Vitamin D metabolism-related genetic variants, dietary protein intake and improvement of insulin resistance in a 2 year weight-loss trial: POUNDS Lost

Abstract

Aims/hypothesis: Vitamin D and related genetic variants are associated with obesity and insulin resistance. We aimed to examine whether vitamin D metabolism-related variants affect changes in body weight and insulin resistance in response to weight-loss diets varying in macronutrient content.

Methods: Three vitamin D metabolism-related variants, DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs2282679, were genotyped in 732 overweight/obese participants from a 2 year weight-loss trial (POUNDS Lost). We assessed genotype effects on changes in body weight, fasting levels of glucose and insulin, and HOMA-IR at 6 months (up to 656 participants) and 2 years (up to 596 participants) in response to low-protein vs high-protein diets, and low-fat vs high-fat diets.

Results: We found significant interactions between DHCR7 rs12785878 and diets varying in protein, but not in fat, on changes in insulin and HOMA-IR at both 6 months (p for interaction <0.001) and 2 years (p for interaction ≤ 0.03). The T allele (vitamin-D-increasing allele) of DHCR7 rs12785878 was associated with greater decreases in insulin and HOMA-IR (p < 0.002) in response to high-protein diets, while there was no significant genotype effect on changes in these traits in the low-protein diet group. Generalised estimating equation analyses indicated significant genotype effects on trajectory of changes in insulin resistance over the 2 year intervention in response to high-protein diets (p < 0.001). We did not observe significant interaction between the other two variants and dietary protein or fat on changes in these traits.

Conclusions/interpretation: Our data suggest that individuals carrying the T allele of DHCR7 rs12785878 might benefit more in improvement of insulin resistance than noncarriers by consuming high-protein weight-loss diets.

Trial registration: ClinicalTrials.gov NCT00072995.

Keywords: Diet intervention; Genetic variants; Insulin resistance; Vitamin D; Weight loss.

Figures

Fig. 1

Changes in insulin (a, b) and HOMA-IR (c, d) by DHCR7 rs12785878 genotype in response to low-protein diets and high-protein diets at 6 months and 2 years. Black bars, DHCR7 rs12785878 TT genotype; grey bars, DHCR7 rs12785878 TG genotype; white bars, DHCR7 rs12785878 GG genotype. Dara are means ± SE, adjusted for age, sex, ethnicity and baseline value for the respective outcome traits. p=0.0008 and 0.03 for interactions between DHCR7 rs12785878 and diet intervention on changes in fasting insulin at 6 months (a) and 2 years (b), respectively. p=0.0009 and 0.02 for interactions between DHCR7 rs12785878 and diet intervention on changes in HOMA-IR at 6 months (c) and 2 years (d), respectively. †p=0.0009 and ‡p=0.002 for genotype effects on changes in insulin (a) and HOMA-IR (c), respectively, at 6 months in the high-protein diet groups

Fig. 2

Trajectory of changes in insulin and HOMA-IR by DHCR7 rs12785878 genotype in response to low-protein diets (a, c) and high-protein diets (b, d) over a 2 year intervention. Black circle and solid line, DHCR7 rs12785878 TT genotype; grey circle and dashed line, DHCR7 rs12785878 TG genotype; white circle and dotted line, DHCR7 rs12785878 GG genotype. Data are means ± SE, adjusted for age, sex, ethnicity and baseline value for the respective outcome traits. †p<0.0001 and ‡p=0.0009 for genotype effects on changes in insulin (b) and HOMA-IR (d), respectively, in the high-protein diet groups