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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Other: high caloric intake; Other: reduced caloric intake

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Changes in weight	Subjects will be weighed daily	baseline, day 1, day 2, day 3, day 4, day 5, day 6, day 7
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Temple University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Ajaykumar Rao, MD, Temple University

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: July 21, 2015
• First Submitted That Met QC Criteria: July 21, 2015
• First Posted (Estimate): July 22, 2015

Study Record Updates

• Last Update Posted (Actual): July 28, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: insulin resistance, obesity, caloric intake
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: 22331; R01DK090588 (U.S. NIH Grant/Contract)