Glucose homeostasis predicts weight gain: prospective and clinical evidence

The potential long-term impact of low glycaemia on body fat accumulation has not been verified. Therefore, we examined the effects of low glucose concentrations on long-term energy balance and weight gain in humans.Two sets of analyses were realized in order to verify this objective. First, Study 1 consisted of 259 participants between 20 and 65 years of age selected from Phase 2 of the Quebec Family Study (QFS). The association between glucose concentrations at the end of an oral glucose tolerance test (OGTT) and changes in body mass was analysed prospectively (mean follow-up of 6 years). In addition, Study 2 consisted of 44 obese participants (20 men and 24 women) randomly assigned to a 15-week weight loss program in either a drug therapy group (fenfluramine) or a placebo group coupled with energy intake restriction. The focus of this study was the relationship between glycaemic control at the end of the treatment and post-treatment weight regain.In Study 1, the glucose concentrations at 120 min of the OGTT were negatively correlated with weight gain over 6 years (r=-0.42, p<0.01). In Study 2, the weight loss program induced a mean reduction in body weight of 10 kg in the fenfluramine and placebo groups. In participants who returned for a follow-up visit (mean=81 weeks after the intervention), the glucose area below fasting values (GABF) at the end of the OGTT increased with weight loss (p<0.01) and was correlated with weight regain (r=0.74, p<0.01).Lower glucose concentrations at the end of an OGTT are correlated with weight gain over time. Large amounts of weight loss are associated with low glycaemia at the end of an OGTT. These low glucose concentrations are strong predictors of the amount of weight regained after weight loss.