A Novel Diet-Phenotype Interaction Affecting Body Weight

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.