Low circulating IGF-II concentrations predict weight gain and obesity in humans.

Results from experimental and gene-association studies suggest that IGF-II may influence body weight regulation and that individuals with low IGF-II levels may be more susceptible to weight gain and obesity. We therefore assessed the association between circulating concentrations of IGF-II and subsequent weight gain and progression to obesity. Participants in this study were 463 nonobese men and women aged between 45 and 60 years with normal glucose tolerance and with metabolic and anthropometric assessments at baseline and follow-up clinic visits. We examined the association between baseline concentrations of fasting serum IGF-II and risk of gaining > or =2.5 kg body wt or developing obesity using unconditional logistic regression. A total of 217 participants gained > or =2.5 kg body wt, and 29 developed obesity after >4 years of follow-up. In multivariate analysis, baseline IGF-II levels were significantly lower in participants who subsequently gained weight compared with individuals who remained stable or lost weight (P = 0.010). Similarly, individuals who developed obesity had lower baseline IGF-II levels (P = 0.006). Relatively higher IGF-II levels were also associated with a reduced risk of gaining weight (P for trend across quintiles of IGF-II = 0.006). Our data suggest that circulating IGF-II levels may play a role in body weight regulation and development of obesity in men and women with normal glucose tolerance.