Protein Intake & Insulin Action

Insulin resistance, impaired pancreatic β-cell function, and diabetes are important
complications associated with obesity. Although excess energy intake and body fat
accumulation are considered the major culprits responsible for obesity-associated metabolic
abnormalities, it is possible that insulin resistance and impaired β-cell function are also
due to increased dietary protein intake.

Protein intake is ~15 to 25% greater in obese than lean adults and exceeds the current
Institute of Medicine Recommended Daily Allowance (RDA) of 0.8 g protein/kg body weight by
~75%. An increase in habitual protein intake of only 10 to 40%, assessed using dietary
recall methods, been shown to increase the risk of developing diabetes by up to 2.2 fold.
Additionally, the ability to stimulate glucose disposal during insulin infusion is reported
to be impaired in individuals consuming double the recommended protein intake as part of an
isoenergetic diet. However, it is not known whether decreasing protein intake can improve
insulin sensitivity and β-cell function in weight-stable, obese individuals.

Accordingly, obese men and women will be randomized to 8 weeks of treatment with a weight
maintaining diet containing either i) 0.8 g protein/kg body weight (as recommended by the
Institute of Medicine; protein restriction group)or ii) 1.4 g protein/kg body weight
(control group). All subjects will receive a standardized "base-diet" with or without
protein supplementation to avoid potential food selection bias that could confound the
results when using high- and low-protein diets.

Inclusion Criteria:

- Body mass index (BMI) between 30 and 50 kg/m2

- Subjects who are sedentary (<1.5 h of exercise/week)

- Subjects with a high habitual protein intake (>1.2 g/kg body mass/day)

Exclusion Criteria:

- Subjects with evidence of significant organ system dysfunction (e.g. diabetes, severe
cardiovascular disease, hyperlipidemia, cirrhosis, hypogonadism, uncontrolled hypo-
or hyperthyroidism; uncontrolled hypertension)

- Subjects with metal implants

- Individuals with cancer or cancer that has been in remission for <5 years,

- Individuals with dementia,

- Individuals who use tobacco products,

- Subjects who are taking medications known to affect glucose metabolism (e.g.,
steroids),

- Subjects taking medications to control certain medical conditions (e.g.,
hypertension) will be included if the drug regimen has been stable for at least 6
months before entering the study and is not expected to change during the study.

- Women who are pregnant due to changes in body composition and decreases in insulin
sensitivity caused by pregnancy