Evidence for the carbohydrate–insulin model in a reanalysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial

Abstract

BackgroundThe Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial demonstrated that meaningful weight loss can be achieved with either a “healthy low-carbohydrate diet” (LCD) or “healthy low-fat diet” (LFD). However, because both diets substantially decreased glycemic load (GL), the dietary factors mediating weight loss remain unclear. ObjectivesWe aimed to explore the contribution of macronutrients and GL to weight loss in DIETFITS and examine a hypothesized relationship between GL and insulin secretion. DesignThis study is a secondary data analysis of the DIETFITS trial, in which participants with overweight or obesity (aged 18–50 y) were randomized to a 12-mo LCD (N = 304) or LFD (N = 305). ResultsMeasures related to carbohydrate intake (total amount, glycemic index, added sugar, and fiber) showed strong associations with weight loss at 3-, 6-, and 12-mo time points in the full cohort, whereas those related to total fat intake showed weak to no associations. A biomarker of carbohydrate (triglyceride/HDL cholesterol ratio) predicted weight loss at all time points (3-mo: β [kg/biomarker z-score change] = 1.1, P = 3.5 × 10−9; 6-mo: β = 1.7, P = 1.1 × 10−9; and 12-mo: β = 2.6, P = 1.5 × 10−15), whereas that of fat (low-density lipoprotein cholesterol + HDL cholesterol) did not (all time points: P = NS). In a mediation model, GL explained most of the observed effect of total calorie intake on weight change. Dividing the cohort into quintiles of baseline insulin secretion and GL reduction revealed evidence of effect modification for weight loss, with P = 0.0009 at 3 mo, P = 0.01 at 6 mo, and P = 0.07 at 12 mo. ConclusionsAs predicted by the carbohydrate–insulin model of obesity, weight loss in both diet groups of DIETFITS seems to have been driven by the reduction of GL more so than dietary fat or calories, an effect that may be most pronounced among those with high insulin secretion. These findings should be interpreted cautiously in view of the exploratory nature of this study. Trial RegistrationClinicalTrials.gov (NCT01826591).