Role of Weight Loss Induced Prediabetes Remission in the Prevention of Type 2 Diabetes – Time to Improve Diabetes Prevention

Abstract Aims/hypothesis For individuals with prediabetes, the current American Diabetes Association (ADA) guidelines recommend a body weight loss >7% to prevent the development of type 2 diabetes (T2D) without any glycemic target goals. However, we have recently shown that weight loss induced prediabetes remission reduces relative T2D risk by 73% within the following two years. Therefore, we investigated relative T2D risk reduction in people with weight loss vs those with weight loss and prediabetes remission in an independent cohort: the randomized controlled Diabetes Prevention Program (DPP). Methods Individuals who lost >7% of their body weight over the first year were included in this analysis. Of these, 416 were assigned to intensive lifestyle intervention and 64 received placebo. Remission of prediabetes was defined by normalization of fasting and 2h glucose during an oral glucose tolerance test and a normalized HbA1c according to ADA criteria. Non-remission was given when at least one of these criteria was not met. We computed Kaplan-Meier curves and compared them using log-rank tests and future T2D risk was assessed by computing the relative risk between groups. Results In DPP, 480 individuals achieved a weight loss of >7% and of these 114 additionally achieved prediabetes remission. Over the period of 6 years, those who achieved weight loss and remission had a 66% lower relative risk to develop T2D compared to those who only met the 7% weight loss goal RR=0.34, 95% CI (0.15, 0.76). Similarly, weight loss responders had a lower relative future T2D risk compared to weight loss non-responders RR=0.28, 95% CI (0.13, 0.64). Importantly, there was only a single T2D case in weight loss responders for up to 4 years after the intervention. Conclusions/interpretation The combination of achieving weight loss goals and prediabetes remission is most effective in reducing future T2D risk. Thus, beside weight loss goals, interventions in individuals with prediabetes should be continued until prediabetes remission is achieved and this ought to be adapted in current clinical praxis guidelines.