How Quickly Can the Effects of Excessive Caloric Intake on Insulin Resistance be Reversed?

Temple University

Status: Active, not recruiting

Conditions: Obesity

Treatments: Other: reduced caloric intake; Other: high caloric intake

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02505958

22331

R01DK090588 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Objective: To show that a 1-2 day reduction of caloric intake can reduce the insulin resistance produced by several days of overnutrition. Approach: Healthy volunteers will be admitted to the Clinical Research Center and undergo a baseline euglycemic-hyperinsulinemic clamp study to assess their insulin resistance. Subjects will then start on an overnutrition program for 4 days consisting of 3 meals and 3 snacks containing ~6,000 Kcal/24hours. A second clamp study will be performed on day 5 to demonstrate the overnutrition induced increase in insulin resistance. Starting on day 5 the subject's caloric intake will be reduced to ~1,000 Kcal for 2 days (day 5 and 6). After that on the morning of day 7, a third hyperinsulinemic-euglycemic clamp will be performed to determine whether the reduced caloric intake did reduce insulin resistance and the volunteer will be discharged from the Clinical Research Center.

Full description

Study volunteers will be admitted to the Clinical Research Center at Temple University Hospital. After an overnight fast, body composition will be determined non-invasively by bioimpedance analysis (4) and a 4 h euglycemic-hyperinsulinemic clamp (using only FDA-approved regular insulin) as previously described (5) will be performed during which serum samples will be obtained for measurement of glucose, insulin, free fatty acids, ketone bodies and lipids. Oxidative stress ( 6) will be measured by 24 hour urine collections (analyzed for isoprostane content via 8-isoprostaglandin-F2alpha throughout the study period. Respiratory gas exchange rates (7) will be determined at hourly intervals (with a metabolic cart (True One, Parvo Utah) during the clamp studies and once a day on Days 2 through 6. After that, (at about 1:00 in the afternoon on Day 1) the volunteers will be started on a diet program for 4 ½ days, consisting of 3 meals and 3 snacks over a 24 hour period and containing ~ 6000 Kcal/24 h. The main meals (containing ~ 1500 Kcal/meal) will be served at ~ 8:00 in the morning (breakfast), 1:00 in the afternoon (lunch) and approximately 7:00 in the evening (dinner), the snacks (~ 500 Kcal/each) at approximately 11:00 in the morning, 4:00 in the afternoon and 11:00 in the night. On days 5 and 6, volunteers will receive 3 meals, each will contain ~333 calories. Each morning blood samples will be obtained to measure glucose insulin, free fatty acids and ketone bodies. Daily 24 h urine collections will be obtained each day. In the morning of Days 5 and 7, all procedures described for Day 1 will be repeated. In the afternoon of Day 7, the volunteers will be discharged from the hospital.

Enrollment: 1 patient

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: Healthy non-obese men and women -

Exclusion Criteria: Subjects with diabetes or a history of obesity surgery or with more than modest health problems

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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1 participants in 2 patient groups

high caloric intake

Other group

Description:

Volunteers will receive 3 meals and 3 snacks over a 24 hour period which will contain \~ 6,000 calories. Main meals will consist of \~ 1,500 calories and snacks will contain \~ 500 calories.

Treatment:

Other: high caloric intake

reduced caloric intake

Other group

Description:

On days 5 and 6 subjects will receive 3 meals only and each meal will contain \~ 333 calories for a total of 1,000/ 24 hours.

Treatment:

Other: reduced caloric intake