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Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin SecretionThe DIETFITS Randomized Clinical Trial

Educational Objective
To learn whether genotype or insulin-glucose dynamics modify the effectiveness of weight loss diets.
1 Credit CME
Key Points

Question  What is the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change at 12 months and are these effects related to genotype pattern or insulin secretion?

Findings  In this randomized clinical trial among 609 overweight adults, weight change over 12 months was not significantly different for participants in the HLF diet group (−5.3 kg) vs the HLC diet group (−6.0 kg), and there was no significant diet-genotype interaction or diet-insulin interaction with 12-month weight loss.

Meaning  There was no significant difference in 12-month weight loss between the HLF and HLC diets, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss.

Abstract

Importance  Dietary modification remains key to successful weight loss. Yet, no one dietary strategy is consistently superior to others for the general population. Previous research suggests genotype or insulin-glucose dynamics may modify the effects of diets.

Objective  To determine the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss.

Design, Setting, and Participants  The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized clinical trial included 609 adults aged 18 to 50 years without diabetes with a body mass index between 28 and 40. The trial enrollment was from January 29, 2013, through April 14, 2015; the date of final follow-up was May 16, 2016. Participants were randomized to the 12-month HLF or HLC diet. The study also tested whether 3 single-nucleotide polymorphism multilocus genotype responsiveness patterns or insulin secretion (INS-30; blood concentration of insulin 30 minutes after a glucose challenge) were associated with weight loss.

Interventions  Health educators delivered the behavior modification intervention to HLF (n = 305) and HLC (n = 304) participants via 22 diet-specific small group sessions administered over 12 months. The sessions focused on ways to achieve the lowest fat or carbohydrate intake that could be maintained long-term and emphasized diet quality.

Main Outcomes and Measures  Primary outcome was 12-month weight change and determination of whether there were significant interactions among diet type and genotype pattern, diet and insulin secretion, and diet and weight loss.

Results  Among 609 participants randomized (mean age, 40 [SD, 7] years; 57% women; mean body mass index, 33 [SD, 3]; 244 [40%] had a low-fat genotype; 180 [30%] had a low-carbohydrate genotype; mean baseline INS-30, 93 μIU/mL), 481 (79%) completed the trial. In the HLF vs HLC diets, respectively, the mean 12-month macronutrient distributions were 48% vs 30% for carbohydrates, 29% vs 45% for fat, and 21% vs 23% for protein. Weight change at 12 months was −5.3 kg for the HLF diet vs −6.0 kg for the HLC diet (mean between-group difference, 0.7 kg [95% CI, −0.2 to 1.6 kg]). There was no significant diet-genotype pattern interaction (P = .20) or diet-insulin secretion (INS-30) interaction (P = .47) with 12-month weight loss. There were 18 adverse events or serious adverse events that were evenly distributed across the 2 diet groups.

Conclusions and Relevance  In this 12-month weight loss diet study, there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss. In the context of these 2 common weight loss diet approaches, neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom.

Trial Registration  clinicaltrials.gov Identifier: NCT01826591

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Article Information

Corresponding Author: Christopher D. Gardner, PhD, Stanford Prevention Research Center, Department of Medicine, Stanford University Medical School, 1265 Welch Rd, Stanford, CA 94305 (cgardner@stanford.edu).

Accepted for Publication: January 17, 2018.

Correction: This article was corrected on April 3, 2018, to change the units of measure for the lipid level rows in Table 3 from mmol/L to mg/dL and reverse the corresponding SI conversion factor instructions from divide to multiply. This article was corrected on April 24, 2018, to change the Nutrition Science Initiative funding description.

Author Contributions: Dr Gardner had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Gardner, Rigdon, Ioannidis, Desai, King.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Gardner, Trepanowski, Del Gobbo, Hauser, Rigdon, Desai.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Gardner, Del Gobbo, Hauser, Rigdon, Ioannidis, Desai.

Obtained funding: Gardner.

Administrative, technical, or material support: Gardner, Hauser, King.

Supervision: Gardner, Desai, King.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Funding/Support: This study was supported by grant 1R01DK091831 from the National Institute of Diabetes and Digestive and Kidney Diseases, funding from the Nutrition Science Initiative, grants 1K12GM088033 and T32HL007034 from the National Heart, Lung, and Blood Institute, and the Stanford Clinical and Translational Science Award.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the other funders.

Additional Contributions: This study would not have been possible without the work of the following individuals who were affiliated with Stanford University at the time of the study and who received compensation for their work: Jennifer Robinson, PhD, and Antonella Dewell, MS, RD (served as study coordinators), Rise Cherin, MS, RD, Susan Kirkpatrick, RD, CDE, Jae Berman, MS, RD, CSSD, Dalia Perelman, MS, RD, CDE, and Mandy Murphy Carroll, MPH, RD (health educators), Sarah Farzinkhou, MPH, Valerie Alaimo, BS, Margaret Shimer Lawton, MPH, and Diane Demis, BS (diet assessment team), Josephine Hau, MPH, RD, Erin Avery, MS, Alexandra Rossi, BS, Katherine Dotter, BS, RD, and Sarah Mummah, PhD (involved in recruitment, screening, blood sample management, innovation, and other tasks), Ariadna Garcia, MS, FeiFei Qin, MPH, and Vidhya Balasubramanian, MS (involved in statistical support), Alana Koehler, BA (administrative support), and Lucia Aronica, PhD, Jennifer Hartle, DrPH, MHS, CIH, Lisa Offringa, PhD, Kenji Nagao, PhD, Marily Oppezzo, PhD, MS, RD, Benjamin Chrisinger, MUEP, PhD, and Michael Stanton, PhD (aided various phases of the study). We also acknowledge the 609 study participants without whom this investigation would not have been possible.

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