ABSTRACT One-third of U.S. adults have prediabetes and are at high risk of developing type 2 diabetes and its devastating health consequences. The landmark Diabetes Prevention Program (DPP) trial demonstrated that a resource- intensive, one-on-one program combining diet and physical activity changes, could reduce the 3-year risk of type 2 diabetes by 58% compared with usual care. Consequently, the DPP is considered one of the best examples of how a nutritional program can prevent disease, and the Centers for Disease Control and Prevention (CDC) and others recommend the DPP as a first-line treatment for adults with prediabetes. The CDC’s National Diabetes Prevention Program (NDPP) is an adaptation of the DPP trial curriculum, using group-based delivery. It teaches participants to follow a low-fat, calorie-restricted diet, as this was the prevailing dietary advice when the DPP trial was designed over 30 years ago. The NDPP is now available at >1,500 sites throughout the United States and reimbursed by Medicare and other payors. Yet, despite widespread availability, only 36% of participants achieve the program goal of ≥5% body weight loss and, when measured, HbA1c reduces on average less than 0.1%. We hypothesize that adapting the NDPP to teach a different dietary strategy—a very-low-carbohydrate diet (VLCD)—will increase the effectiveness of the NDPP as a tool for type 2 diabetes risk reduction. Carbohydrate intake is the strongest factor impacting post-prandial glycemia, and a VLCD—due to its ability to reduce glycemia, weight, and the need for anti-hyperglycemic medications—is now recommended by the American Diabetes Association for treatment of type 2 diabetes. To date, there are neither high-quality, randomized controlled trials testing how effective a VLCD is at reducing the risk of type 2 diabetes among adults with prediabetes, nor randomized trials of VLCD versions of any DPP. To begin to fill this critical gap, our team has developed and pilot tested a VLCD version of the NDPP (VLC- NDPP), delivered by our CDC-recognized community partner, the National Kidney Foundation of Michigan. Our findings demonstrate that a VLC-NDPP is feasible and acceptable. We now propose to conduct a 12- month, 1:1, randomized trial that will assign 300 overweight or obese adults with prediabetes to either the standard NDPP or the VLC-NDPP. The primary outcome is glycemic control (measured by HbA1c), with secondary outcomes including body weight, body fat percentage, glycemic variability, and inflammation. We will also explore the barriers to and facilitators of glycemic control and dietary adherence using mixed methods. As the prevalence of type 2 diabetes and the understanding of personalized interventions continue to increase, there is a critical need to provide additional effective options for population-level type 2 diabetes prevention strategies. If the VLC-DPP shows promise, this trial would be a precursor to a multi-site trial with incidence of type 2 dia...