Persistence of improvement in insulin sensitivity following a dietary weight loss programme

Short-term dietary weight loss can improve insulin resistance but long-term studies are lacking. We sought to quantify the degree to which maintenance of weight loss after a short-term dietary intervention was associated with persistent metabolic benefits.

Fifty-seven insulin-resistant obese subjects had insulin-mediated glucose disposal quantified through the steady-state plasma glucose (SSPG) test, and associated metabolic risk markers quantified at baseline, after a 16-week dietary weight loss intervention, and in 25 subjects, at follow-up of 28.8 +/- 13 months. Changes in metabolic variables over time were analysed and correlation with weight loss ascertained. Those with greatest vs. least long-term SSPG response (responders vs. non-responders) were compared. Multivariate analysis was performed for predictors of persistent SSPG response.

At follow-up, the 25 subjects who returned for metabolic testing had, on average, maintained their weight loss. Insulin-mediated glucose disposal remained significantly improved vs. baseline, as did plasma triglyceride and HDL cholesterol (HDL-C) concentrations, and improvement correlated with total amount of weight lost. Comparison of SSPG responders to non-responders showed no difference in amount of weight lost and SSPG change during the 16-week dietary intervention; however, SSPG non-responders regained 2.6% of weight lost, whereas responders lost an additional 1.5% at follow-up (p < 0.05 vs. non-responders). Non-responders had baseline characteristics consistent with more severe insulin resistance, including higher fasting plasma glucose (p = 0.03). Long-term SSPG change was independently predicted by both total weight loss (p = 0.005) and baseline fasting plasma glucose (p = 0.007).

Improvement in insulin sensitivity is maintained for 2-3 years following dietary weight loss if weight is not regained. Triglyceride and HDL-C concentrations also remain improved over time, consistent with improvement in insulin sensitivity. Fasting glucose and weight regain predict less long-term response in insulin sensitivity. These results highlight the potential long-term benefits of weight loss and importance of preventing weight regain among high-risk individuals.