Changes in proteomic cargo of circulating extracellular vesicles in response to lifestyle intervention in adolescents with hepatic steatosis.

BACKGROUND: Recent studies suggest that proteomic cargo of extracellular vesicles (EVs) may play a role in metabolic improvements following lifestyle interventions. However, the relationship between changes in liver fat and circulating EV-derived protein cargo following intervention remains unexplored. METHODS: The study cohort comprised 18 Latino adolescents with obesity and hepatic steatosis (12 males/6 females; average age 13.3 ± 1.2 y) who underwent a six-month lifestyle intervention. EV size distribution and concentration were determined by light scattering intensity; EV protein composition was characterized by liquid chromatography tandem-mass spectrometry. RESULTS: Average hepatic fat fraction (HFF) decreased 23% by the end of the intervention (12.5% [5.5] to 9.6% [4.9]; P = 0.0077). Mean EV size was smaller post-intervention compared to baseline (120.2 ± 16.4 nm to 128.4 ± 16.5 nm; P = 0.031), although the difference in mean EV concentration (1.1E+09 ± 4.1E+08 particles/mL to 1.1E+09 ± 1.8E+08 particles/mL; P = 0.656)) remained unchanged. A total of 462 proteins were identified by proteomic analysis of plasma-derived EVs from participants pre- and post-intervention, with 113 proteins showing differential abundance (56 higher and 57 lower) between the two timepoints (adj-p <0.05). Pathway analysis revealed enrichment in complement cascade, initial triggering of complement, creation of C4 and C2 activators, and regulation of complement cascade. Hepatocyte-specific EV affinity purification identified 40 proteins with suggestive (p < 0.05) differential abundance between pre- and post-intervention samples. CONCLUSIONS: Circulating EV-derived proteins, particularly those associated with the complement cascade, may contribute to improvements in liver fat in response to lifestyle intervention.

Preventing diabetes in Latino families: A protocol for a randomized control trial.

BACKGROUND: Latino families are disproportionately affected by type 2 diabetes (T2D) and lifestyle intervention is the first-line approach for preventing T2D. The purpose of this study is to test the efficacy of a culturally-grounded lifestyle intervention that prioritizes health promotion and diabetes prevention for Latino families. The intervention is guided by a novel Family Diabetes Prevention Model, leveraging the family processes of engagement, empowerment, resilience, and cohesion to orient the family system towards health. METHOD: Latino families (N = 132) will be recruited and assessed for glucose tolerance as measured by an Oral Glucose Tolerance Test (OGTT) and General and Weight-Specific Quality of Life (QoL) at baseline, four months, and 12 months. All members of the household age 10 and over will be invited to participate. Families will be randomized to the intervention group or a control group (2:1). The 16-week intervention includes weekly nutrition and wellness classes delivered by bilingual, bicultural Registered Dietitians and community health educators at a local YMCA along with two days/week of supervised physical activity classes and a third day of unsupervised physical activity. Control families will meet with a physician and a Registered Dietitian to discuss the results of their metabolic testing and recommend lifestyle changes. We will test the efficacy of a family-focused diabetes prevention intervention for improving glucose tolerance and increasing QoL and test for mediators and moderators of long-term changes. CONCLUSION: This study will provide much needed data on the efficacy of a family-focused Diabetes Prevention Program among high-risk Latino families.

Inflammatory Mediators and Type 2 Diabetes Risk Factors before and in Response to Lifestyle Intervention among Latino Adolescents with Obesity.

Obesity is associated with chronic inflammation that may contribute to T2D among youth. We examined the association between inflammatory biomarkers and insulin sensitivity and ß-cell function and response to lifestyle intervention among Latino youth with obesity. Latino youth (n = 64) were randomized to six months of lifestyle intervention (INT, n = 40) or usual care (UC, n = 24). INT included nutrition education and physical activity. UC involved meeting with a pediatric endocrinologist and registered dietitian to discuss healthy lifestyles. At baseline, multiple linear regression assessed fasting serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), high-molecular weight adiponectin (HMW Adpn), IL-10, IL-1 receptor antagonist (IL-1ra) as predictors of insulin sensitivity (whole-body insulin sensitivity index, WBISI) and ß-cell function (oral disposition index, oDI). Changes in outcomes between groups were assessed using covariance pattern models. At baseline, MCP-1 (ß ± SE, -0.12 ± 0.05, p = 0.027) and IL-1ra (-0.03 ± 0.01, p = 0.005) were negatively associated with WBISI. Treatment effects were not observed for inflammatory markers. WBISI was significantly increased among both INT (from 1.8 ± 0.2 to 2.6 ± 0.4, p = 0.005) and UC (from 1.6 ± 0.2 to 2.8 ± 0.5, p = 0.002) with no significant differences between the groups. Obesity-related inflammatory mediators were associated with T2D risk factors but were unaffected by lifestyle intervention among Latino youth.

