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

Aim: 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. Methods: 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. Results: 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). Conclusions: 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.