Exercise After Clinically Significant Weight Loss

Weight will measured in a hospital gown on a balance beam scale. Change in weight will be calculated as the participant weight change from the end of the weight loss phase to the end of the weight maintenance phase (week 28 weight subtracted from the week 10 weight). A positive value indicates an increase in weight and a negative value indicates a reduction in weight

Fitness will be measured using a modified Balke protocol on a treadmill. Participants will walk at an initial speed of 2.0 mph with 0% grade for the first 3 minutes after which the treadmill speed will increase to 3.0 mph for the next 3 minutes. The treadmill grade will be increased by 2.5% every 3 minutes until volitional exhaustion. Respiratory gases (VO2, CO2) and ventilation will be measured continuously using a True Max 2400 Metabolic Measurement Cart. Change in fitness will be quantified as the value at follow-up (week 28) subtracted from the value at week 10. An increase value will indicate an increase in fitness, while a decrease in the value will indicate a reduction in fitness

Dual-energy X-ray absorptiometry will be used to measure changes in fat mass and lean mass. Body fat will be quantified as the percent of fat relative to the total body mass. Lean mass will be quantified as the percent of lean tissue relative to the total body composition. This will be calculated at week 10 and at week 28. Change in these variables will be quantified as by subtracting the week 10 value from the week 28 value. Thus, a change in positive direction is associated with an increase in body fat or lean mass and a negative value represents a decrease.

Waist circumference will be measured at the natural waist (midway between the inferior border of the rib cage and the superior aspect of the iliac crest) with a gulick tape measure. Both landmarks (the inferior border of the ribcage and the superior aspect of the iliac crest) will be marked and the distance will be measured to determine the appropriate measurement site. Staff will confirm that: 1) the measurement tape remains horizontal; 2) the tape touches the entire circumference of the participant; 3) abdominal tissue is not compressed; 3) the tape measure is not within abdominal folds; 4) the measurement is taken at the end of normal respiration. The measurement will be repeated an additional time, and the reported value will be the average of these measurements. Both measurements must be within 0.5 cm to be considered acceptable for data purposes. The change in waist circumference will be quantified as the the week 28 value subtracted from the week 10 value.

A fasting blood sample will be used to measure low density lipoprotein, high density lipoprotein, total cholesterol, and triglycerides will be measured. It will be quantified as the specific amount of the lipoprotein within the blood in mg/dL for all lipid variables. Participants will be fasted at least 12 hours prior to the blood draw. Change will be quantified as the week 28 value subtracted from the week 10 value. A positive value indicates an increase in the blood lipid variable and a negative value is associated with a reduction in the variable.

Brachial and aortic blood pressure will be measured using a sphygmocor XCEL. Blood pressure is quantified in mmHg and will be taken in the seated position after a 5 minute rest. Change in blood pressure is quantified by subtracting the week 28 value from the week 10 value. Thus, a positive number is associated with an increase in blood pressure across the time point and a decrease indicates a decrease in blood pressure

Change in fasting glucose level. Fasting glucose level refers to the concentration of glucose within the blood (mg/dL). The change in fasting glucose level is quantified by subtracting the week 28 value from the week 10 value. Thus, a positive value indicates an increase in glucose level and a negative value indicates a decrease in glucose.

Fasting insulin represents the concentration of insulin in the blood. A positive value represents an increase in insulin concentration and a negative value represents a decrease in insulin concentration.

High sensitivity c-reactive protein is a marker of systemic inflammation and is quantified in mg/L. A postive value indicates an increase in c-reactive protein and a negative value represents a decrease in c-reactive protein.

Resting metabolic rate (RMR) was measured in a quiet, temperature-controlled room using indirect calorimetry (TrueOne 2400, Parvo Medics, Salt Lake City, UT) with a clear ventilated canopy and dilution pump. Initially, participants rested in the seated position for 20 minutes. Participants then rested in the supine position in the dimly lit room for at least 20 additional minutes with the hood covering their head. RMR was determined from approximately 10 minutes of data at the end of the procedure when the FECO2 dilution was steadily maintained in the range of 1.0 and 1.2%. RMR data was considered valid when the coefficient of variations for resting energy expenditure, VO2 and VCO2, were ≤10% RMR will be expressed as the estimated amount of calories needed for a given a day (kcals/day). Change in RMR will be quantified as the week 28 value subtracted by the week 10 value. An increase in the value reflects an increase in RMR and a negative value represent a decrease.