Impact of overweight and obesity on epicardial adipose tissue in children with type 1 diabetes.

OBJECTIVES: Epicardial adipose tissue (EAT) thickness, a novel marker of cardiovascular disease (CVD), is increased in children with a healthy weight and type 1 diabetes (T1D). The prevalence of obesity has increased in children with T1D and may confer additional CVD risk. The purpose of this study was to examine EAT thickness in youth with and without T1D in the setting of overweight/obesity. METHODS: Youth with overweight/obesity and T1D (n=38) or without T1D (n=34) between the ages of 6-18 years were included in this study. Echocardiogram using spectral and color flow Doppler was used to measure EAT and cardiac function. Waist circumference, blood pressure, and HbA1c, were used to calculate estimated glucose disposal rate (eGDR) to estimate insulin resistance in children with T1D. RESULTS: EAT thickness was not significantly different in youth with T1D compared to controls (2.10 ± 0.67 mm vs. 1.90 ± 0.59 mm, p=0.19). When groups were combined, EAT significantly correlated with age (r=0.449, p≤0.001), BMI (r=0.538, p≤0.001), waist circumference (r=0.552, p≤0.001), systolic BP (r=0.247, p=0.036), myocardial performance index (r=-0.287, p=0.015), ejection fraction (r=-0.442, p≤0.001), and cardiac output index (r=-0.306, p=0.009). In the group with T1D, diastolic BP (r=0.39, p=0.02) and eGDR (r=-0.48, p=0.002) correlated with EAT. CONCLUSIONS: EAT was associated with measures of adiposity and insulin resistance but does not differ by diabetes status among youth with overweight/obesity. These findings suggest that adiposity rather than glycemia is the main driver of EAT thickness among youth with T1D.

Effects of a Diabetes Prevention Program on Type 2 Diabetes Risk Factors and Quality of Life Among Latino Youths With Prediabetes: A Randomized Clinical Trial.

Importance: Latino youths are disproportionately impacted by prediabetes and type 2 diabetes (T2D). Lifestyle intervention is the first-line approach for preventing or delaying T2D among adults with prediabetes. Objective: To assess the efficacy of a diabetes prevention program among Latino youths aged 12 to 16 years with prediabetes. Design, Setting, and Participants: This 2-group parallel randomized clinical trial with 2:1 randomization assessed a lifestyle intervention against usual care among Latino youths with prediabetes and obesity with 6- and 12-month follow-up. The study was conducted at YMCA facilities in Phoenix, Arizona from May 2016 to March 2020. Intervention: Participants were randomized to lifestyle intervention (INT) or usual care control (UCC). The 6-month INT included 1 d/wk of nutrition and health education and 3 d/wk of physical activity. UCC included 2 visits with a pediatric endocrinologist and a bilingual, bicultural registered dietitian to discuss diabetes risks and healthy lifestyle changes. Main Outcomes and Measures: Insulin sensitivity, glucose tolerance, and weight-specific quality of life (YQOL-W) at 6- and 12-month follow-up. Results: A total of 117 Latino youths (mean [SD] age, 14 [1] years; 47 [40.1%] girls) were included in the analysis. Overall, 79 were randomized to INT and 38 to UCC. At 6 months, the INT led to significant decreases in mean (SE) 2-hour glucose (baseline: 144 [3] mg/dL; 6 months: 132 [3] mg/dL; P = .002) and increases in mean (SE) insulin sensitivity (baseline: 1.9 [0.2]; 6 months: 2.6 [0.3]; P = .001) and YQOL-W (baseline: 75 [2]; 6 months: 80 [2]; P = .006), but these changes were not significantly different from UCC (2-hour glucose: mean difference, -7.2 mg/dL; 95% CI, -19.7 to 5.3 mg/dL; P for interaction = .26; insulin sensitivity: mean difference, 0.1; 95% CI, -0.7 to 0.9; P for interaction = .79; YQOL-W: mean difference, 6.3; 95% CI, -1.1 to 13.7; P for interaction = .10, respectively). Both INT (mean [SE], -15 mg/dL [4.9]; P = .002) and UCC (mean [SE], -15 mg/dL [5.4]; P = .005) had significant 12-month reductions in 2-hour glucose that did not differ significantly from each other (mean difference, -0.3; 95% CI, -14.5 to 14.1 mg/dL; P for interaction = .97). At 12 months, changes in mean (SE) insulin sensitivity in INT (baseline: 1.9 [0.2]; 12 months: 2.3 [0.2]; P = .06) and UCC (baseline: 1.9 [0.3]; 12 months: 2.0 [0.2]; P = .70) were not significantly different (mean difference, 0.3; 95% CI, -0.4 to 1.0; P for interaction = .37). At 12 months, YQOL-W was significantly increased in INT (basline: 75 [2]; 12 months: 82 [2]; P < .001) vs UCC (mean difference, 8.5; 95% CI, 0.8 to 16.2; P for interaction = .03). Conclusions and Relevance: In this randomized clinical trial, both INT and UCC led to similar changes in T2D risk factors among Latino youths with diabetes; however, YQOL-W was improved in INT compared with UCC. Diabetes prevention interventions that are effective in adults also appeared to be effective in high risk youths. Trial Registration: ClinicalTrials.gov Identifier: NCT02615353.

