Wednesday, Mar 23, 2011, 8:45 AM -10:00 AM
Insulin Receptor Substrate 1 (IRS1) Gene Variation Modifies Insulin Resistance Response to Weight-Loss Diets in a Two-Year Randomized Trial
Atrium Ballroom A
Wednesday, Mar 23, 2011, 9:15 AM - 9:30 AM
+NPAM - Metabolism
Diet; Genetics; Insulin
, Frank Hu, Frank Sacks, Lu Qi, Harvard Sch of Public Health, Boston, MA
A genetic variant (rs29436410) in
was recently associated with type 2 diabetes risk, insulin resistance and hyperinsulinemia. We examined whether this variant interacts with 4 weight-loss diets in affecting insulin resistance.
We genotyped this variant in 763 overweight adults, who were randomly assigned to one of four diets for 2 years, from the Pounds Lost trial; the targeted percentages of energy derived from fat, protein and carbohydrate in the four diets were 20, 15 and 65%; 20, 25 and 55%; 40, 15, and 45%; 40, 25% and 35%. We assessed the effect of genotypes on changes in weight, fasting insulin and HOMA-IR at 6 months and 2 years in two-by-two factorial comparisons of low vs. high fat and average vs. high protein, and in the comparison of highest vs. lowest carbohydrate content.
At baseline, the C allele of rs29436410 was significantly associated with elevated fasting insulin (
=0.005) and HOMA-IR (
=0.006) in all participants. At 6 months, subjects with CC genotype had greater weight loss (
=0.01) and decreases in insulin (
=0.002) and HOMA-IR (
=0.004) compared to those with CT or TT genotypes in the highest carbohydrate (65% energy) diet group, while no significant genotype effect was observed in the other diet groups. There were significant interactions between the genotypes and diet groups with respect to weight loss, and change in insulin or HOMA-IR (all for interaction
<0.02, Figure 1). At 2 years, the effect of the genotypes became nonsignificant for weight loss (
for interaction =0.09), but remained significant for changes in insulin (
=0.007) and HOMA-IR (
=0.01) in the highest carbohydrate diet group (both
for interaction <0.02). Moreover, the effect of genotypes on changes in insulin and HOMA-IR in the high carbohydrate group persisted after adjustment for weight loss.
Our findings indicate that a high carbohydrate diet may be more effective in weight loss and reducing insulin resistance in subjects with
rs29436410 CC genotype than those without this genotype.
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