Background: Lifestyle change is the cornerstone for preventing type 2 diabetes (T2D) in high risk populations. However, there is significant biological variability in how individuals respond. The purpose of this secondary analysis is to characterize response heterogeneity in high-risk youth after a lifestyle intervention that led to significant increases in insulin sensitivity.

Methods: Latino adolescents with obesity (N=90, age 15.4±0.9 y, BMI% 98.0±1.5) were enrolled in a 3-month lifestyle intervention and followed for 1 year. Insulin sensitivity (IS) was estimated by glucose and insulin response to OGTT at 0, 3, 6, and 12 months. Covariance pattern mixture models identified response phenotypes. Baseline T2D risk factors were compared among response phenotypes using one-way ANOVA.

Results: Four distinct response phenotypes were identified: Long-Term Responders (LTR, N=13), Short-Term Responders (STR, N=29), Slow Responders (SR, N=30), and Non-Responders (NR, N=18). LTRs exhibited the greatest increase in IS (β±SE linear, 0.51±0.2, p=0.002), STR exhibited early, non-significant increases in IS (-0.08±0.3, p=0.5), SRs exhibited a slow increase (0.09±0.03, p=0.002), and NR did not change over time (0.002±0.02, p=0.9). Attendance during the intervention was not different across response phenotypes (p=0.1) and groups did not differ by age (p=0.9) sex (p=0.5), or prediabetes status (p=0.2). Comparing baseline characteristics between the most extreme response phenotypes (NR vs. LTR), NR exhibited significantly lower IS (p<0.001) and higher BMI% (p=0.001), waist circumference (p=0.001), TRGs (p=0.006), fasting and 2-hr insulin (p<0.001), and 2-hr glucose (p=0.009) compared to LTR.

Conclusion: Results highlight the heterogeneous response to lifestyle intervention in Latino youth and suggest that the highest risk youth require more aggressive efforts to improve insulin sensitivity. Precision approaches are warranted to meet the T2D prevention needs in this population.


A. Pena: None. D. McNeish: None. S. Ayers: None. M. Olson: None. K.B. Vander Wyst: None. A. Williams: None. Y.P. Konopken: None. C. Keller: None. F. González Castro: None. D.L. Patrick: None. G.Q. Shaibi: None.


National Institute of Diabetes and Digestive and Kidney Diseases (R01DK10757901, 3R01DK107579-03S1); National Institute on Minority Health and Health Disparities (P20MD002316, U54MD002316)

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