Organ fat in Latino youth at risk for type 2 diabetes.

PURPOSE: Obesity in youth increases the risk for type 2 diabetes (T2D) and elevated abdominal adipose tissue and organ fat may be particularly deleterious. The purpose of this study was to examine associations among measures of adiposity including total, visceral, and organ fat (hepatic and pancreatic) and whether these measures were independently associated with glycemia in Latino youth at risk for diabetes. METHODS: Latino adolescents (47 boys and 32 girls, 13.7 ± 1.4 years) with obesity (BMIz 2.3 ± 0.3) were assessed for total fat by DXA and visceral and organ fat by 3 T magnetic resonance imaging. Glycemic indicators included HbA1c, fasting glucose (FG), and 2-h glucose (2-HrG) following an oral glucose tolerance test. Pearson correlations and stepwise linear regression analyses controlling for age and sex were used to examine independent associations between adiposity and glycemia. RESULTS: Total fat was associated with visceral (r = 0.66, p = 0.001) and hepatic fat (r = 0.34, p < 0.01) while visceral fat was associated with hepatic (r = 0.42, p < 0.001) and pancreatic fat (r = 0.36, p < 0.001). In stepwise linear regression analysis, hepatic and pancreatic fat were significant predictors of FG, explaining 4.7% and 5.2% of the variance, respectively (total R2  = 0.14, p = 0.02). Hepatic fat was the only significant predictor of 2-HrG explaining 9.9% of the variance in the model (total R2  = 0.12, p = 0.03). No measure of adiposity was retained as a significant predictor of HbA1c. CONCLUSION: Hepatic and pancreatic fat were the only adiposity measures independently associated with glycemia but the small amount of variance explained underscores the need for additional T2D biomarkers in high risk youth.

Changes in OGTT-derived biomarkers in response to lifestyle intervention among Latino adolescents with obesity.

BACKGROUND: Glucose concentrations during an oral glucose tolerance test (OGTT) have been used as biomarkers to differentiate type 2 diabetes risk phenotypes. No studies have examined changes in OGTT-glucose phenotypes following lifestyle intervention among high-risk youth. OBJECTIVE: To examine changes in OGTT-glucose phenotypes following lifestyle intervention and to explore differences in insulin sensitivity and ß-cell function among post-intervention phenotypes. METHODS: Latino adolescents with obesity (n = 48, age 15.4 ± 1.0, BMI% 98.2 ± 1.4, female 56.3%) completed a 12-week lifestyle intervention that included weekly nutrition education and physical activity. At baseline and 12 weeks, youth completed a 2-h OGTT with glucose and insulin concentrations assessed at 0', 30', 60', 90' and 120'. Glucose concentrations during the OGTT were used to identify biomarkers, 1-h glucose, glucose response curve and time to glucose peak. Using these respective biomarkers, high-risk (1-h glucose ≥ 155 mg/dl, Monophasic, Late Peak) and lower-risk phenotypes (1-h glucose < 155 mg/dl, Biphasic, Early Peak) were categorized. Insulin sensitivity was estimated by whole-body insulin sensitivity index (WBISI) and ß-cell function by oral disposition index (oDI). RESULTS: Following intervention, the prevalence of Monophasic phenotypes decreased from 81% to 67% (p = 0.048) and 1-h glucose ≥ 155 mg/dl from 38% to 10% (p = 0.054). Although Late Peak phenotypes did not significantly change (from 58% to 29%, p = 0.200), Early Peak phenotypes at post-intervention demonstrated significantly higher WBISI compared to Late Peak (2.3 ± 0.1 vs 1.7 ± 0.2, p = 0.023). CONCLUSIONS: OGTT-glucose phenotypes improve following lifestyle intervention among high-risk youth. These findings further support their potential utility as clinical biomarkers to identify diabetes risk and risk reduction in youth.

Communicating incidental and reportable findings from research MRIs: considering factors beyond the findings in an underrepresented pediatric population.

