Sedentary Behavior and Health Outcomes Study

Rationale: Sedentary behavior (SB) can increase risk for type 2 diabetes. Interrupting SB is
a promising strategy to reduce risk, but the long-term success is not yet clear and data on
the relationship between in-lab and free-living metabolic responses are lacking. A better
understanding of the relationship between metabolic responses to sitting and interrupting
sitting in the lab and in a naturalistic environment will help us design effective and
targeted intervention strategies to prevent type 2 diabetes in youth.

Intervention: Participants (28 healthy weight and 28 overweight/obese youth; ages 11-15
years) from an ongoing longitudinal observational study (HS-12-00446) will complete: a) an
in-lab randomized crossover trial of acute metabolic responses to prolonged vs. SB
interruptions; and a subset (N=12) will complete b) two 4-day continuous glucose monitoring
(CGM) studies of effects of free-living habitual activity vs. SB interruptions on glucose
homeostasis.

Objectives/Purpose: The overall goal is to improve metabolic outcomes by interrupting SB in
youth with small bouts of exercise. The aim of this study is to investigate whether the
metabolic responses to interrupting sitting are the same in a controlled lab setting and a
free-living setting. This study will also try to explain why some children respond better to
these short interruptions in sitting than others by using three years of physical activity,
body fat, and weight trajectory data from an ongoing study (HS-12-00446).

Study Population: The study population will consist of participants currently enrolled in the
Mothers and Their Children's Health (MATCH) Study (PI: Dunton; HS-12-00446; ages 11-15
years).Eligible participants will have completed 3 years of semi-annual assessments of body
composition, physical activity, and dietary intake in the MATCH study.

Study Methodology: This study is a randomized crossover trial to compare the effectiveness of
interrupting SB on glucose homeostasis in the lab and free-living settings. All participants
(N=56) will complete one screening visit to determine eligibility, complete at fitness test,
and body composition analysis by bioelectrical impedance. After 7-21 days, all participants
will complete two 3-hour in-lab oral glucose tolerance tests (spaced 7-21 days apart). Prior
to the in-lab OGTT visits, participants will wear an activity monitor for 7 days on the right
thigh. The experimental conditions for the OGTTs will be: 1) 3-hour OGTT of continuous
sitting; and 2) 3-hour OGTT with sitting interrupted every 30 minutes with 3-minutes of
moderate intensity walking on a treadmill. There will be a 7-21 day washout period between
the OGTT visits. In addition, a subset of participants (N=12) who meet inclusion criteria and
who successfully complete both OGTT visits will complete a second randomized crossover trial
in the free-living environment. The experimental conditions for the free-living components
will be: 1) 4 days of habitual sedentary behaviors; and 2) 4 days of prompted short exercise
breaks during times in which sedentary behaviors have exceeded 30 minutes. Participants in
the free-living trial will wear an activity monitor and a continuous glucose monitor.

Study Arms: Participants will be assigned to receive in random order the continuous sitting
test at the first visit and the sitting interruptions test on the second visit, or vice
versa. The order of the free-living conditions will be the same as the in-lab condition
order.

Endpoints/Outcomes: The primary endpoints are: insulin, C-peptide, and glucose area under the
curve (AUC) in the in-lab experiments, and glucose AUC in the free-living experiments.

Follow-up: Study duration for those completing only the in-lab experiments is a minimum of 17
days and a maximum of 45 days to complete. For the subset of participants who are
additionally completing the free-living component, the study duration is a minimum of 25 days
and a maximum of 53 days.

Statistical Analyses: The populations for analyses include the full analytical dataset which
consists of all randomized study participants, with the exception of those participants in
the parent MATCH study who are not participating in this research study.

Inclusion Criteria:

1. current/past participant in the MATCH Study

2. good general health

3. fasting plasma glucose <100 mg/dL

4. BMI greater than the 5th percentile

Exclusion Criteria:

1. significant cardiac or pulmonary disease likely to or resulting in hypoxia or
decreased perfusion

2. evidence of impaired glucose tolerance or type 2 diabetes

3. presence of other endocrinologic disorders leading to obesity (e.g.: Cushing Syndrome)

4. current or past anti-psychotic drugs use that would affect metabolism

5. non-diet treatment for hypertension or dyslipidemia

6. precocious puberty and/or receiving androgen and estrogen therapy

7. medication use known to affect body composition/weight