Comment on Rooney et al. Global Prevalence of Prediabetes. Diabetes Care 2023;46:1388–1394

The International Diabetes Federation (IDF) has been reporting the global prevalence of impaired glucose tolerance (IGT) since 2003. For the first time, the IDF has estimated the worldwide prevalence of impaired fasting glucose (IFG), in the article by Rooney et al. (1). Using data from 50 high-quality studies from 43 countries, the age-adjusted prevalence of IGT among adults aged 20–79 years worldwide was estimated to be 9.1% (464 million) in 2021. The corresponding estimate for IFG was 5.8% (298 million) in 2021 based on data from 43 high-quality studies from 40 countries. Of note, ∼40% of the world population was represented in IGT data sources compared with only 18% in studies of IFG. Studies show that 55–70% of individuals with IFG do not have IGT (1), the so-called isolated IFG (i-IFG). These figures translate to 163.9–208.6 million adults with i-IFG worldwide. Despite this enormous burden of i-IFG, it is a highly understudied prediabetes phenotype with regard to the prevention of type 2 diabetes.

i-IFG is characterized by fasting hyperglycemia due to impaired early-phase insulin secretion and hepatic insulin resistance (2). People with i-IFG are at elevated risk of type 2 diabetes, vascular complications, and mortality (2). However, to date, there are no proven effective lifestyle interventions to prevent type 2 diabetes in individuals with i-IFG (2). Improving diet quality by reducing saturated fat intake and increasing fiber intake with a modest reduction in calories (500–750 fewer calories a day) and increasing aerobic physical activity are ineffective in reducing diabetes incidence in those with i-IFG (3). These lifestyle change strategies improve β-cell function and peripheral insulin resistance, the pathophysiological defects of IGT, but not hepatic insulin resistance that characterizes i-IFG (2). Thus, it is essential to evaluate the efficacy of different forms of lifestyle interventions such as low-calorie diets (LCDs) in individuals with i-IFG.

LCDs (800–1,500 kcal/day) are highly effective in improving β-cell function and reducing hepatic insulin resistance in people with type 2 diabetes (4). However, the efficacy of LCDs has been examined scarcely in individuals with i-IFG, who share the same pathophysiological defects as those in people with type 2 diabetes (2). One of the first pieces of evidence comes from a post hoc analysis of the PREVIEW (Prevention of Diabetes Through Lifestyle Interventions and Population Studies in Europe and Around the World) study (5). PREVIEW was conducted among 869 overweight (BMI ≥25 kg/m²) individuals (aged 25–70 years) with i-IFG. After an 8-week LCD (810 kcal/day, with 41.2% from carbohydrate, 43.7% protein, and 15.1% fat) phase, the mean weight loss was 10 kg (10% of the initial body weight), which was associated with a reduction in mean fasting plasma glucose of 6 mg/dL (5). While these results are promising, the effects of LCDs in i-IFG need to be tested in randomized controlled trials in a more structured way with incorporation of stepped food reintroduction and a long-term weight loss–maintenance phase.

It is high time we develop targeted lifestyle interventions for people with i-IFG to help control the growing diabetes pandemic globally.