Effects of weight regain following intentional weight loss on glucoregulatory function in overweight and obese adults with pre-diabetes.

OBJECTIVE:To assess the extent to which initial, intentional weight loss-associated improvements in glucose tolerance and insulin action are diminished with weight regain. METHODS:138 overweight and obese (BMI: 32.4±3.9kg/m(2)), adults (59.0±9.7 years), with pre-diabetes were followed through a 6-month weight loss intervention and subsequent 18-month weight maintenance period, or usual care control condition. Longitudinal change in weight (baseline, 6, 24 months) was used to classify individuals into weight pattern categories (Loser/Maintainer (LM), n= 50; Loser/Regainer (LR), n=51; and Weight Stable (WS), n=37). Fasting plasma glucose (FPG), insulin, and insulin resistance (HOMA-IR) were measured at baseline, 6, 12, 18 and 24 months and model adjusted changes, by weight pattern category, were assessed. RESULTS:LMs and LRs lost 8.3±4.7kg (8.7±4.5%) and 9.6±4.7kg (10.2±4.7%) during the first 6 months, respectively. LM continued to lose 1.1±3.4kg over the next 18 months (9.9±6.5% reduction from baseline; p<0.05), while LRs regained 6.5±3.7kg (3.3±5.3% reduction from baseline; p<0.05). Weight change was directly associated with change in all DM risk factors (all p<0.01). Notably, despite an absolute reduction in body weight (from baseline to 24 months) achieved in the LR group, 24-month changes in FPG, insulin, and HOMA-IR did not differ between WS and LR groups. Conversely, LM saw sustained improvements in all measured DM risk factors. CONCLUSIONS:Significant weight loss followed by weight loss maintenance is associated with sustained improvements in FPG, insulin, and HOMA-IR; conversely, even partial weight regain is associated with regression of initial improvements in these risk factors towards baseline values.