Enduring improvements in hepatic insulin sensitivity predict sustained remission of prediabetes during a 3-year lifestyle intervention: results from the PREVIEW multinational diabetes prevention trial

BACKGROUND: Recent investigation advocates the use of prediabetes remission as a goal of diabetes prevention. We aimed to compare changes in metabolic markers in participants with and without sustained remission of prediabetes during a 3-year lifestyle intervention. METHODS: This post-hoc analysis used data from the PREVIEW trial, a 3-year, multinational, multicenter, randomized controlled trial aiming to examine the effects of lifestyle interventions on prevention of type 2 diabetes among high-risk adults. Adult participants with prediabetes and overweight/obesity underwent 8-weeks of rapid weight loss followed by a 148-week lifestyle intervention for weight loss maintenance. Participants who completed the full protocol and had available data (n = 846) were included in the current analysis. Participants were classified into prediabetes maintainers, relapsers, and non-responders according to blood glucose levels at 1 and 3 years. Changes in metabolic markers over 3 years were compared in those who achieved sustained remission (maintainers, n = 102) vs those who failed (non-responders, n = 618), as well as those who were successful at 1 year but then relapsed (relapsers, n = 126). RESULTS: Only 12% participants experienced sustained remission at 3 years. After adjusting for baseline covariates, compared with non-responders, maintainers achieved greater weight loss (mean difference -4.0 kg; 95% CI -5.8, -2.2 kg) and fat mass loss at 3 years. Maintainers also made further improvements in markers of hepatic insulin sensitivity, regardless of weight change. Compared with relapsers, maintainers had greater decreases in weight and fat mass, but changes in visceral adiposity index were similar. Relapsers gradually reverted to an insulin resistant state at 2 and 3 years compared with maintainers, independent of weight change. CONCLUSIONS: In a long-term lifestyle intervention, sustained remission of prediabetes was associated with enduring improvements in hepatic insulin sensitivity, regardless of weight change. In addition to weight loss, targeting hepatic insulin sensitivity per se may help prevent relapse in prediabetes.