Insulin sensitivity will be measured using an oral glucose tolerance test. With the results of the oral glucose tolerance test at baseline, insulin sensitivity was calculated with the Matsuda index. Insulin sensitivity was calculated with Matsuda index: [10,000 / √glucose minute 0 x insulin minute 0) (mean glucose (OGTT) x mean insulin OGTT)]. A higher result is better.

This measure describes the average size of the low density lipoprotein particles and high density lipoprotein participles

Arterial stiffness will be measured using pulse wave velocity. Participants will refrain from large meals and caffeine for at least 2 hours and alcohol, vigorous exercise and vasoactive medication for at least 12 hours. Testing will occur in a quiet temperature controlled room. Carotid to femoral pulse wave velocity (PWV) and aortic blood pressure parameters will be measured using a SphygmoCor XCEL (Itasca, IL). PWV will be obtained in the supine position after a 15-minute rest. Investigators will measure the speed of the pulse from the carotid (artery in neck) to the femoral artery (artery in the leg). PWV parameters will be obtained in duplicate in concert with current guidelines and will be quantified in m/sec.

Participants will wear an ActivPal accelerometer for seven consecutive days, 24-hrs/day. The amount of time spent sitting and standing and steps will be calculated

Quality of life (QOL) will be measured by the short form health survey (SF-36). SF36 consists of 36 questions that measure patient's HRQoL in 8 domains: physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH) that represent the physical HRQoL, vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH) that represent the mental HRQoL. Each domain is scored from 0 (worst health status) to 100 (best health status).

The SF-36 also produces a measure of overall physical health (physical component score [PCS]) and overall mental health (mental component score [MCS]). Scoring of these items are standardized using means and standard deviations from the general US population. Aggregate PCS and MCS scores are standardized using a linear T-Score transformation to have a mean of 50 and a standard deviation of 10.

Food Frequency Questionnaire (FFQ) contains approximately 105 items grouped by categories and is completed for both frequency of consumption as well as portion size selections by the individual. The questionnaire, upon completion, provides estimated daily intake values for selected nutrients (kilocalories, macronutrients, and micronutrients) and provides information on food group servings.

The participants are weighed on scale in a hospital gown

Fitness will be measured using a modified Balke protocol on a treadmill. Participants will walk at an initial speed of 2.0 mph with 0% grade for the first 3 minutes after which the treadmill speed will increase to 3.0 mph for the next 3 minutes. The treadmill grade will be increased by 2.5% every 3 minutes until volitional exhaustion. Respiratory gases (VO2, CO2) and ventilation will be measured continuously using a True Max 2400 Metabolic Measurement Cart. Change in fitness will be quantified as the value at follow-up (week 28) subtracted from the value at week 10. An increase value will indicate an increase in fitness, while a decrease in the value will indicate a reduction in fitness

Dual-energy X-ray absorptiometry will be used to measure changes in fat mass and lean mass. Body fat will be quantified as the percent of fat relative to the total body composition. Lean mass will be quantified as the percent of lean tissue relative to the total body composition. Change in these variables will be quantified as by subtracting the week 10 value from the week 28 value. Thus, a change in positive direction is associated with an increase in body fat or lean mass and a negative value represent a decrease.

Waist circumference will be measured at the natural waist (midway between the inferior border of the rib cage and the superior aspect of the iliac crest) with a gulick tape measure. Both landmarks (the inferior border of the ribcage and the superior aspect of the iliac crest) will be marked and the distance will be measured to determine the appropriate measurement site. Staff will confirm that: 1) the measurement tape remains horizontal; 2) the tape touches the entire circumference of the participant; 3) abdominal tissue is not compressed; 3) the tape measure is not within abdominal folds; 4) the measurement is taken at the end of normal respiration. The measurement will be repeated an additional time, and the reported value will be the average of these measurements. Both measurements must be within 0.5 cm to be considered acceptable for data purposes. The change in waist circumference will be quantified as the the week 28 value subtracted from the week 10 value.

