Latino youth are disproportionately impacted by obesity, prediabetes and type 2 diabetes (T2D). Pediatric obesity is characterized by abnormal increases in pro-inflammatory markers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) and reductions in anti-inflammatory markers, high molecular weight adiponectin (HMW Adpn) and interleukin-10 (IL-10). Interleukin-1 receptor antagonist (IL-1ra) is an anti-inflammatory that is positively associated with obesity. IL-6, TNF-α, MCP-1 and IL-1ra have been associated with reduced insulin sensitivity and β-cell dysfunction, two central pathophysiologic mediators of glucose intolerance, while HMW Adpn and IL-10 have been associated with increased insulin sensitivity and β-cell function. The United States Diabetes Prevention Program (DPP) supported lifestyle intervention as the cornerstone approach for preventing T2D among adults with prediabetes, yet no studies to date have assessed the efficacy of an adapted DPP among Latino youth with prediabetes. In this dissertation, three studies were conducted. The first cross-sectional study among Latino youth with prediabetes and obesity (n=65) demonstrated that MCP-1 (β=-0.001, p=0.027; β=0.03, p=0.033), HMW Adpn (β=0.2, p<0.001; β=-2.2, p=0.018), and IL-1ra (β=-0.03, p=0.006; β=0.09, p=0.009) significantly predicted insulin sensitivity (measured by whole body insulin sensitivity index, WBISI) and glucose tolerance (measured by 2-hr glucose concentrations from an oral glucose tolerance test), respectively. Only HMW Adpn significantly predicted β-cell function, measured by oral disposition index, or oDI (β=0.6, p<0.001). The second study was a randomized control trial that demonstrated the efficacy of lifestyle intervention (INT, n=79) for improving oDI among Latino youth with prediabetes and obesity, compared to a usual care control (UCC, n=38) group. No differences were found for changes in WBISI (Δ0.1, p=0.899) or 2-hr glucose (Δ-7.2, p=0.260) between groups. The third study was a secondary analysis (INT n=46, UCC n=29) that demonstrated no significant effects on IL-6, TNF-α, MCP-1, HMW Adpn, IL-10, or IL-1ra (all interactions, p>0.05).

Background. Effects of lifestyle interventions on early biomarkers of oxidative stress and CVD risk in youth with prediabetes are unknown. Objective. To evaluate the effects of a lifestyle intervention to prevent type 2 diabetes among obese prediabetic Latino adolescents on oxidized lipoproteins. Design: In a quasi-experimental design, 35 adolescents (51.4% male, age 15.5(1.0) y, body mass index (BMI) percentile 98.5(1.2), and glucose 2 hours after an oral glucose tolerance test-OGTT 141.2(12.2) mg/dL) participated in a 12-week intervention that included weekly exercise (three 60 min-sessions) and nutrition education (one 60 min-session). Outcomes measured at baseline and post-intervention were: fasting oxidized LDL and oxidized HDL (oxLDL and oxHDL) as oxidative stress variables; dietary intake of fresh fruit and vegetable (F&V) and fitness (VO2max) as behavioral variables; weight, BMI, body fat, and waist circumference as anthropometric variables; fasting glucose and insulin, 2hour glucose and insulin after an OGTT, insulin resistance (HOMA-IR), and lipid panel (triglycerides, total cholesterol, VLDL-c, LDL-c, HDL-c, and Non-HDL) as cardiometabolic variables. Results. Comparing baseline to post-intervention, significant decreases in oxLDL concentration were shown (51.0(14.0) and 48.7(12.8) U/L, p=0.022); however, the intervention did not decrease oxHDL (395.2(94.6) and 416.1(98.4) ng/mL, p=0.944). F&V dietary intake (116.4(97.0) and 165.8(91.0) g/d, p=0.025) and VO2max (29.7(5.0) and 31.6(4.7) ml*kg-1*min-1, p<0.001) significantly increased. Within-subjects correlations between changes in F&V intake and oxidized lipoproteins, adjusted for VO2max changes, were non-significant (R=-0.15, p=0.52 for oxLDL; R=0.22, p=0.25 for oxHDL). Anthropometric variables were significantly reduced (weight -1.3% p=0.042; BMI -2.2% and BMI percentile -0.4%, p=0.001; body fat -6.6% and waist circumference -1.8%, p=0.025). Cardiometabolic variables significantly improved, including reductions in glucose 2hour (-19.3% p<0.001), fasting insulin (-12.9% p=0.008), insulin 2hour (-53.5% p<0.001), and HOMA-IR (-12.5% p=0.015), with 23 participants (66%) that reverted toward a normal glucose tolerance status. Most lipid panel significantly changed (triglycerides -10.2% p=0.032; total cholesterol -5.4% p=0.002; VLDL-c -10.4% p=0.029; HDL-c -3.2% p=0.022; and Non-HDL -5.5% p=0.0007). Conclusion. The intervention resulted in differential effects on oxidized lipoproteins and significant improvements in behavioral, anthropometric and cardiometabolic variables, reducing the high metabolic risk of obese prediabetic kids.