Iron and Insulin Resistance in Overweight and Obese Humans
Condition: Glucose Intolerance; Insulin Resistance; Iron Metabolism
MeSH terms: Overweight; Insulin Resistance; Glucose Intolerance
Study type: Interventional

Summary: 
      Determine the effects of reducing whole-body iron stores in overweight/obese subjects (via
      one-time blood donation) on adipose tissue iron content, factors regulating iron homeostasis
      and lipolytic rate in adipose tissue, as well as measures of adipose tissue and whole-body
      insulin resistance.

      After a screening visit to determine eligibility, subjects will undergo a battery of tests
      for the determination of primary outcome measures at baseline. They will then donate 1 unit
      (~500 mL) of blood (at a local blood donation center) and return for a follow-up testing 4
      weeks after blood donation. During the 4-week period between study trials, subjects will be
      required to maintain a stable body mass and not alter their dietary or physical activity
      habits.
    

Detailed description: 
      Screening:

      If a potential subject meets the eligibility criteria after completing the general
      pre-screening questionnaire, they will be contacted to set up an in-person screening visit
      where the comprehensive written informed consent will be obtained. This visit may occur
      either at the Michigan Clinical Research Unit (MCRU) or at the Substrate Metabolism
      Laboratory (SML). Subjects will complete health history, food frequency, and physical
      activity questionnaires. Subjects that meet eligibility requirements and provide written
      informed consent will have a finger-stick performed for the assessment of hemoglobin
      concentration. Women with hemoglobin < 13.0 g/dL and men with hemoglobin < 14.0 g/dL will be
      withdrawn from the study.

      Percent body fat will be measured using Dual Energy X-ray Absorptiometry [DEXA]. Women will
      provide a urine sample for a urine pregnancy test prior to the DEXA scan; if a subject has a
      positive pregnancy test prior to the DEXA scan, they will be withdrawn. The DEXA body
      composition assessment test may be performed at the screening visit or scheduled anytime
      between the screening visit and the baseline trial.

      Baseline Trial:

      Subjects will be provided general instructions on what to eat in the 3 days leading up to
      their baseline trial and be required to abstain from planned exercise in the 3 days leading
      up to the baseline and post-blood donation study trials. They will record their dietary
      intake during the 3 days leading up to the baseline trial and replicate it during the 3 days
      prior to the post-blood donation study trial. They will be required to fast the night before
      the trials starting at 9:00PM.

      Subjects will arrive at MCRU at ~07:00AM. After measurement of body weight and resting blood
      pressure, intravenous catheters (IV) will be placed in each arm (one for blood sampling and
      the other for infusion).

      At ~7:50 AM blood samples (in 5 minute intervals) will be collected. A ~8:00 AM a
      tracer-labeled glycerol infusion will begin. The tracer-labeled glycerol infusion that is
      infused occurs naturally in the body. By injecting a slightly greater amount of this
      substance than is already in the body, the rate of fat breakdown and fat burning is able to
      be measured. One of the subject's hands will be placed within a "hot-hand box" to enable the
      study team to collect arterialized venous blood samples from the intravenous catheter. At
      ~08:30AM, a small sample of abdominal fat tissue will be collected. Between ~09:50 and 10:00,
      three blood samples will be collected to determine basal lipolysis. At ~10:00, we will start
      the hyperinsulinemic, euglycemic clamp procedure to measure the body's sensitivity to
      insulin. During this procedure insulin and glucose will be infused through the IV in the
      forearm and blood samples will be collected periodically to monitor the subjects blood sugar.
      The infusion rate of glucose will be changed accordingly to ensure that the subjects blood
      sugar is maintained at a healthy/normal level. This procedure will take about two hours.
      Following completion, The insulin will be discontinued and the subject will be provided a
      lunch and the glucose will be gradually tapered off over the next hour. The study team will
      ensure the subjects blood glucose levels are stable prior to discharge.

      Blood Donation:

      Subjects will donate blood within ~1 month after their baseline trial. Subjects will report
      to the Substrate Metabolism Laboratory between 24 and 72 hours following blood donation. A
      finger-stick will be performed for the measurement of hemoglobin concentration.

      Post-Blood Donation Trial:

      The exact same procedures as performed in the Baseline Trial will be repeated 4 weeks after
      the subject's blood donation.

      Diet/Physical Activity/Weight Maintenance:

      Subjects will be required to maintain their normal diet and physical activity habits during
      the study. Following the baseline trial, subjects will be provided with a scale and asked to
      weigh themselves at home on a daily basis. If body weight changes ±2kg from their initial
      weight, subjects will consult with our research dietitian for strategies to maintain weight
      during the period between study trials.
    

Intervention name(s): Blood Donation
Intervention type(s): Procedure
Intervention description(s): Subjects will donate blood within ~1 month after their baseline clinical trial. Subjects will report to the Substrate Metabolism Laboratory between 24 and 72 hours following blood donation. A finger-stick will be performed for the measurement of hemoglobin concentration.
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Basic Science