⁶ However, these studies have not determined which diet is most effective for weight loss or prevention of weight re-gain. The low carbohydrate diet, the ketogenic diet, the vegan diet, and the Mediterranean diet have been shown to assist in improving glycaemic control and weight loss.⁷ A diet with high fibre and low glycaemic load has been associated with a reduced risk of gestational diabetes.⁸ A modest increase in protein content and a modest reduction in the glycaemic index (GI) has also been associated with the maintenance of weight loss.⁹ However, patient adherence, acceptability, and long-term manageability are key to the success of any dietary intervention.⁷

The PREVIEW (Prevention of Diabetes Through Lifestyle Intervention and Population Studies in Europe and Around the World) study (NCT01777893) is a large multicentre randomised intervention study in six EU countries (Bulgaria, Denmark, Finland, Spain, Netherlands, UK), Australia and New Zealand. The study aims to define a dietary regime that, in combination with physical activity, can prevent the development of T2D and its complications. The project also comprises observational studies aiming to evaluate the influence of lifestyle factors, social environments and cultural habits. The announcement of the results of the randomised study was one of the hot topics of the 79th Scientific Sessions of the American Diabetes Association (ADA), which was held from 7 to 11 June 2019, in San Francisco, CA.

A total of 2,233 overweight or obese adult participants (aged 25–70 years) were enrolled in the study. Patients were recruited based on body mass index and other components of the Finnish Diabetes Risk Score. Prediabetes was defined by fasting plasma glucose and 2-hour post oral glucose tolerance test (OGTT) scores indicating impaired fasting and/or post OGTT glucose values. All adult participants underwent a low-calorie diet for 8 weeks, with the aim of achieving a weight reduction of at least 8%. Of these, 2,202 (98.6%) successfully lost the weight and proceeded to the next stage. Participants were then randomly assigned to one of four treatment arms, which comprised two different diet interventions (high protein/low-GI [protein intake 25%, carbohydrate 45%, GI ≤ 55] versus moderate protein/moderate-GI [protein 15% , carbohydrate 55%, GI ≥ 56]) and two exercise interventions (high intensity [79–90% of maximum heart rate for 75 min/week, e.g. running] versus moderate intensity [60–75% of maximum heart rate for 150 min/week, e.g. brisk walking] for a total of 148 weeks. The aim of this period was to prevent T2D by maintaining the initial weight loss and by independent metabolic effects of diet and physical activity. Randomisation was stratified by gender and age group (25–45, 46–54 and 55–70 years of age) ensuring an even distribution of gender and age group over the four intervention arms in each centre.¹⁰

Researchers conducted 7 Clinical Investigation Days (CID) throughout the study using data collected from blood tests, urine samples, diaries, body composition assessments, and accelerometers. In addition, instructors led 17 group visits during the trial to support participants, including nutrition counselling and physical activity. The CID assessments and group visits were conducted within university settings or associated clinics. The study was conducted in a ‘real-life’ setting without daily supervision from researchers. The primary endpoint of the study was the incidence of T2D in the adults during 3 years according to diet (high protein/low-GI versus moderate protein/moderate-GI, adjusted for physical activity), based on a 75 g OGTT and/or HbA1c.¹⁰

At the end of the study, 962 patients remained in the trial. The results found no difference between the diet or exercise interventions in patients following the initial weight loss phase. The 3-year incidence rate of T2D in patients with prediabetes and initial weight loss prediabetes was only 4%. Researchers estimated that without any intervention, about 21% would have been diagnosed with T2D. After the initial weight loss, 35% of patients who initially lost at least 8% body weight were no longer considered to have prediabetes. After 3 years, 18.5% of those who had completed the program no longer had prediabetes.¹⁰

One limitation of the study was the fact that over half (56.2%) of the participants discontinued the study between the initial weight-loss phase and the study’s endpoint, highlighting the importance of coaching and support. It would also be useful to further assess the trend of fasting glucose among patients, which typically dropped immediately during the weight-loss phase, then gradually increased over the following 3 years.¹⁰

Lead investigator, Ian Macdonald, Professor of Metabolic Physiology at the University of Nottingham, commented: ‘Further work is needed to explore the reasons for such successful prevention of type 2 diabetes; however, it is likely that the initial weight loss combined with thorough education and support in the components in either nutrition plan, in addition to a physical activity program, led to successful lifestyle changes and maintenance of at least some of the initial weight loss in most of the people completing the trial. The inclusion of an initial period of a low-calorie diet achieving significant weight loss, preceding a well-structured and effectively delivered weight maintenance program, may be a major feature of future diabetes prevention programs’.¹⁰

Overall, Professor MacDonald considered the initial PREVIEW data to be successful in comprehensively preventing the development of T2D in at-risk patients through lifestyle modification and weight loss.

<1>References

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