Behavioral Chronotype: Impact on Sleep and Metabolism

The timing of food intake and caloric distribution across the 24hr day are emerging as
contributing factors to weight gain. The idea that not only what you eat, but when you eat
can contribute to weight gain has garnered interest from both the scientific community and
the public. In fact, the distribution of caloric intake over the 24hr day has been recently
recognized as a potential source of "circadian misalignment" which can result in adverse
health outcomes, including overeating, impaired glucose tolerance, insulin sensitivity, and
cardiovascular disease risk. This study will provide proof-of-concept evidence on the impact
of misalignment on glucose metabolism and blood pressure regulation. This study will focus on
overweight individuals who are at high risk of obesity but are still on a trajectory that can
potentially be reversed by lifestyle changes. Following a careful assessment of the subject's
habitual sleep and meal timing and caloric distribution under real life conditions, a short
laboratory study will determine 24hr profiles of hormones involved in circadian timing, food
intake and cardiovascular risk in a session that will mimic habitual sleep/wake and caloric
distribution. Participants will then be randomized to one of three groups in which caloric
distribution across the day will either be equally distributed between 3 meals, or heavily
weighted to the morning or heavily weighted to the evening. During a 6-day semi-ambulatory in
patient intervention, combining laboratory and ambulatory procedures, study procedures will
assess the effect of experimentally changing caloric distribution across the day, advancing
versus delaying the dietary chronotype. After 7 days of this caloric distribution
intervention, we will then repeat the short laboratory session to assess whether the
intervention of caloric distribution altered any of the measured profiles. The outcome
measures will be the timing of the dim light melatonin onset (DLMO), blood pressure dipping,
and insulin sensitivity. The proposed work will provide unambiguous evidence related to the
efficacy of a novel lifestyle intervention - that could be more acceptable than dietary
restriction or exercise - to reduce the risk of T2DM and CVD in adults at risk due to age and
degree of adiposity. Moreover, our project will examine both middle-aged adults and older
adults. The younger age group is of interest because of a lesser burden of illness and of an
opportunity to alter the trajectory of aging at an earlier stage. The older age group is
expected to have more severe circadian disturbances at baseline, with the potential of a
larger effect on CM risk. The combined examination of metabolic risk and CVD risk in the
context of circadian function is also novel.

Inclusion Criteria:

- Healthy overweight and obese (25 kg/m2 ≤BMI< 40 kg/m2) men and women

- aged 30-75 years

- self-report sleeping at least 6.5-hrs/night but no more than 9-hrs/night, between
21:00 and 09:00

- signed informed consent

Exclusion Criteria:

- participation in a medically managed weight loss program within the past year

- undergone bariatric surgery

- dietary restrictions

- Subjects will not have undergone surgery, donated a unit of blood, worked night shifts
or crossed any time zones, or participated in another clinical study within a month
prior to the study.

- pregnancy in women

- lactating women

- Female subjects must not be actively going through menopause.

- prisoners

- inability to consent

- members of the study team

- Females with a hemoglobin < 11.5g/dL, and males with a hemoglobin < 13.5 g/dl will be
excluded from the study.

- presence of a sleep disorder such as moderate or severe sleep apnea (AHI≥15), a
Circadian Rhythm Sleep Disorder (DSM-V criteria for advance sleep phase syndrome,
delayed sleep phase syndrome, non 24-h sleep disorder, irregular sleep disorder and
shift-work related sleep disorder),

- a diagnosis of diabetes based on history or screening tests

- other forms of endocrine dysfunction including PCOS;

- a history of cognitive or other neurological disorders;

- a history of major psychiatric disorder based on DSM-V criteria,

- the presence of unstable or serious medical conditions,

- any GI disease that requires dietary adjustment;

- current, or use within the past month of melatonin, psychoactive, hypnotic, stimulant
or pain medications (except occasionally); beta blockers; habitual smoking (6 or more
cigarettes per week); caffeine consumption of greater than 500 mg per day