Dinner Time for Obesity and Prediabetes

Obesity and its metabolic complications are leading causes of global morbidity and mortality. Evidence is mounting that inappropriate timing of food intake contributes to obesity. Specifically, late eating is associated with greater weight gain and metabolic syndrome. However, the mechanism by which late eating harms metabolism is not fully understood but may be related to mis-timing of food intake in relation to the body's endogenous circadian rhythm. Conversely, harmonization of eating timing with endogenous circadian rhythm may optimize metabolic health. In this study the investigators will use gold-standard methods of characterizing circadian rhythm in humans to examine the metabolic impacts food timing relative to endogenous circadian rhythm.

This is a randomized, cross-over study that examines the metabolic impact of early vs late dinner, as defined by proximity of food intake to an individual's biological night as determined by dim light melatonin onset (DLMO) in normal-weight, healthy adult volunteers and in adults with obesity and prediabetes. Each participant will first undergo circadian phenotyping at the Johns Hopkins Bayview Clinical Research Unit (Baltimore, Maryland), with assessment of DLMO and core body temperature profile, as well as wrist actigraphy. Thereafter, participants will be crossover randomized to (1) a 24-hour metabolic chamber protocol where dinner is eaten 3 hours before DLMO (early dinner), or (2) a 24-hour metabolic chamber protocol where dinner is 1 hour eaten after DLMO (late dinner), both to be performed at the NIH Metabolic Clinical Research Unit (Bethesda, Maryland). The timing and nutritional contents of all meals, as well as sleep timing and duration, will be held constant. Oral \[2H31\] palmitate will be given with each dinner condition to quantify dietary fat oxidation. The 2 dinner conditions will occur in random order, with a 3- to 4-week washout period.

The investigators are enrolling both Normal-Weight Healthy (NWH) and Obesity-Prediabetes (OPD) research participants. At this time (5/2023) the investigators are focusing on the NWH group.

Eligibility Criteria:
The investigators are enrolling both Normal-Weight Healthy (NWH) and Obesity-Prediabetes (OPD) research participants. At this time (5/2023) the investigators are focusing on the NWH group.

Inclusion Criteria:

* For the Normal-Weight Healthy (NWH) cohort: Healthy male and female adults, age 18-50, with BMI 18-24.9 kg/m2 inclusively
* For the Obesity-Prediabetes (OPD) cohort: Male and female adults, age 18-50, with BMI ≥30 kg/m2 and prediabetes
* All participants must be able to understand study procedures, to comply with the procedures for the entire length of the study and be fully mobile.

Exclusion Criteria:

* Sleep disorder including insomnia, untreated moderate-severe sleep apnea, restless leg syndrome, or narcolepsy
* Night shift work
* Extreme delayed sleep phase defined as self-reported routine bedtime later than 1:00 AM or having mid-sleep on free days later than 5:00 AM on the Munich Chronotype Questionnaire (MCTQ) or DLMO later than 24:00
* Gastroesophageal reflux disease that affects ability to tolerate a dinner close to bedtime
* Active smoking
* Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
* Diabetes (type 1 or 2) or on any diabetes medications besides metformin
* Evidence of metabolic or cardiovascular disease, or disease that may influence metabolism (e.g. cancer, thyroid disease)
* Hemoglobin A1c ≥5.7% for NWH cohort; Hemoglobin A1c ≥6.5% for OPD cohort
* Hemoglobin \< 10 g/dL
* Self-reported kidney disease
* Any known history of an inherited metabolic disorder
* Pregnant or lactating female (pregnancy test will be required prior to metabolic visits)
* Peri-menopausal or post-menopausal female as determined by follicle stimulating hormone of \> 30 mIU/mL or fewer than 3 menstrual periods in 6 months
* Professional or collegiate athlete
* Participants who have travelled across time zones must have adequate time to recover from jet lag prior to enrollment (i.e., at least 3 days per time zone). Travel across \>1 time zone after enrollment in the study will not be permitted.
* Weight less than 40 kg or more than 180 kg
* Gastrointestinal disorders that can lead to obstruction of the digestive tract (i.e. diverticular disease, history of bowel obstruction, inflammatory bowel disease, motility disorder)
* History of any surgical procedures in the gastrointestinal tract.
* Swallowing disorders
* Taking any prescription medication or other drug that may influence metabolism (e.g. diet/weight-loss medication, asthma medication, blood pressure medication, psychiatric medications, corticosteroids, or other medications at the discretion of the PI and/or study team)
* Chronic use of sedative hypnotics, anxiolytics, opiates
* Use of medications that can affect circadian rhythm (beta blockers, melatonin)
* Presence of a cardiac pacemaker or other implanted electro-medical devices
* Those who have to undergo strong electromagnetic field during the period of use of the ingestible thermosensor (i.e. MRI)
* Weight loss or gain of ≥ 5% of total body weight over the preceding 3 months
* Currently participating in a weight loss program
* Prior bariatric surgery
* Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, food allergies)
* History of significant intravenous access issues
* Non-English speaking individuals: The complexity of the instructions for various components of the study would make the study procedures difficult to follow in the setting of a language barrier.
* Other conditions or situations at the discretion of the PI