Qi Qibin, Zheng Yan, Huang Tao, Rood Jennifer, Bray George A, Sacks Frank M, Qi Lu
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Nutrition, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.
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.
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.
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.
ClinicalTrials.gov NCT00072995.
目的/假设：维生素D及相关基因变异与肥胖和胰岛素抵抗相关。我们旨在研究维生素D代谢相关变异是否会影响在宏量营养素含量不同的减肥饮食作用下体重和胰岛素抵抗的变化。
在一项为期2年的减肥试验（即“减重”试验）中的732名超重/肥胖参与者中，对三个维生素D代谢相关变异，即DHCR7基因的rs12785878、CYP2R1基因的rs10741657和GC基因的rs2282679进行基因分型。我们评估了在6个月（最多656名参与者）和2年（最多596名参与者）时，针对低蛋白与高蛋白饮食以及低脂与高脂饮食，这些基因型对体重变化、空腹血糖和胰岛素水平以及胰岛素抵抗稳态模型评估（HOMA-IR）的影响。
我们发现，在6个月时（交互作用p<0.001）和2年时（交互作用p≤0.03），DHCR7基因的rs12785878与蛋白质含量不同（而非脂肪含量不同）的饮食之间，在胰岛素和HOMA-IR变化方面存在显著交互作用。DHCR7基因的rs12785（维生素D增加等位基因）与高蛋白饮食作用下胰岛素和HOMA-IR的更大降幅相关（p<0.002），而在低蛋白饮食组中，这些性状的变化没有显著的基因型效应。广义估计方程分析表明，在为期2年的高蛋白饮食干预中，基因型对胰岛素抵抗变化轨迹有显著影响（p<0.001）。我们未观察到其他两个变异与饮食蛋白质或脂肪在这些性状变化上存在显著交互作用。
结论/解读：我们的数据表明，携带DHCR7基因rs12785878的T等位基因的个体，通过食用高蛋白减肥饮食，在改善胰岛素抵抗方面可能比非携带者受益更多。
ClinicalTrials.gov NCT00072995
