Time-Restricted Feeding

We propose to conduct a randomized 6-day isocaloric crossover feeding study in humans with prediabetes and obesity. We will study the effect of restricting the timing of caloric intake to earlier in the day (TRF) versus later in the day (usual feeding pattern, UFP) on glycemia and inflammation in an inpatient setting.

Time Restricted Feeding (TRF) is a variant of intermittent fasting that confines caloric intake to active daytime hours and involves fasting for 12 to 14 hours. Circadian misalignment caused by changes in sleeping and eating behaviors has emerged as having a detrimental impact on weight, glucose homeostasis and other cardiovascular disease-related outcomes. Feeding during active periods appears to be advantageous for weight, glucose metabolism and lipid profiles whereas feeding during the inactive period confers deleterious effects on these outcomes. Therefore, TRF shows great promise as a novel intervention for addressing obesity and related cardiovascular outcomes.

Animal studies suggest that timing of feeding, including intermittent fasting or TRF, decreases inflammation and causes ketosis. Human studies that examined time restricted feeding for improvement in glycemia in as little as 4 days did not observe changes in clinical markers of inflammarion such as hsCRP. Moreover, systemic and adipose tissue inflammation as it occurs in obesity shows dynamic changes in the context of weight loss that would not be clearly apparent in a weight stable state. A potential mechanistic link between glycemic improvement and systemic inflammation would be the Receptor for Advanced Glycation End-Products (RAGE) and its soluble form (sRAGE).This form of inflammation has not been measured in reported eTRF studies and its relationship with eTRFwould bea significant contribution from the proposed study.

Eligibility Criteria:
Inclusion Criteria:

1. BMI \>25 kg/m2
2. If taking probiotics during screening, must agree to continue taking them at the same dosage and frequency
3. HbA1C 5.7-6.4%
4. Willing to eat only the food provided
5. Willing to follow the feeding schedule, including fasting for 14 hours/day for 7 days
6. Willing to remain on the RU inpatient 24/7 unit except for weekend passes
7. Normally sleep between the hours of 10 pm and 8 am
8. Weight stable over the last 3 months defined as no more than a 5% change

Exclusion Criteria:

1. Diabetes
2. Any intermittent feeding diet within the last 2 weeks
3. HIV positive
4. Hepatitis
5. Self-reported autoimmune diseases (rheumatoid arthritis, SLE (lupus), Crohn's
6. Disease, psoriasis, etc.)
7. Current use of metformin
8. Smoked tobacco within the last 8 weeks
9. Taking any weight loss medication
10. Current use of systemic steroids
11. Allergic to adhesive tape
12. Taking clinically useful medications that contribute to significant weight loss or weight gain ie tricyclic antidepressants, some SSRIs, lithium, antipsychotics, some anticonvulsants, steroids, beta blockers, some antihistamines.
13. Currently pregnant
14. Any medical, psychological or social condition that, in the opinion of the Investigator, would jeopardize the health or well-being of the participant during any study procedures or the integrity of the data