Clinical trial NCT02004002: Protein Intake & Insulin Action
Official title: Dietary Protein Intake, Insulin Sensitivity and β-cell Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2013-12-06
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this proposal is to determine whether dietary protein restriction has beneficial effects on skeletal muscle insulin sensitivity and β-cell function in obese men and women.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Insulin sensitivity
timeFrame: up to 8 wk dietary intervention
measure: total β-cell sensitivity index (Φtotal)
timeFrame: Before and after the 8 wk dietary intervention
Secondary outcomes:
measure: Disposition index
timeFrame: Before and after the 8 wk dietary intervention
Other outcomes:
Locations:
city: St Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Gordon Smith, PhD
role: PRINCIPAL_INVESTIGATOR
References: