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

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.

Figure 1.. Flow of Participants Through the Diet Intervention Examining The Factors Interacting with Treatment Success Trial

^aBody mass index is calculated as weight in kilograms divided by height in meters squared. ^bTo convert glucose to mmol/L, multiply by 0.0555.

Figure 2.. Interaction Among Diet and Genotype and Diet and Insulin-30 Tertile at Baseline and 12-Month Weight Loss

The black solid circle indicates the mean, the left and right borders of the box mark the first and third quartiles, the black vertical line indicates the median, the error bars indicate the 5th and 95th percentiles, and the hollow circles indicate the individuals whose values were outside the 5th or 95th percentiles. The No. of participants reflect data for the individuals who had weight data at both baseline and 12 months. Statistical analyses include data from all individuals randomized (described in the Statistical Analysis section). A, Three-way interaction term among diet, genotype, and the 12-month time point was not statistically significant (beta coefficient, 1.38 [95% CI, −0.72 to 3.49]; P = .20). As described in Stanton et al, of all the possible combinations of variance in 3 single-nucleotide polymorphism multilocus genotype patterns, some were considered consistent with the low-fat genotype pattern, some with the low-carbohydrate genotype pattern, and some with neither of these 2 genotype patterns. By design, as described in the initial National Institutes of Health grant application, those individuals with neither of the main 2 genotype patterns were not included in the main analyses. There were 39 participants who had compromised or missing DNA. B, Three-way interaction term among diet, insulin, and the 12-month time point was not statistically significant (beta coefficient for 10-μIU/mL increase in insulin, 0.08 [95% CI, −0.13 to 0.28]; P = .47). Insulin-30 is the blood concentration of insulin 30 minutes after consuming 75 g of glucose as part of a standard oral glucose tolerance test. Insulin-30 was treated as a continuous variable in the statistical model. Tertiles were used in this Figure for ease of presentation. The mean for the lowest tertile was 40.8 μIU/mL (range, 7.3-60.6 μIU/mL); middle, 80.1 μIU/mL (range, 60.7-103.1 μIU/mL); and highest, 159.6 μIU/mL (range, 103.4-562.5 μIU/mL).