Context Amino acids (AAs) and their metabolites are altered with obesity and may be predictive of future diabetes in adults, but there are fewer studies on AAs, as well as conflicting findings on how they vary with obesity, in adolescents. Objective To determine whether plasma AAs vary with body composition and insulin sensitivity and are altered in response to exercise training. Design Cross-sectional, and an exercise intervention. Setting Tribal wellness center. Participants American Indian boys and girls, 11 to 17 years of age with obesity (Ob, n = 58) or normal weight (NW, n = 36). Intervention The Ob group completed 16 weeks of aerobic exercise training. Main Outcome Measure A panel of 42 plasma AAs. Results Compared with the NW group, the Ob group had lower aerobic fitness and insulin sensitivity (interactive homeostasis model assessment 2), 17 AAs that were higher, and 7 AAs that were lower. Branched-chain AAs (+10% to 16%), aromatic AAs (+15% to 32%), and glutamate were among the higher AAs; all were positively correlated with body fat and negatively correlated with insulin sensitivity. The lysine metabolite 2-aminoadipic acid (2-AAA) and the valine metabolite β-aminoisobutyric acid (BAIBA) were 47% higher and 29% lower, respectively, in the Ob group, and were positively (2-AAA) and negatively (BAIBA) correlated with insulin sensitivity. Exercise training increased aerobic fitness by 10%, but body composition, insulin sensitivity, and AAs were not significantly changed. Conclusions Several plasma AAs are altered in American Indian adolescents with obesity and are associated with insulin sensitivity, but they were not altered with this exercise intervention.

American Indians (AI) have high prevalence of diabetes in youth and may benefit from increasing physical activity as a strategy to improve metabolic health. We tested whether financial incentives would elicit greater frequency and/or duration of exercise in AI youth at high risk for developing diabetes. Overweight/obese AI boys and girls, 11–20 years old, were instructed to exercise on 3 days/week for 48 weeks at a tribal wellness center. The program was divided into three, 16-week-long phases to test different financial incentive strategies. Within each phase participants were randomly assigned to one of two groups that received different payments for exercise. Phase 1 was designed to test whether the size of the incentive would affect exercise frequency. In Phase 1, the number of exercise sessions did not differ between the group receiving a modest fixed-value payment per exercise session and the group receiving enhanced incentives to exercise more frequently (26 ± 3 versus 28 ± 2 sessions, respectively, p = 0.568). In Phase 2, the provision of an enhanced financial incentive to increase exercise duration resulted longer sessions, as the incentivized and standard payment groups exercised 38 ± 2 versus 29 ± 1 minutes per session (p = 0.002), respectively. In Phase 3, the effect of reducing the incentives on maintenance of exercise behaviors was inconclusive due to high participant withdrawal. Aerobic fitness increased 10% during Phase 1 but was unchanged thereafter. Insulin sensitivity and body composition were unchanged during the study. In conclusion, enhanced financial incentives increased the duration of exercise sessions, but had minimal effects on exercise participation. These results indicate that financial incentives hold promise in motivating previously sedentary, overweight/obese adolescents to exercise longer, but motivating them to sustain an exercise program remains the major challenge.Trial Registration: ClinicalTrials.gov NCT01848353.

Background The prevalence and socioeconomic burden of childhood obesity and diabetes has increased rapidly in the United States in the last 30 years. American Indians have the highest prevalence of type 2 diabetes among newly diagnosed youth in the country. Contributing factors include environmental, behavioral, and genetic components. Some American Indian tribal communities have explored innovative ways to combat this epidemic including collaborations with academic centers on community-based research. Method From 2012 to 2017, the University of Oklahoma Health Science Center and the Choctaw Nation of Oklahoma partnered on a National Institutes of Health–funded project to determine if financial incentives would elicit an increase in physical activity in Native youth. This was a community-based behavioral intervention for overweight or obese American Indian youth ages 11–20 living in a rural community at risk for developing diabetes. Results Tribal leaders and staff identified culturally appropriate strategies to aid implementation of the trial in their community. Their identified implementation strategies helped standardize the study in order to maintain study integrity. The mutually agreed strategies included co-review of the study by tribal and University research review boards (but designation of the Choctaw Nation review board as the “Board of Record”), training of community-based staff on research ethics and literacy, standardization of the informed consent process by videotaping all study information, creation of a viable and culturally appropriate timeline for study implementation, adapting tribal wellness center operations to accommodate youth, and development of effective two-way communication through training sessions, on-site coordination, and bi-monthly conference calls. Conclusion In an effort to partner collectively on a randomized clinical research trial to combat childhood diabetes, tribal leaders and staff implemented strategies that resulted in a culturally appropriate and organized community-based behavioral intervention research project.