BACKGROUND: The application of advanced imaging in pediatric research trials introduces the challenge of how to effectively handle and communicate incidental and reportable findings. This challenge is amplified in underserved populations that experience disparities in access to healthcare as recommendations for follow-up care may be difficult to coordinate. Therefore, the purpose of the present report is to describe the process for identifying and communicating findings from a research MRI to low-income Latino children and families. METHODS: Latino adolescents (n = 86) aged 12-16 years old with obesity and prediabetes underwent a research MRI (3 Tesla Philips Ingenia®) as part of a randomized controlled diabetes prevention trial. The research MRIs were performed at baseline and 6 months to assess changes in whole-abdominal fat distribution and organ fat in response to the intervention. An institutional pathway was developed for identifying and reporting findings to participants and families. The pathway was developed through a collaborative process with hospital administration, research compliance, radiology, and the research team. All research images were reviewed by a board-certified pediatric radiologist who conveyed findings to the study pediatrician for determination of clinical actionability and reportability to children and families. Pediatric sub-specialists were consulted as necessary and a primary care practitioner (PCP) from a free community health clinic agreed to receive referrals for uninsured participants. RESULTS: A total of 139 images (86 pre- and 53 post-intervention) were reviewed with 31 findings identified and 23 deemed clinically actionable and reportable. The only reportable finding was severely elevated liver fat (> 10%, n = 14) with the most common and concerning incidental findings being horseshoe kidney (n = 1) and lung lesion (n = 1). The remainder (n = 7) were less serious. Of youth with a reportable or incidental finding, 18 had a PCP but only 7 scheduled a follow-up appointment. Seven participants without a PCP were referred to a safety-net clinic for follow-up. CONCLUSIONS: With the increased utilization of high-resolution imaging in pediatric research, additional standardization is needed on what, when, and how to return incidental and reportable findings to participants, particularly among historically underrepresented populations that may be underserved in the community. TRIAL REGISTRATION: Preventing Diabetes in Latino Youth, NCT02615353.

Bone marrow adipose tissue content in Latino adolescents with prediabetes and obesity.

OBJECTIVE: This study aimed to examine whether total, regional, and organ fat predicts bone marrow adipose tissue (BMAT) fat content and to explore whether BMAT fat content differs by sex among Latino youth. METHODS: Latino youth (n = 86; age 13.6 [1.4] years, 62% male) with obesity (BMI percentile = 98.5% [1.2%]) underwent a dual-energy x-ray absorptiometry scan to assess body composition and a magnetic resonance imaging scan to determine abdominal adiposity, liver fat, and vertebral BMAT fat content in the thoracic (average of T8-T12) and lumbar (average of L1-L5) spine. RESULTS: Male youth exhibited significantly greater thoracic (male youth = 30.8% [1.4%] vs. female youth = 24.5% [2.1%], p = 0.027) and lumbar (male youth = 36.3% [1.5%] vs. female youth = 30.2% [2.2%], p = 0.038) BMAT fat content compared with female youth. Visceral adipose tissue was a significant predictor of thoracic (ß = 0.434, t[86] = 3.016, p = 0.003) and lumbar (ß = 0.389, t[86] = 2.677, p = 0.009) BMAT fat content, explaining 8.9% and 6.9% of the variance, respectively. Liver fat was a significant predictor of both thoracic (ß = 0.487, t[86] = 4.334, p < 0.001) and lumbar (ß = 0.436, t[86] = 3.793, p < 0.001) BMAT fat content, explaining 17.6% and 13.8% of the variance, respectively. CONCLUSIONS: Male youth had significantly greater thoracic and lumbar BMAT fat content than female youth. Greater BMAT fat content is associated with greater liver fat and visceral adipose tissue among youth with obesity. Further investigation of the mechanistic underpinnings of BMAT may help to differentiate its metabolic and bone-related functions.

Theoretical Mediators of Diabetes Risk and Quality of Life Following a Diabetes Prevention Program for Latino Youth With Obesity.

PURPOSE: This study tested self-efficacy and social support for activity and dietary changes as mediators of changes in type 2 diabetes related outcomes following a lifestyle intervention among Latino youth. SETTING AND INTERVENTION: Latino adolescents (14-16 years) with obesity (BMI% = 98.1 ± 1.4) were randomized to a 3-month intervention (n = 67) that fostered self-efficacy and social support through weekly, family-centered sessions or a comparison condition (n = 69). MEASURES: Primary outcomes included insulin sensitivity and weight specific quality of life. Mediators included self-efficacy, friend, and family social support for health behaviors. Data was collected at baseline, 3-months, 6-months, and 12-months. ANALYSIS: Sequential path analysis was used to examine mediators as mechanisms by which the intervention influenced primary outcomes. RESULTS: The intervention had a direct effect on family (ß = 0.33, P < .01) and friend social support (ß = 0.22, P < .001) immediately following the intervention (3-months). Increased family social support mediated the intervention's effect on self-efficacy at 6-months (ß = 0.09, P < .01). However, social support and self-efficacy did not mediate long-term changes in primary outcomes (P > .05) at 12-months. CONCLUSIONS: Family social support may improve self-efficacy for health behaviors in high-risk Latino youth, highlighting the important role of family diabetes prevention. Fostering family social support is a critical intervention target and more research is needed to understand family-level factors that have the potential to lead to long-term metabolic and psychosocial outcome in vulnerable youth.

