A Novel Diet-Phenotype Interaction Affecting Body Weight
A Novel Diet-Phenotype Interaction Affecting Body Weight
The primary aim of the study is to examine insulin secretion as an effect modifier of the
 efficacy of a low-fat vs. low-glycemic load diet for weight loss among overweight/obese young
 adults in an 18-month, prospectively stratified, multi-center randomized controlled trial.
In recent years, diets of widely varying composition have been used in the treatment of
 obesity. While none of these diets has produced consistent, long-term weight loss, some
 individuals on virtually all types of diets do remarkably well. One explanation for this
 variation among individuals is differences in motivation and behavior. However, underlying
 biological differences may also play an important role. Previous work has identified insulin
 secretion (as quantified by serum insulin concentration at 30 minutes following a standard
 75-gram oral glucose load) as an important biological determinant. This
 randomized-controlled, multi-center trial aims to test the hypothesis that insulin secretion
 will predict which type of diet will work best for each individual. A total of 160 obese
 young adults (18 to 40 years) will be assigned to one of two diets: low-fat (60%
 carbohydrate, 20% fat, 20% protein) or low-glycemic load (45% carbohydrate, 35% fat, 20%
 protein). Participants will be enrolled at two sites (Children's Hospital Boston or
 University of North Carolina-Chapel Hill) and assigned to diet groups according to baseline
 insulin secretion status. The protocol will include an intensive 6-month intervention period
 and a 12-month follow-up period. Registered dietitians will provide nutrition education and
 behavioral counseling during group workshops and scheduled telephone calls. In an effort to
 avoid confounding, close attention will be paid to control for treatment intensity, physical
 activity prescriptions, and behavioral methods between groups. The primary endpoint will be
 percent body fat by DXA scan. Secondary endpoints will include cardiovascular and diabetes
 risk factors. Repeated, 24-hour dietary and physical activity recall interviews will provide
 process data. Metabolomic profiling and molecular analysis of identified metabolites will be
 conducted to characterize phenotype and explore potential physiological mechanisms. A
 successful outcome of this work will inform the practice of "personalized" nutritional
 therapy, enhancing the ability to select the most efficacious weight loss diet for an
 individual based on underlying biological differences.
Inclusion Criteria

 -  Aged 18 to 40 years.

 -  Body mass index (BMI) ≥ 27 kg/m2.

 -  Body weight ≤ 300 lb.

 -  Access to a working telephone.

 -  Clearance in writing from a primary care provider (i.e., physician or nurse
 practitioner) to rule out pre-existing medical conditions.

 -  Willing and able to attend group workshops (for dietary intervention) on specified
 evenings.

 Exclusion Criteria

 -  Physician diagnosis of a major medical illness or eating disorder.

 -  Chronic use of any medication that may affect study outcomes (e.g.,
 insulin-sensitizing agents).

 -  Current smoking (i.e., 1 cigarette in the past week).

 -  Physical, mental, or cognitive handicaps that prevent participation.

 -  Another member of the family (i.e., first degree relative) or household participating
 in the study.

 -  Planning to relocate from current area of residence during the proposed timeframe for
 study participation.

 -  If female, planning to become pregnant during the 18 months of the study.