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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02505958
• Other study ID #: 22331
• Secondary ID: R01DK090588
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 2014
• Est. completion date: December 31, 2023

Study information

• Verified date: July 2022
• Source: Temple University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

-

Related Conditions & MeSH terms

• Insulin Resistance
• Obesity

Intervention

Other:
• high caloric intake
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.
• reduced caloric intake
On days 5 and 6, volunteers will received 3 meals (~333 calories each) totaling ~ 1,000 calories/24 hours.

Locations

Country	Name	City	State
United States	Temple University Hospital	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Temple University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in insulin resistance	Insulin resistance will be determined by measuring changes in insulin-stimulated total body glucose uptake during euglycemic hyperinsulinemic clamping	baseline, day 4 and day 7
Primary	Changes in oxidative stress	24 hour urine collections analyzed for isoprostane content	baseline, day1, day 2, day 3, day 4, day 5, day 6, day 7
Primary	Changes in energy expenditure	Changes in energy expenditure will be assessed with a metabolic cart (indirect calorimetry)	baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7
Primary	Changes in weight	Subjects will be weighed daily	baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7
Primary	Changes in body composition	Body composition will be determined by bioelectric impedance analysis	baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7
Secondary	Changes in blood glucose levels	Daily blood samples will be analyzed to determine glucose levels of glucose.	baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7
Secondary	Changes in blood levels of insulin	Daily blood samples will be analyzed to determine insulin levels	Baseline, day1 day2, day 3, day 4, day 5, day 6, day 7
Secondary	Changes in blood levels of free fatty acids	Daily blood samples will be analyzed to determine free fatty acid levels	Baseline, day1 , day 2, day 3, day 4, day 5, day 6, day 7
Secondary	Changes in blood ketone levels	Daily blood samples will be analyzed to determine ketone levels	baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7
Secondary	Changes in glucagon levels	Daily blood samples will be analyzed to determine glucagon levels	baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7