Relationship of Circulating Endothelial Cells With Obesity and Cardiometabolic Risk Factors in Children and Adolescents.

Background Circulating endothelial cells (CECs) reflect early changes in endothelial health; however, the degree to which CEC number and activation is related to adiposity and cardiovascular risk factors in youth is not well described. Methods and Results Youth in this study (N=271; aged 8-20 years) were classified into normal weight (body mass index [BMI] percentage <85th; n=114), obesity (BMI percentage ≥95th to <120% of the 95th; n=63), and severe obesity (BMI percentage ≥120% of the 95th; n=94) catagories. CEC enumeration was determined using immunohistochemical examination of buffy coat smears and activated CEC (percentage of vascular cell adhesion molecule-1 expression) was assessed using immunofluorescent staining. Cardiovascular risk factors included measures of body composition, blood pressure, glucose, insulin, lipid profile, C-reactive protein, leptin, adiponectin, oxidized low-density lipoprotein cholesterol, carotid artery intima-media thickness, and pulse wave velocity. Linear regression models examined associations between CEC number and activation with BMI and cardiovascular risk factors. CEC number did not differ among BMI classes (P>0.05). Youth with severe obesity had a higher degree of CEC activation compared with normal weight youth (8.3%; 95% CI, 1.1-15.6 [P=0.024]). Higher CEC number was associated with greater body fat percentage (0.02 per percentage; 95% CI, 0.00-0.03 [P=0.020]) and systolic blood pressure percentile (0.01 per percentage; 95% CI, 0.00-0.01 [P=0.035]). Higher degree of CEC activation was associated with greater visceral adipose tissue (5.7% per kg; 95% CI, 0.4-10.9 [P=0.034]) and non-high-density lipoprotein cholesterol (0.11% per mg/dL; 95% CI, 0.01-0.21 [P=0.039]). Conclusions Methods of CEC quantification are associated with adiposity and cardiometabolic risk factors and may potentially reflect accelerated atherosclerosis as early as childhood.

A quality improvement project for managing hypocalcemia after pediatric total thyroidectomy.

Objectives Hypocalcemia following total thyroidectomy (TT) is relatively common. It may result in significant morbidity, prolonged hospital stay, and increased costs. Treatment with intravenous (IV) calcium gluconate may also carry significant risks. In pediatrics, management consensus guidelines are lacking. Methods At Phoenix Children's Hospital, a team of pediatric endocrinologists, surgeons and otolaryngologists developed a clinical pathway for patients undergoing TT. It was a Quality Improvement (QI) project with the primary aim of decreasing IV calcium gluconate use from a baseline of 68% to less than 40% over 15 months. Secondary aims included reducing hypocalcemia and length of hospitalization. Interventions included sending weekly pathway reminder emails, starting pre-operative calcium, and pathway implementation into the electronic health record. Results Twenty-seven patients underwent TT over 15 months. IV calcium gluconate use dropped to 48%. Hypocalcemia and length of hospitalization were 96% and 52.7 h (range 21.1-115.7) respectively. Pathway adherence improved after targeted interventions. Eleven (73%) of the 15 patients whose post-operative parathyroid hormone (PTH) nadir was below 15 pg/mL required IV calcium gluconate vs. two (17%) out of 12 with levels above this threshold. Conclusions Standardizing care allowed for objective outcome analysis. We learned that post-operative serum PTH level was the main risk factor for requiring IV calcium gluconate. Implementing the pathway as a QI project allows for revisions based on outcomes, ultimately resulting in a pathway that best utilizes our infrastructure to optimize care. Other pediatric institutions may face similar challenges and can potentially learn from our experience.

Response heterogeneity to lifestyle intervention among Latino adolescents.

