TY - JOUR
T1 - HNF1A variant, energy-reduced diets and insulin resistance improvement during weight loss
T2 - The POUNDS Lost trial and DIRECT
AU - Huang, Tao
AU - Wang, Tiange
AU - Heianza, Yoriko
AU - Sun, Dianjianyi
AU - Ivey, Kerry
AU - Durst, Ronen
AU - Schwarzfuchs, Dan
AU - Stampfer, Meir J.
AU - Bray, George A.
AU - Sacks, Frank M.
AU - Shai, Iris
AU - Qi, Lu
N1 - Funding Information:
This study was supported by grants from the National Heart, Lung, and Blood Institute (HL071981), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718), the National Cancer Institute (CA155626), the General Clinical Research Center (RR-02635) and the Boston Obesity Nutrition Research Center (DK46200). Dr Lu Qi was a recipient of the American Heart Association Scientist Development Award (0730094N). DIRECT was supported by the Binational Science Foundation and the Robert C. and Veronica Atkins Foundation.
Funding Information:
We thank the participants of the POUNDS Lost trial and DIRECT for their contribution to the study. This study was supported by grants from the National Heart, Lung, and Blood Institute (HL071981), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718), the National Cancer Institute (CA155626), the General Clinical Research Center (RR-02635) and the Boston Obesity Nutrition Research Center (DK46200). Dr Lu Qi was a recipient of the American Heart Association Scientist Development Award (0730094N). DIRECT was supported by the Binational Science Foundation and the Robert C. and Veronica Atkins Foundation. None declared. T. H. and L. Q. designed the study and wrote the first draft. T. H. and T. W. analysed the data. T. H., T. W., Y. H., D. S., K. I., I. S., R. D., D. S., M. J. S., G. A. B., F. M. S. and L. Q. were involved in data collection. T. H. and L. Q. are guarantors. All authors contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content and approved the final version of the manuscript.
PY - 2018/6
Y1 - 2018/6
N2 - Aim: To determine whether weight-loss diets varying in macronutrients modulate the genetic effect of hepatocyte nuclear factor 1α (HNF1A) rs7957197 on weight loss and improvement of insulin resistance. Materials and methods: We analysed the interaction between HNF1A rs7957197 and weight-loss diets with regard to weight loss and insulin resistance improvement among 722 overweight/obese adults from a 2-year randomized weight-loss trial, the POUNDS Lost trial. The findings were replicated in another independent 2-year weight-loss trial, the Dietary Intervention Randomized Controlled Trial (DIRECT), in 280 overweight/obese adults. Results: In the POUNDS Lost trial, we found that a high-fat diet significantly modified the genetic effect of HNF1A on weight loss and reduction in waist circumference (P for interaction =.006 and.005, respectively). Borderline significant interactions for fasting insulin and insulin resistance (P for interaction =.07 and.06, respectively) were observed. We replicated the results in DIRECT. Pooled results showed similar significant interactions with weight loss, waist circumference reduction, and improvement in fasting insulin and insulin resistance (P values for interaction =.001,.005,.02 and.03, respectively). Greater decreases in weight, waist circumference, fasting insulin level and insulin resistance were observed in participants with the T allele compared to those without the T allele in the high-fat diet group (P =.04,.03 and.01, respectively). Conclusions: Our replicable findings provide strong evidence that individuals with the HNF1A rs7957197 T allele might obtain more benefits in weight loss and improvement of insulin resistance by choosing a hypocaloric and high-fat diet.
AB - Aim: To determine whether weight-loss diets varying in macronutrients modulate the genetic effect of hepatocyte nuclear factor 1α (HNF1A) rs7957197 on weight loss and improvement of insulin resistance. Materials and methods: We analysed the interaction between HNF1A rs7957197 and weight-loss diets with regard to weight loss and insulin resistance improvement among 722 overweight/obese adults from a 2-year randomized weight-loss trial, the POUNDS Lost trial. The findings were replicated in another independent 2-year weight-loss trial, the Dietary Intervention Randomized Controlled Trial (DIRECT), in 280 overweight/obese adults. Results: In the POUNDS Lost trial, we found that a high-fat diet significantly modified the genetic effect of HNF1A on weight loss and reduction in waist circumference (P for interaction =.006 and.005, respectively). Borderline significant interactions for fasting insulin and insulin resistance (P for interaction =.07 and.06, respectively) were observed. We replicated the results in DIRECT. Pooled results showed similar significant interactions with weight loss, waist circumference reduction, and improvement in fasting insulin and insulin resistance (P values for interaction =.001,.005,.02 and.03, respectively). Greater decreases in weight, waist circumference, fasting insulin level and insulin resistance were observed in participants with the T allele compared to those without the T allele in the high-fat diet group (P =.04,.03 and.01, respectively). Conclusions: Our replicable findings provide strong evidence that individuals with the HNF1A rs7957197 T allele might obtain more benefits in weight loss and improvement of insulin resistance by choosing a hypocaloric and high-fat diet.
UR - http://www.scopus.com/inward/record.url?scp=85043331610&partnerID=8YFLogxK
U2 - 10.1111/dom.13250
DO - 10.1111/dom.13250
M3 - Article
C2 - 29424957
AN - SCOPUS:85043331610
SN - 1462-8902
VL - 20
SP - 1445
EP - 1452
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 6
ER -