In a sample of 276 men and women who participated in the Québec Family Study, Chaput et al. tested the hypothesis that insulin secretion at 30 minutes following a standardized oral glucose tolerance test (OGTT) might be an important predictor of weight gain. The study population was classified into tertiles of dietary fat intake and was followed for an average of 6 years. Diet was assessed using a 3 day record at baseline and year 6. Over the follow-up, insulin secretion was found to be significantly associated with weight gain and increases in waist circumference in participants in the lowest diet fat tertile. This finding was not observed in the top tertile of dietary fat intake. This study suggests a new diet-phenotype interaction in predicting weight gain and insulin concentrations after an OGTT, which may help clinicians individualize dietary prescription to prevent weight gain.