OBJECTIVE: To characterize the heterogeneity in response to lifestyle intervention among Latino adolescents with obesity. METHODS: We conducted secondary data analysis of 90 Latino adolescents (age 15.4 ± 0.9 y, female 56.7%) with obesity (BMI% 98.1 ± 1.5%) that were enrolled in a 3 month lifestyle intervention and were followed for a year. Covariance pattern mixture models identified response phenotypes defined by changes in insulin sensitivity as measured using a 2 hour oral glucose tolerance test. Baseline characteristics were compared across response phenotypes using one-way ANOVA and chi-square test. RESULTS: Three distinct response phenotypes (PH1, PH2, PH3) were identified. PH1 exhibited the most robust response defined by the greatest increase in insulin sensitivity over time (ß ± SE, linear 0.52 ± 0.17, P < .001; quadratic -0.03 ± 0.01, P = .001). PH2 showed non-significant changes, while PH3 demonstrated modest short-term increases in insulin sensitivity which were not sustained over time (linear 0.08 ± 0.03, P = .002; quadratic -0.01 ± 0.002, P = .003). At baseline, PH3 (1.1 ± 0.4) was the most insulin resistant phenotype and exhibited the highest BMI% (98.5 ± 1.1%), 2 hours glucose concentrations (144.0 ± 27.5 mg/dL), and lowest beta-cell function as estimated by the oral disposition index (4.5 ± 2.8). CONCLUSION: Response to lifestyle intervention varies among Latino youth with obesity and suggests that precision approaches are warranted to meet the prevention needs of high risk youth.

Yields and costs of recruitment methods with participant phenotypic characteristics for a diabetes prevention research study in an underrepresented pediatric population.

BACKGROUND/AIMS: Prediabetes and diabetes disproportionately impact Latino youth, yet few diabetes prevention programs have prioritized inclusion of this underrepresented population. This report describes the recruitment process, yields, associated costs, and phenotypic characteristics of Latino youth with obesity and prediabetes enrolled in a randomized controlled diabetes prevention study in the USA. METHODS: Recruitment efforts included referrals from clinics, community outlets, local media, and word of mouth with the goal of enrolling 120 Latino adolescents aged 12-16 with obesity (BMI > 95th percentile) and prediabetes. Prediabetes eligibility was determined by any of the following: HbA1c between 5.7 and 6.5%, fasting glucose between 100 and 125 mg/dL, or a 2-h glucose between 120 and 199 mg/dL following a 75-g oral glucose tolerance test (OGTT), but not meeting any of the diagnostic criteria for diabetes. Eligible participants were randomized 2:1 to either a 6-month community-based lifestyle intervention that included group nutrition and health education classes (1 day/week) and group exercise classes (2 days/week) or usual care control arm. Recruitment yields were determined by review of referral source in the study screening database. Recruitment costs were determined by an after-the-fact financial review of actual and in-kind costs. Participant phenotypic characteristics (i.e., demographics, anthropometrics, and biochemical data) were compared by recruitment strategy using a one-way ANOVA. RESULTS: Recruitment efforts covered 160 mile2 (414 km2) across 26 ZIP codes (postcode) in the Phoenix Metropolitan Area and yielded 655 referrals from clinics (n = 344), community (n = 143), media (n = 137), and word-of-mouth (n = 31). From this pool, 26% (n = 167) did not meet general, pre-screening eligibility criteria; 29% (n = 187) declined participation; and 10% (n = 64) were unable to be contacted. A total of 237 youth were invited to the clinical research unit to determine final eligibility. Following the OGTT, 52% (n = 122) met prediabetes criteria and 117 were subsequently randomized. Clinical recruitment yielded the highest number of referrals (53%; n = 344) while word-of-mouth yielded the highest proportion (35%; n = 11) of randomized participants per referred youth. There were no significant differences in anthropometric or biochemical measures among youth by recruitment strategy. Based upon final enrollment numbers, community recruitment was the costliest approach ($486/randomized participant) followed by clinical ($248/randomized participant) and media ($236/randomized participant). CONCLUSIONS: The ability to meet enrollment goals for a clinical trial of an underrepresented population required multiple recruitment strategies. Although strategies vary in yields and costs, it appears they produce similar phenotypical risk profiles of eligible youth. TRIAL REGISTRATION: ClinicalTrials.gov NCT02615353 . Registered on 26 November 2015.

Familism, Self-Esteem, and Weight-Specific Quality of Life Among Latinx Adolescents With Obesity.

OBJECTIVE: Obesity is a critical public health condition affecting Latinx adolescents and contributes to health disparities across the lifespan. Childhood and adolescent obesity is associated with reduced quality of life (QoL) and decreased self-esteem. The purpose of this study is to examine the role of cultural (e.g., familism) and psychosocial (e.g., self-esteem) factors as predictors of weight-specific QoL among Latinx adolescents with obesity. METHODS: Baseline data from 160 Latinx adolescents (ages 14-16 years) with obesity (BMI > 95th percentile for age and sex) who were recruited for a diabetes prevention intervention were used. Structural equation modeling tested the relationships between four latent constructs (familism, positive self-esteem, self-deprecation, and weight-specific QoL). RESULTS: The model tested paths from familism to positive self-esteem, self-deprecation, and weight-specific QoL, and paths from positive self-esteem and self-deprecation to weight-specific QoL. Higher familism was positively associated with positive self-esteem but not self-deprecation. In turn, positive self-esteem was positively associated with higher weight-specific QoL, whereas self-deprecation was negatively associated. Furthermore, there was an indirect effect of familism on QoL via positive self-esteem. CONCLUSIONS: These data shed light into specific cultural and psychosocial constructs that influence QoL among Latinx adolescents with obesity. This study suggests that familism and positive self-esteem can operate as protective factors associated with higher weight-specific QoL in Latinx adolescents with obesity; whereas self-deprecation may operate as a risk factor for lower weight-specific QoL.