A fasting blood sample will be used to measure low density lipoprotein, high density lipoprotein, total cholesterol, and triglycerides will be measured. It will be quantified as the specific amount of the lipoprotein within the blood in mg/dL for all lipid variables. Participants will be fasted at least 12 hours prior to the blood draw. Change will be quantified as the week 10 value subtracted from the week baseline value

Brachial and aortic blood pressure will be measured using a sphygmocor XCEL. Blood pressure is quantified in mmHg and will be taken in the seated position after a 5 minute rest. Change in blood pressure is quantified by subtracting the week 10 value from the baseline value. Thus, a positive number is associated with an increase in blood pressure across the time point and a decrease indicates a decrease in blood pressure

Change in fasting glucose level. Fasting glucose level refers to the concentration of glucose within the blood (mg/dL). The change in fasting glucose level is quantified by subtracting the week 10 value from the baseline value. Thus, a positive value indicates an increase in glucose level and a negative value indicates a decrease in glucose.

Fasting insulin represents the concentration of insulin in the blood. A positive value represents an increase in insulin concentration and a negative value represents a decrease in insulin concentration.

High sensitivity c-reactive protein is a marker of systemic inflammation and is quantified in mg/L. A positive value indicates an increase in c-reactive protein and a negative value represents a decrease in c-reactive protein.

Resting metabolic rate (RMR) was measured in a quiet, temperature-controlled room using indirect calorimetry (TrueOne 2400, Parvo Medics, Salt Lake City, UT) with a clear ventilated canopy and dilution pump. Initially, participants rested in the seated position for 20 minutes. Participants then rested in the supine position in the dimly lit room for at least 20 additional minutes with the hood covering their head. RMR was determined from approximately 10 minutes of data at the end of the procedure when the FECO2 dilution was steadily maintained in the range of 1.0 and 1.2%. RMR data was considered valid when the coefficient of variations for resting energy expenditure, VO2 and VCO2, were ≤10% RMR will be expressed as the estimated amount of calories needed for a given a day (kcals/day). Change in RMR will be quantified as the week 10 value subtracted by the baseline. An increase in the value reflects an increase in RMR and a negative value represent a decrease.

Insulin sensitivity will be measured using an oral glucose tolerance test. With the results of the oral glucose tolerance test at baseline, insulin sensitivity was calculated with the Matsuda index.

Insulin sensitivity was calculated with Matsuda index: [10,000 / √glucose minute 0 x insulin minute 0) (mean glucose (OGTT) x mean insulin OGTT)]. A higher result is better.

Central Arterial stiffness will be measured using a SphygmoCor XCEL (Itasca, IL). Participants will refrain from large meals and caffeine for at least 2 hours and alcohol, vigorous exercise and vasoactive medication for at least 12 hours. Testing will occur in a quiet temperature controlled room in the seated position after a 5 minute rest. Augmentation index represent central arterial stiffness and will be quantified via augmentation index (%). The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. A lower value indicates better stiffness

Participants will wear an ActivPal accelerometer for seven consecutive days, 24-hrs/day. The amount of time spent sitting and standing and steps will be calculated

Quality of life (QOL) will be measured by the short form health survey (SF-36). SF36 consists of 36 questions that measure patient's HRQoL in 8 domains: physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH) that represent the physical HRQoL, vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH) that represent the mental HRQoL. Each domain is scored from 0 (worst health status) to 100 (best health status).

The SF-36 also produces a measure of overall physical health (physical component score [PCS]) and overall mental health (mental component score [MCS]). Scoring of these items are standardized using means and standard deviations from the general US population. Aggregate PCS and MCS scores are standardized using a linear T-Score transformation to have a mean of 50 and a standard deviation of 10.

Food Frequency Questionnaire (FFQ) contains approximately 105 items grouped by categories and is completed for both frequency of consumption as well as portion size selections by the individual. The questionnaire, upon completion, provides estimated daily intake values for selected nutrients (kilocalories, macronutrients, and micronutrients) and provides information on food group servings.

LDL particle Size. This measure describes the average size of the Low density lipoprotein particles