Circulating amino acids (AA) and their metabolites are biomarkers for insulin resistance and future diabetes in adults, but there are few, and conflicting findings in studies of adolescents. We performed amino acid metabolomic profiling in American Indian adolescents to determine whether specific analytes would vary with body composition and insulin sensitivity, and/or be altered in response to exercise training. Boys and girls, 11-18 years who were normal weight (NW, n=36) or obese (Ob, n=58) completed tests of fitness, body composition, and a fasting blood draw. Forty-two of the Ob group were retested after completing 16 weeks of aerobic exercise training. A panel of 42 plasma amino acids and metabolites were measured by UPLC/MS/MS. The Ob group had several risk factors for future diabetes, including higher body fat, lower aerobic fitness, and lower insulin sensitivity (iHOMA2). The Ob group had 16 analytes that were higher and 8 lower than the NW group. Among those that were higher in the Ob group were branched chain AAs (Val, Leu, Ile, +13-17%) and aromatic AAs (His, Phe, Tyr, +15-34%); those AAs were also correlated with body fat (r=0.32 to 0.53) and insulin sensitivity (r=-0.32 to -0.60). The Lys metabolite, α-aminoadipic acid, a predictor of diabetes in adults, was 46% higher in the Ob group and correlated with insulin sensitivity (r=-0.43). β-aminoisobutyric acid, a myokine related to insulin resistance in adults, was 29% lower in the Ob vs. the NW group and correlated with insulin sensitivity (r=0.32). Exercise training resulted in a 10% increase in aerobic fitness, but body composition and insulin sensitivity were unchanged. Only two AAs were changed (His, Cys) after training. These novel findings in adolescents demonstrate that several plasma AAs are altered by obesity and serve as biomarkers of insulin action, but are not altered with this exercise intervention. Disclosure K.R. Short: None. J. Chadwick: None. M.A. Tullier: None. L.D. Wolbert: None. C.L. Coleman: None. K.C. Copeland: Other Relationship; Self; Novo Nordisk Inc..

American Indians (AI) have high prevalence of diabetes, which might be reduced through targeted lifestyle changes. We conducted an exercise program for AI adolescents at risk for diabetes. We tested whether the participants’ perceptions of physical activity were related to their physical characteristics or exercise participation. Overweight (OW) AI youth (n = 75), 11-20 years old, with low physical activity, were instructed to exercise 3d/week for 16 weeks at tribal centers. Another 39 normal weight (NW) peers from the same communities served as a reference group but did not enter the exercise program. Perceived comfort and enjoyment of physical activity was measured on a 15-item, 5-point scale. Clinical tests included body composition, aerobic fitness (VO2pk), and physical activity (daily steps). Mean perception score was higher (more positive outlook) for NW than OW/Ob (4.1 ± 0.5 vs. 3.5 ± 0.6, p < 0.001) and for boys than girls (3.9 ± 0.5 vs. 3.5 ± 0.6, p < 0.02). Perception was negatively correlated with body mass index (r = -0.52), percent body fat and total fat free mass (r = -0.54 and -0.23, respectively), and positively correlated with VO2pk and daily steps (r = 0.53 and 0.38). OW participants completed 27 ± 15 exercise sessions, lasting 34 ± 7 minutes per session. Participants who completed at least 24 sessions had higher perception scores than those with less than 24 sessions (3.6 ± 0.6 vs. 3.3 ± 0.6, p=0.04). More OW participants reported perceived limitations to exercise (64%) and life stressors (85%) than the NW group (51% and 74%, respectively), but these barriers did not explain variance in exercise compliance. In AI adolescents, perception of physical activity varies with body weight, physical activity, and aerobic fitness, and may contribute to rates of participation in a wellness-center based exercise program. Thus, physical activity programs to reduce diabetes risk in this population must be tailored to address additional barriers related to one’s perceptions in order to to optimize participation. Disclosure H. Kimbley: None. J. Chadwick: None. C.L. Coleman: None. M.A. Tullier: None. L.D. Wolbert: None. K.C. Copeland: Other Relationship; Self; Novo Nordisk Inc.. K.R. Short: None.