Sex as a moderator of body composition following a randomized controlled lifestyle intervention among Latino youth with obesity.

BACKGROUND: Body composition differences between males and females emerge during adolescence and continue throughout adulthood; however, whether sex moderates body composition changes in adolescents with obesity after an intervention is unknown. OBJECTIVE: To examine sex as a moderator of changes in adiposity following lifestyle intervention. METHODS: A total of 136 Latino youth with obesity (BMI% 98.2 ± 1.3) aged 14 to 16 years old were randomized to either a 12-week lifestyle intervention (27 males/40 females) or control (35 males/34 females) group. The intervention included nutrition education (1 h/wk) and moderate-to-vigorous physical activity (3 h/wk). Anthropometric data (body mass index [BMI], BMI%, waist circumference, total body fat, and fat-free mass) were obtained pre- and post-intervention. Sex differences were examined by general linear models with significance determined at P < .05 for the F-statistic. RESULTS: Sex did not moderate changes in BMI (F1,115 = 0.01, P = .9), BMI% (F1,115 = 0.14, P = .7), or waist circumference (F1,117 = 1.1, P = .3). Sex significantly moderated changes in body fat percent (F1,117 = 5.3, P = .02), fat mass (F1,116 = 4.5, P = .04), and fat-free mass (F1,116 = 4.3, P = .04). Intervention males compared with females had greater relative reductions in fat percent (-4.1 ± 0.8% vs -1.2 ± 0.7%, P = .02) and fat mass (-5.0 ± 1.1 kg vs -1.5 ± 0.9 kg, P = .02) and gained more fat free mass (3.6 ± 0.9 kg vs 0.5 ± 0.8 kg, P = .02) when compared with same sex controls. CONCLUSION: Males and females exhibited a differential response to lifestyle intervention for percent fat, fat mass, and fat-free mass indicating that sex-specific improvements in body composition favours males over females.

Evaluating a pragmatic estimate of insulin sensitivity in Latino youth with obesity.

The whole-body insulin sensitivity index (WBISI) is a widely used surrogate of insulin sensitivity estimated from glucose and insulin concentrations during an oral glucose tolerance test (OGTT). The original WBISI uses five timepoints but reduced sampling models have been proposed. These reduced models have not been applied to the paediatric population. The purpose of this study is to compare cross-sectional agreement and changes in response to lifestyle intervention between the original WBISI and the WBISI120 using fasting and 2-hour glucose and insulin concentrations from OGTT among Latino adolescents with obesity. We also examined the cost-differential between the two measures. Secondary analyses were conducted with data from Latino adolescents (14-16 years) with obesity (BMI ≥ 95th percentile) who were recruited for a randomized controlled lifestyle intervention trial. Baseline data in youth (n = 148) who underwent a 2-hour OGTT was used to analyse agreement between WBISI and WBISI120 . Data from 65 participants who completed a 12-week lifestyle intervention were used to assess changes and the rate of change between WBISI and WBISI120 . Research costs to determine both measures were compared. WBISI120 showed good cross-sectional agreement (ICCagreement = 0.88) with the full WBISI. Following intervention, WBISI120 increased 62.5% (M ± SD, 1.6 ± 1.2 to 2.6 ± 1.7, P < .001) while WBISI increased by 25.0% (1.6 ± 1.0 to 2.0 ± 1.0, P < .001) but the rate of change for WBISI and WBISI120 was not significantly different (P = .11). WBISI120 costs ~70% less than WBISI. WBISI120 may offer a cost-effective surrogate estimate of insulin sensitivity in Latino youth with obesity.

Epicardial adipose thickness in youth with type 1 diabetes.

BACKGROUND AND OBJECTIVE: Epicardial adipose thickness (EAT) is increased in adults with type 1 diabetes (T1D) and is thought to contribute to cardiovascular disease (CVD) in this population. Given that CVD risk factors emerge early in life, the purpose of this study was to identify whether EAT is increased in pediatric patients with T1D compared with non-diabetic controls. METHODS: Anthropometric data, blood pressure (BP), and EAT were evaluated in 20 youth with T1D and 20 age, sex, and body mass index (BMI) matched healthy controls between the ages of 5 and 18 years. RESULTS: EAT was 18.5% higher among youth with T1D compared to healthy controls (1.65 ± 0.44 mm vs 1.37 ± 0.27 mm, P = .02). In the entire cohort, EAT was correlated with age (r = 0.71, P < .001), BMI (r = .69, P < .001), waist circumference (r = 0.60, P < .001), systolic BP (r = .34, P = .03), and diastolic BP (r = 0.41, P = .009). Among youth with T1D, there were no significant correlations between EAT and HbA1c (r = -0.16, P = .50), insulin dose (r = .09, P = .71), or duration of disease (r = 0.06, P = .82). CONCLUSIONS: Youth with T1D exhibited significantly higher EAT compared to controls. Increased EAT was associated with adiposity and BP, but not duration of disease, insulin dose, or glycemic control. Increased EAT may represent a pathophysiologic mechanism leading to premature CVD in pediatric patients with T1D.

