Clinical trial NCT02505958: How Quickly Can the Effects of Excessive Caloric Intake on Insulin Resistance be Reversed?
Official title: How Quickly Can the Effects of Excessive Caloric Intake on Insulin Resistance be Reversed?
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity
Keywords: insulin resistance, obesity, caloric intake
Lead sponsor: Temple University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2015-07-22
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.

Detailed 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.

Eligibility 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

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Primary outcomes:
measure: Changes in insulin resistance
timeFrame: baseline, day 4 and day 7
measure: Changes in oxidative stress
timeFrame: baseline, day1, day 2, day 3, day 4, day 5, day 6, day 7
measure: Changes in energy expenditure
timeFrame: baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7
measure: Changes in weight
timeFrame: baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7
measure: Changes in body composition
timeFrame: baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7
Secondary outcomes:
measure: Changes in blood glucose levels
timeFrame: baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7
measure: Changes in blood levels of insulin
timeFrame: Baseline, day1 day2, day 3, day 4, day 5, day 6, day 7
measure: Changes in blood levels of free fatty acids
timeFrame: Baseline, day1 , day 2, day 3, day 4, day 5, day 6, day 7
measure: Changes in blood ketone levels
timeFrame: baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7
measure: Changes in glucagon levels
timeFrame: baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
Study officials:
affiliation: Temple University
name: Ajaykumar Rao, MD
role: PRINCIPAL_INVESTIGATOR
References: