The Metabolic Effects of Intermittent Fasting

Study Overview
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Brief Summary
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Caloric restriction has beneficial metabolic effects in humans including weight loss and improvement in blood pressure and lipid levels. Intermittent fasting has emerged as a popular alternative to caloric restriction as it does not require daily adherence to a dietary protocol, but whether the benefits of fasting protocols are dependent on weight loss is not known. In this study, the investigators will explore the metabolic effects of fasting and evaluate whether these effects, including negative effects on bone metabolism, are independent of weight loss.

Official Title
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The Effects of Fasting on Reprogramming of Lipid Metabolism and Bone Metabolism

Conditions
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Normal and Overweight Individuals at High-risk of Diabetes

Intervention / Treatment
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* Behavioral: Fasting arm
* Behavioral: Weight maintenance
* Behavioral: Counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women, ages 25-45 years BMI of at least 21 kg/m2 and up to and including BMI of 29 kg/m2 Normal thyroid function Regular menses (women) At least one first-degree relative with type 2 diabetes (T2D) and/or history of gestational diabetes Exclusion Criteria: Any chronic diseases including hypertension and Type 2 diabetes mellitus Indication for lipid-lowering therapy in non-diabetics, using the more stringent AHA guideline cutoff (LDL>190 or an estimated 10-year ASCVD risk of >7.5%) Chronic medications, including oral contraceptive pills Pregnant and/or breastfeeding History of an eating disorder 25-OH vitamin D level < 20 ng/mL Active substance abuse, including alcohol Subjects with a prior history of intermittent fasting The study physician feels that the subject may not be able to safely complete the protocol or may place themselves at risk by undergoing the protocol

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, controlled study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fasting<br>Subjects will fast one-day per week for 12 weeks | Behavioral: Fasting arm<br>* Study participants will fast one day per week for 12 weeks<br>|
| Experimental: Fasting with weight maintenance<br>Subjects will fast one-day per week for 12 weeks and maintain body weight | Behavioral: Fasting arm<br>* Study participants will fast one day per week for 12 weeks<br>Behavioral: Weight maintenance<br>* Study participants will be counseled to maintain body weight<br>|
| Placebo Comparator: Counseling<br>Subjects will be counseled on optimal diet and activity recommendations to maintain/achieve a normal BMI (standard of care) | Behavioral: Counseling<br>* Study participants will be counseled on optimal diet and activity recommendations for maintaining/achieving a normal BMI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Triglyceride carbon content and degree of saturation | Change in triglyceride carbon content and degree of saturation (% variation explained by both carbon number and double bond number in a regression model) between Baseline and Final Intervention visits | Baseline, 3 months | 
| Trabecular bone microarchitecture | Change in trabecular bone volume fraction at the radius between Baseline and Final Intervention visits | Baseline, 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Change in insulin sensitivity as assessed by hyperinsulinemic-euglycemic clamp between Baseline and Final Intervention visits | Baseline, 3 months |