Abstract MP86: Hemodynamic and Metabolomic Change From Lifestyle Driven Weight Loss in Obese Adolescents

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Background: While bariatric surgery is known to induce hemodynamic and metabolic pathway alterations, lifestyle-driven weight loss in obese adolescents are not well characterized with respect to hemodynamic and metabolomic effects. We studied aortic function and urine metabolomics changes in obese adolescent volunteers attending weight loss summer camps.

Methods: Adolescents (n=45, 71% girls, mean age 15±1 year) attending long-standing weight loss camps over 3 summers volunteered to have weight, long term diet and activity history, and vascular tonometry after overnight fast at camp entry and exit. A subset (n=32) also gave urine entry and exit urine samples for metabolomic analysis (Metabolon, Durham NC). Camp administrators followed pre-existing protocols encouraging campers toward 5 hours or more of structured activity and free play as well as nutritionist-designed meal plan restricted to age-sex specific calorie goals. Paired students T-tests were used to assess changes in anthropometrics and hemodynamics. Osmolality-adjusted metabolomic changes were analyzed using principal components analysis; paired T-test with multiple comparison adjustment by Storey-Tibshirani false discovery rate thresholding; and Random Forest decision tree ensembles with selection of the top 30 biochemicals in variable importance gleaned from the Mean Decrease Accuracy metric, which randomly permutes a given chemical and reassesses predictive accuracy throughout the tree ensembles, and then grouped into pathway categories.

Results: Median camp length was 6 weeks (25%,75% IQR 5,7). Campers on average lost body 11±4% of body weight (99±20 to 88±17 kilograms, p<0.0001). Supine systolic blood pressure declined from 115±11 to 111±12 mmHg (p<0.01), diastolic blood pressure from 57±8 to 52±7 mmHg (p<0.0001), and heart rate from 73±10 to 62±11 beats per minute (p<0.0001). Carotid femoral pulse wave velocity decreased from 5.4±0.7 to 5.1±0.6 meters per second (p<0.0001). This change in arterial stiffness was not dependent on changes in heart rate nor distending pressure. Augmentation index did not significantly change from 17±11% to 16±9% (p=0.5). On urine metabolomic analysis, altered biochemical pathways included lipid metabolism, bile acids, and carbohydrate excretion.

Conclusions: Diet and activity driven weight loss in excess weight adolescents is associated with salutary hemodynamic improvement and specific metabolic alterations, paralleling findings after bariatric surgery. More investigation into the mechanisms of lifestyle driven weight loss is warranted.

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