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.

• Authors: Qibin Qi, Yan Zheng, Tao Huang, Jennifer Rood, George A Bray, Frank M Sacks, Lu Qi
• Journal: Diabetologia (Diabetologia) Vol. 58 Issue 12 Pg. 2791-9 (Dec 2015) ISSN: 1432-0428 [Electronic] Germany
• PMID: 26416604 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

• 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, genetics)
• Overweight (diet therapy, genetics)
• Polymorphism, Single Nucleotide
• Treatment Outcome
• Vitamin D (metabolism)
• Weight Loss (genetics)