Effect of Hypoglycemia on Sleep
Condition: Hypoglycemia
MeSH terms: Hypoglycemia
Study type: Interventional

Summary: 
      Growing evidence provided by many observational studies has established a strong link between
      decreased sleep duration and poor glucoregulation. Sleep deprivation and poor sleep quality
      induce insulin resistance and decrease glucose tolerance in healthy individuals. However, the
      influence of poor sleep quality on glycemic control of patients with Type 1 diabetes mellitus
      (T1DM) is unknown. Persistent sleep deprivation among patients with T1DM has been reported,
      and this sleep loss can be attributed in part to nocturnal hypoglycemia. Nocturnal iatrogenic
      hypoglycemia is a limitation of current intensive insulin therapies. Although severe
      hypoglycemia is associated with adverse events such as seizures and death, less severe
      nocturnal hypoglycemia has been linked to broad range of adverse consequences, both acutely
      and long term. Hypoglycemia stimulates the sympathetic nervous system as a stress response,
      leading to the stimulation of the hypothalamic-pituitary-adrenal axis (HPA). This results in
      a counter regulatory hormone cascade, which elicits an excessive cortisol secretion, which is
      known to cause sleep disturbance and could impair glucose homeostasis after the hypoglycemic
      event. The hyperinsulinemia in T1DM patients promotes HPA hyperactivity as well, which is
      also associated with impaired sleep quality by leading to sleep fragmentation, decreased slow
      wave sleep and shortened sleep duration. Sleep disturbances due to nocturnal hypoglycemia can
      exacerbate HPA axis dysfunction, adversely affecting the sleep-wake cycle.

      The goal of the study is to understand the impact of nocturnal hypoglycemia on sleep.
    

Detailed description: 
      The study duration is 4 weeks long, during which subjects will undergo a 1 week run-in period
      followed by 3 randomized weeks of observational study. During the 1 week run-in period,
      subjects will familiarize themselves with the CGM and the other data collection procedures.
      Following the run-in week, the subject will be randomized to a specific order of observation
      weeks. The three observation weeks are a resistance training week, an aerobic exercise week
      and a control week with no explicit exercise. During the observation weeks, there will be 4
      interventions planned, two during both the aerobic exercise and the resistance training week.
      See Schematic below for details. During both the aerobic exercise week intervention visits,
      subjects will exercise for ~45 minutes on a treadmill and during the resistance training
      week, subjects will perform strength training exercises for 1-3 sets per exercise at a weight
      that can be lifted for 8-12 repetitions (~60-80% of 1-repetition max). The duration of the
      resistance training period is expected to be ~45min. Subjects will continue to perform daily
      activities during each of the weeks.

      During each week, the subject will wear one subcutaneous DexcomTM G4 or DexcomTM G4 Share
      continuous glucose monitoring (CGM) system, one activity monitor- ActiGraph wGT3X-BT or
      ActiGraph GT9X, one insulin pump (subject's own pump) and one Samsung Galaxy S4 phone loaded
      with two applications- meal memory and moves. The CGM system will provide sensed glucose data
      every 5 minutes. The CGM data will be blinded to the patient to prevent any abrupt changes in
      behavior. The accuracy of the sensed data will be obtained by reference measurements of
      capillary blood glucose. The activity monitor will be secured on the dominant wrist and uses
      an accelerometer to collect movement data at a high frequency (80Hz). The activity monitor
      measures both motion and ambient light, this data would be used to determine the various
      sleep quality measures. The subject's insulin dosage information from the pump will be
      downloaded for data analysis purposes. The subject's daily meal intake (photographic log and
      note diary) and daily movement pattern information will be downloaded from the phone. During
      the 4 exercise intervention visits, subject's heart rate, accelerometry information from the
      torso and oxygen consumption measured breath by breath may be collected for data analysis
      purposes.
    

Intervention name(s): Aerobic Exercise; Resistance Exercise
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Subjects will exercise on a treadmill for 45 minutes twice during the intervention week. Subjects will exercise at a fixed intensity level to a target heart rate (±10%) based on the heart rate achieved at 60% of their VO2max determined at screening. The speed and grade of the treadmill will be adjusted by trained research personnel with a goal of keeping participants within their target heart rate range for the entire 45 minutes.; Subjects will participate in resistance exercises for 45 minutes twice during the intervention week. Subjects will perform multiple-joint exercises with slow to moderate lifting velocity, for 1-3 sets per exercise at a weight that can be lifted for 8-12 repetitions (~60-80% of 1-repetition max). The exercises may include leg press, bench press, leg extension, leg flexion and seated row. Subjects will perform the exercises through the full range of motion. Between each set of repetitions, there would be a 2 minute rest period. The duration of the exercise testing would be approximately 45 minutes.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Sleep; Exercise