PMID- 25504030
OWN - NLM
STAT- MEDLINE
DCOM- 20150909
LR  - 20181202
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Print)
IS  - 0149-5992 (Linking)
VI  - 38
IP  - 3
DP  - 2015 Mar
TI  - PCSK7 genotype modifies effect of a weight-loss diet on 2-year changes of insulin 
      resistance: the POUNDS LOST trial.
PG  - 439-44
LID - 10.2337/dc14-0473 [doi]
AB  - OBJECTIVE: A common variant rs236918 in the PCSK7 gene has the strongest 
      association with iron homeostasis and is related to insulin resistance. Dietary 
      carbohydrate (CHO) modulates the genetic effect on insulin resistance. We 
      examined whether 2-year weight-loss diets modify the effect of PCSK7 genetic 
      variants on changes in fasting insulin levels and insulin resistance in a 
      randomized, controlled trial. RESEARCH DESIGN AND METHODS: Data were analyzed in 
      the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial, 
      which is a randomized, controlled 2-year weight-loss trial using diets that 
      differed in macronutrient proportions. PCSK7 rs236918 was genotyped in 730 
      overweight or obese adults (80% whites) in this trial. We assessed the 
      progression in fasting insulin and glucose levels, and insulin resistance by 
      genotypes. RESULTS: During the 6-month weight-loss phase, the PCSK7 rs236918 G 
      allele was significantly associated with greater decreases in fasting insulin 
      levels in the high-dietary CHO group (P for interaction = 0.04), while the 
      interaction for changes in HOMA-insulin resistance (HOMA-IR) (P for interaction = 
      0.06) did not reach significant levels in white subjects. The G allele was 
      significantly associated with a greater decrease in fasting insulin levels and 
      HOMA-IR in response to high dietary CHO levels (P = 0.02 and P = 0.03, 
      respectively). From 6 months to 2 years (weight-regain phase), the interactions 
      became attenuated due to the regaining of weight (P for interactions = 0.08 and 
      0.06, respectively). In addition, we observed similar and even stronger results 
      in the whole-study samples from the trial. CONCLUSIONS: Our data suggest that 
      PCSK7 genotypes may interact with dietary CHO intake on changes in insulin 
      sensitivity in the white Americans.
CI  - (c) 2015 by the American Diabetes Association. Readers may use this article as long 
      as the work is properly cited, the use is educational and not for profit, and the 
      work is not altered.
FAU - Huang, Tao
AU  - Huang T
AD  - Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
FAU - Huang, Jinyan
AU  - Huang J
AD  - Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, 
      MA.
FAU - Qi, Qibin
AU  - Qi Q
AD  - Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
FAU - Li, Yanping
AU  - Li Y
AD  - Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 
      Channing Division of Network Medicine, Department of Medicine, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, MA.
FAU - Bray, George A
AU  - Bray GA
AD  - Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, 
      LA.
FAU - Rood, Jennifer
AU  - Rood J
AD  - Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, 
      LA.
FAU - Sacks, Frank M
AU  - Sacks FM
AD  - Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
FAU - Qi, Lu
AU  - Qi L
AD  - Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 
      Channing Division of Network Medicine, Department of Medicine, Brigham and 
      Women's Hospital and Harvard Medical School, Boston, MA 
      nhlqi@channing.harvard.edu.
LA  - eng
SI  - ClinicalTrials.gov/NCT00072995
GR  - HL-071981/HL/NHLBI NIH HHS/United States
GR  - R01 DK091718/DK/NIDDK NIH HHS/United States
GR  - P30 DK046200/DK/NIDDK NIH HHS/United States
GR  - DK-46200/DK/NIDDK NIH HHS/United States
GR  - R01 HL071981/HL/NHLBI NIH HHS/United States
GR  - DK-091718/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141212
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Dietary Carbohydrates)
RN  - 0 (Insulin)
RN  - E1UOL152H7 (Iron)
RN  - EC 3.4.21.- (PCSK7 protein, human)
RN  - EC 3.4.21.- (Subtilisins)
SB  - IM
MH  - Alleles
MH  - Body Weight/genetics
MH  - Diet, Reducing/methods
MH  - Dietary Carbohydrates/pharmacology
MH  - Fasting/metabolism
MH  - Female
MH  - Genotype
MH  - Homeostasis/genetics
MH  - Humans
MH  - Insulin/genetics/metabolism
MH  - Insulin Resistance/*genetics
MH  - Iron/metabolism
MH  - Male
MH  - Middle Aged
MH  - Overweight/diet therapy/*genetics
MH  - Subtilisins/*genetics
MH  - Weight Loss/genetics
PMC - PMC4876697
EDAT- 2014/12/17 06:00
MHDA- 2015/09/10 06:00
PMCR- 2016/03/01
CRDT- 2014/12/16 06:00
PHST- 2014/12/16 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/09/10 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - dc14-0473 [pii]
AID - 0473 [pii]
AID - 10.2337/dc14-0473 [doi]
PST - ppublish
SO  - Diabetes Care. 2015 Mar;38(3):439-44. doi: 10.2337/dc14-0473. Epub 2014 Dec 12.