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

Diabetologia. 2015 Dec;58(12):2791-9. doi: 10.1007/s00125-015-3750-1. Epub 2015 Sep 29.


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: NCT00072995.

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

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Body Weight
  • Cholestanetriol 26-Monooxygenase / genetics
  • Cytochrome P450 Family 2
  • Diet, Protein-Restricted
  • Dietary Proteins / pharmacology*
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Insulin / blood
  • Insulin Resistance / genetics*
  • Male
  • Middle Aged
  • Obesity / diet therapy
  • Obesity / genetics
  • Overweight / diet therapy
  • Overweight / genetics
  • Polymorphism, Single Nucleotide
  • Treatment Outcome
  • Vitamin D / metabolism*
  • Weight Loss / genetics*


  • Blood Glucose
  • Dietary Proteins
  • Insulin
  • Vitamin D
  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • Cholestanetriol 26-Monooxygenase

Associated data