Decreased GlycA after lifestyle intervention among obese, prediabetic adolescent Latinos.

BACKGROUND: Obese youth with prediabetes are at increased risk for premature morbidity and mortality through multiple mechanisms, including increased systemic inflammation. GlycA is a novel measure of systemic inflammation that predicts type II diabetes, cardiovascular events, and all-cause mortality in adults. OBJECTIVE: The purpose of the present study was to examine changes in GlycA after lifestyle intervention among obese, prediabetic Latino youth. METHODS: Obese, prediabetic Latino youth (n = 27; 15.5 ± 1.1 years, 13 males/14 females) completed a 12-week lifestyle intervention that included weekly nutrition education and 3 d/wk of moderate to vigorous physical activity. Prediabetes was characterized by an expanded definition of impaired glucose tolerance, using 2-hour glucose ≥120 mg/dL after an oral glucose tolerance test. GlycA was assessed at baseline and 12 weeks using nuclear magnetic resonance spectroscopy. RESULTS: After the lifestyle intervention, GlycA was significantly reduced (445.3 ± 51.3 µmol/L to 419.0 ± 50.0 µmol/L, P = .01) (mean ± standard deviation). Additional improvements were observed in multiple cardiovascular risk factors, including body mass index (BMI; 34.8 ± 5.0 kg/m2 to 34.0 ± 5.1 kg/m2, P < .001), total cholesterol (154.1 ± 30.3 mg/dL to 143.3 ± 29.1 mg/dL, P = .003), and 2-hour glucose (141.0 ± 13.2 mg/dL to 115.9 ± 31.4 mg/dL, P < .001). Decreases in GlycA were associated with decreases in 2-hour glucose (r = 0.49, P = .008) and BMI (r = 0.41, P = .03). CONCLUSION: These data are consistent with the hypothesis that lifestyle intervention might improve GlycA levels in obese, prediabetic adolescent Latinos, but randomized trial evidence is needed. Healthy lifestyle modifications among high-risk youth may decrease future risk of cardiometabolic disease through reducing systemic inflammation, in addition to improving traditional cardiovascular risk factors.

Effects of a lifestyle intervention on markers of cardiometabolic risk and oxidized lipoproteins among obese adolescents with prediabetes.

OBJECTIVE: Obesity and hyperglycaemia contribute to the atherosclerotic process in part through oxidative modifications to lipoprotein particles. The present study aimed to evaluate the effects of a lifestyle intervention on markers of oxidized lipoproteins in obese Latino adolescents with prediabetes. DESIGN: Pre-post design. SETTING: Participants were enrolled into a 12-week lifestyle intervention. Measurements pre- and post-intervention included anthropometrics and body composition, lipid panel, oxidized LDL (oxLDL), oxidized HDL (oxHDL), intake of fresh fruits and vegetables, and cardiorespiratory fitness. PARTICIPANTS: Thirty-five obese Latino adolescents (seventeen females, eighteen males; mean age 15·5 (sd 1·0) years; mean BMI percentile 98·5 (sd 1·2)) with prediabetes. RESULTS: Intervention participation resulted in significant reductions in weight (-1·2 %, P = 0·042), BMI and BMI percentile (-2·0 and -0·4 %, respectively, P < 0·001), body fat (-7·0 %, P = 0·025), TAG (-11·8 %, P = 0·032), total cholesterol (-5·0 %, P = 0·002), VLDL-cholesterol (-12·5 %, P = 0·029), and non-HDL-cholesterol (-6·7 %, P = 0·007). Additionally, fitness (6·4 %, P < 0·001) and intake of fruits and vegetables (42·4 %, P = 0·025) increased significantly. OxLDL decreased significantly after the intervention (51·0 (sd 14·0) v. 48·7 (sd 12·8) U/l, P = 0·022), while oxHDL trended towards a significant increase (395·2 (sd 94·6) v. 416·1 (sd 98·4) ng/ml, P = 0·056). CONCLUSIONS: These data support the utility of lifestyle intervention to improve the atherogenic phenotype of Latino adolescents who are at high risk for developing premature CVD and type 2 diabetes.