Impact of Sleep and Meal Timing on Food Intake Regulation
Condition: Obesity; Diabetes Mellitus, Type II; Cardiovascular Disease
MeSH terms: Cardiovascular Diseases; Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      This study will test the hypothesis that a late sleep (Ls) and/or late meal (Lm) behavioral
      pattern, with equal sleep duration, will promote positive energy balance and insulin
      resistance (IR).
    

Detailed description: 
      Sleeping patterns affect aspects of metabolism that may impact obesity risk; our lab is
      interested in studying whether sleep patterns play a role in the development of obesity.
      Individuals with late bedtimes and late rise times tend to have greater food intake which
      includes more fast food and sugar-sweetened beverages, less fruits and vegetables [1], larger
      portions, and later eating times [2] than those with earlier bedtimes. This sleeping pattern
      is highly prevalent: ~15 million Americans work on shifts other than regular day hours [3]
      and others subject themselves to 'social jetlag' (time difference between the middle of the
      sleep episode [midpoint of sleep] on work days and non-work days, similar to travel across
      time zones) [4]. The shift in sleep and meal times associated with these lifestyles results
      in misalignment of sleep and eating behaviors with the circadian clocks. These clocks,
      located in the brain and organs throughout the body, regulate metabolism and behavior and are
      affected by sleep and feeding. Disruption of clock genes in individual organs may be in part
      responsible for metabolic dysregulation [5]. Altering the coordination of sleep and meal
      timing may affect food reward valuation (brain) and metabolism (peripheral organs) to promote
      obesity and IR, observed more frequently in shift workers. This is the focus of this
      randomized, crossover, controlled study of 4 phases:

        -  Normal sleep (Ns; 0000-0800 h), Normal meals (Nm=meals at 1, 5, 11, and 12.5 h after
           awakening)=Ns/Nm

        -  Normal sleep (Ns; 0000-0800 h), Late meals (Lm=meals at 4.5, 8.5, 14.5, and 16 h after
           awakening)=Ns/Lm

        -  Late sleep (Ls; 0330-1130 h), Normal meals (Nm=meals at 1, 5, 11, and 12.5 h after
           awakening)=Ls/Nm

        -  Late sleep (Ls; 0330-1130 h), Late meals (Lm=meals at 4.5, 8.5, 14.5, and 16 h after
           awakening)=Ls/Lm Aim 1: To determine whether Ls and/or Lm, in individuals with habitual
           normal sleep duration and timing, alters one or both sides of energy balance, i.e. food
           intake and energy expenditure (EE), relative to Ns and Nm.

        -  Hypothesis 1: (a) Ls and Lm will have independent and interactive effects on food intake
           and EE. Intake at an ad libitum test meal and during a 24 h period, measured after 3 d
           of each intervention, will be greater during Ls and Lm, and this will be enhanced when
           Ls and Lm are combined, compared to Ns and Nm. (b) Resting metabolic rate (RMR) will be
           lower during the Ls and Lm phases, and this will be further reduced when Ls and Lm are
           combined compared to the Ns and Nm phases (Ns/Nm<Ls/Nm≤Ns/Lm<Ls/Lm).

      Aim 2: To determine whether neuronal responses to food stimuli in brain regions related to
      reward value explain differences in food intake.

      • Hypothesis 2: (a) Increased brain activity in response to visual presentation of food
      stimuli, using functional magnetic resonance imaging (fMRI), will be seen in Ls and Lm
      compared to Ns and Nm in the insula and the orbitofrontal cortex. Enhanced neuronal activity
      in response to foods will be most pronounced in the Ls/Lm phase (Ns/Nm<Ls/Nm≤Ns/Lm<Ls/Lm).
      (b) Neuronal responses to food stimuli will be related to pre-test neuropeptide Y (NPY),
      hypocretin-1, and subsequent food intake.

      Exploratory Aim 3: To determine whether meal or sleep timing affect glucose homeostasis and
      appetite-regulating hormones.

      • Hypothesis 3: Ls and Lm will result in lower insulin sensitivity (frequently sampled i.v.
      glucose tolerance test [FSIVGTT] and meal tolerance test [MTT]) than Ns and Nm
      (Ns/Nm>Ls/Nm≥Ns/Lm>Ls/Lm). Sleep and meal timing will have independent and interactive
      effects on the 24-h pattern of hormones regulating food intake (lower leptin and
      glucagon-like peptide-1 [GLP-1]; higher ghrelin, NPY and hypocretin-1).
    

Intervention name(s): Normal Sleep/ Normal Meal; Normal Sleep/ Late Meal; Late Sleep/ Normal Meal; Late Sleep/ Late Meal
Intervention type(s): Behavioral; Behavioral; Behavioral; Behavioral
Intervention description(s): The subject will be inpatient for 5 days, and sleep between the hours of 0000-0800 h, with meals at 1, 5, 11, and 12.5 (snack) h after awakening every day for 5 days. On night 3, we will insert a catheter in the participant's arm to facilitate multiple blood sampling overnight and the next day. On d 4, a frequently sampled i.v. glucose tolerance test (FSIVGTT) will be performed. A MTT will be performed at the scheduled lunch. At 1 h before dinner, participants will undergo fMRI scanning to assess neuronal responses to food stimuli and to examine functional connectivity with reward circuitry. On d 5, participants will be allowed to determine their own food intake at the scheduled meal and snack times. Participants will be discharged upon awakening on day 6.; The subject will be inpatient for 5 days and sleep between the hours of 0000-0800 h,with controlled meals at 4.5, 8.5, 14.5, and 16 (snack) h after awakening. On night 3, we will insert a catheter in the participant's arm to facilitate multiple blood sampling overnight and the next day. On d 4, at the scheduled breakfast time, a frequently sampled i.v. glucose tolerance test (FSIVGTT) will be performed. A MTT will be performed at the scheduled lunch. At 1 h before dinner, participants will undergo fMRI scanning to assess neuronal responses to food stimuli and to examine functional connectivity with reward circuitry. On d 5, participants will be allowed to determine their own food intake at the scheduled meal and snack times. Participants will be discharged upon awakening on day 6.; The subject will be inpatient for 5 days, and sleep between the hours of 0330-1130 h, with controlled meals at 1, 5, 11, and 12.5 (snack) h after awakening. On night 3, we will insert a catheter in the participant's arm to facilitate multiple blood sampling overnight and the next day. On d 4, at the scheduled breakfast time, a frequently sampled i.v. glucose tolerance test (FSIVGTT) will be performed. A MTT will be performed at the scheduled lunch. At 1 h before dinner, participants will undergo fMRI scanning to assess neuronal responses to food stimuli and to examine functional connectivity with reward circuitry. On d 5, participants will be allowed to determine their own food intake at the scheduled meal and snack times. Participants will be discharged upon awakening on day 6.; The subject will be inpatient for 5 days, and sleep between the hours o 0330-1130 h, with controlled meals at 4.5, 8.5, 14.5, and 16 (snack) h after awakening. On night 3, we will insert a catheter in the participant's arm to facilitate multiple blood sampling overnight and the next day. On d 4, at the scheduled breakfast time, a frequently sampled i.v. glucose tolerance test (FSIVGTT) will be performed. A MTT will be performed at the scheduled lunch. At 1 h before dinner, participants will undergo fMRI scanning to assess neuronal responses to food stimuli and to examine functional connectivity with reward circuitry. On d 5, participants will be allowed to determine their own food intake at the scheduled meal and snack times. Participants will be discharged upon awakening on day 6.
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Obesity; Metabolic Disorders