A novel interaction between dietary composition and insulin secretion: effects on weight gain in the Quebec Family Study

Am J Clin Nutr. 2008 Feb;87(2):303-9. doi: 10.1093/ajcn/87.2.303.


Background: Clinical trials of low-fat diets characteristically produce small mean long-term weight loss but a large interindividual variation in response. This variation has been attributed to psychological and behavioral factors, although biological differences may also play a role.

Objective: The objective was to determine whether physiologic differences in insulin secretion explain differences in weight gain among individuals consuming low- and high-fat diets.

Design: Of 276 individuals followed in the Quebec Family Study for a mean of 6 y, we compared those in the lowest with those in the highest dietary fat tertiles. We performed oral-glucose-tolerance tests at baseline and examined the insulin concentration at 30 min (insulin-30) as a proxy measure of insulin secretion. Six-year changes in body weight and waist circumference were the primary endpoints. We determined the associations between insulin-30 and the primary endpoints by linear regression analysis, with adjustment for potentially confounding factors.

Results: Mean changes in body weight and waist circumference did not differ significantly between the lowest- and highest-fat diet groups. However, these endpoints were strongly associated with insulin-30, especially among individuals consuming the lowest-fat diet. Insulin-30 at baseline was significantly associated with 6-y weight gain (r = 0.51, P < 0.0001) and change in waist circumference (r = 0.55, P < 0.0001) in the lowest diet fat, group [corrected], but not in the highest diet fat group (r = 0.18, P = 0.086 and r = 0.20, P = 0.058, respectively) [corrected] Individuals in the highest insulin-30 and lowest dietary fat group gained 1.8 kg more than did those in the highest insulin-30 and highest dietary fat group (51%; P = 0.034); they gained 4.5 kg more than did those in the lowest insulin-30 and lowest dietary fat group (6.5-fold; P = 0.0026).

Conclusion: A proxy measure of insulin secretion strongly predicts changes in body weight and waist circumference over 6 y in adults, especially among those consuming lower-fat diets, which demonstrates the existence of a novel diet-phenotype interaction.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Diet, Fat-Restricted*
  • Dietary Carbohydrates / administration & dosage*
  • Dietary Fats / administration & dosage*
  • Female
  • Glucose Tolerance Test
  • Glycemic Index
  • Humans
  • Insulin / blood*
  • Insulin / metabolism
  • Insulin Secretion
  • Male
  • Middle Aged
  • Phenotype
  • Predictive Value of Tests
  • Quebec
  • Waist-Hip Ratio*
  • Weight Gain*


  • Dietary Carbohydrates
  • Dietary Fats
  • Insulin