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Background:  Weight gain is associated with deterioration in metabolic health, whereas weight loss improves insulin sensitivity. This study assesses the impact of long-term, successfully maintained weight loss and weight-loss relapse on measures of insulin sensitivity and identifies factors that explain variability in insulin sensitivity.    Methods:  Women (20–45 years) were recruited into four groups: reduced-overweight/obese (RED,  n =15); body mass index (BMI)-matched controls (stable low-weight,  n =19), BMI⩽27 kg m −2 ; relapsed-overweight/obese subjects (REL,  n =11); and BMI-matched controls (obese stable weight,  n =11), BMI⩾27 kg m −2 . A 75 g oral glucose tolerance test determined fasting and 2 h plasma glucose and insulin. Homeostatic Model Assessment (HOMA-IR) and insulin sensitivity index (ISI (0,120) ) assessed insulin sensitivity. Anthropometric measurements, fasting resting metabolic rate (RMR) and respiratory quotient (RQ) were measured. Questionnaires and dietary intake were recorded, and physical activity was measured using accelerometers.    Results:  RED were more insulin sensitive, characterised by lower fasting ( P =0.001) and 2 h insulin ( P =0.003) levels compared with all other groups. There were no significant differences in dietary intake, sedentary, light and moderate activity, RMR or RQ in the RED compared with the other three groups. % Body weight (BW) lost ( P <0.001), % BW regained ( P <0.05), body fat %, light activity ( P <0.05, only log HOMA), vigorous activity ( P <0.05) and RQ ( P <0.01) predicted 61.4% and 59.7% of variability in log HOMA and log ISI (0,120) , respectively, in multiple linear regression models.    Conclusion:  This study showed sustained enhanced insulin sensitivity in successful weight loss maintainers compared with BMI-matched controls with no weight loss history. Weight-loss-relapsed individuals were indistinguishable from controls. Weight loss itself was the strongest predictor of improved insulin sensitivity, whereas weight regain significantly predicted reduced insulin sensitivity. Weight-loss maintenance programs are essential to retaining metabolic benefits acquired through weight loss. Being physically active, reducing sedentary behaviour and, in particular, including small amounts of vigorous physical activity significantly predicted improved insulin sensitivity.

Enhanced insulin sensitivity in successful, long-term weight loss maintainers compared with matched controls with no weight loss history