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Obesity is associated with chronic inflammation that may contribute to T2D among youth. We examined the association between inflammatory biomarkers and insulin sensitivity and β-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 β-cell function (oral disposition index, oDI). Changes in outcomes between groups were assessed using covariance pattern models. At baseline, MCP-1 (β ± 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.

Growth mixture models (GMMs) are applied to intervention studies with repeated measures to explore heterogeneity in the intervention effect. However, traditional GMMs are known to be difficult to estimate, especially at sample sizes common in single-center interventions. Common strategies to coerce GMMs to converge involve post hoc adjustments to the model, particularly constraining covariance parameters to equality across classes. Methodological studies have shown that although convergence is improved with post hoc adjustments, they embed additional tenuous assumptions into the model that can adversely impact key aspects of the model such as number of classes extracted and the estimated growth trajectories in each class. To facilitate convergence without post hoc adjustments, this paper reviews the recent literature on covariance pattern mixture models, which approach GMMs from a marginal modeling tradition rather than the random effect modeling tradition used by traditional GMMs. We discuss how the marginal modeling tradition can avoid complexities in estimation encountered by GMMs that feature random effects, and we use data from a lifestyle intervention for increasing insulin sensitivity (a risk factor for type 2 diabetes) among 90 Latino adolescents with obesity to demonstrate our point. Specifically, GMMs featuring random effects--even with post hoc adjustments--fail to converge due to estimation errors, whereas covariance pattern mixture models following the marginal model tradition encounter no issues with estimation while maintaining the ability to answer all the research questions. [For the corresponding grantee submission, see ED618691.]

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 ([beta] ± SE, linear 0.52 ± 0.17, P < 0.001; quadratic -0.03 ± 0.01, P = 0.001). 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 = 0.002; quadratic -0.01 ± 0.002, P = 0.003). 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.

Background: Few studies have examined 24-hour activity and sleep behaviors and their contribution to type 2 diabetes (T2D) in Latino adolescents and young adults with obesity. Aim: This study included quantitative data on T2D risk and 24-hour activity and sleep behaviors and qualitative data on individual, social, and environmental behavioral determinants. Method: A 7 day, 24-hour, wrist-worn accelerometer protocol assessed moderate-to-vigorous physical activity (PA), sedentary behaviors (SB), sleep, and sleep regularity, in adolescents (N = 38; 12-16 years) and young adults (N = 22; 18-22 years). T2D-related outcomes included adiposity (BMI, BF%, waist circumference), fasting, and 2-hour glucose. A subsample of participants (N = 16 adolescents, N = 15 young adults) completed interviews to identify behavioral determinants. Results: High levels of PA were observed among adolescents (M = 103.8 ± 67.5 minutes/day) and young adults (M = 96.8 ± 78.8 minutes/day) as well as high levels of SB across both age groups ([greater than or equal to] 10 hours/day). Sleep regularity was negatively associated with adiposity (all ps < 0.05) in both age groups as well as fasting and 2-hour glucose in young adults (all ps < 0.05). Social support was associated with PA in both age groups as well as SB in younger youth. Auditory noises, lights, and safety inhibited sleep in both age groups. Conclusion: PA is critical for disease reduction, yet reducing SB and improving sleep are also important targets for reducing T2D risk in Hispanic adolescents and young adults. Future health promotion and disease prevention strategies should leverage qualitative findings regarding behavioral determinants.

The ectodysplasin receptor (EDAR) is a tumor necrosis factor receptor (TNF) superfamily member. A substitution in an exon of EDAR at position 370 (EDARV370A) creates a gain of function mutant present at high frequencies in Asian and Indigenous American populations but absent in others. Its frequency is intermediate in populations of Mexican ancestry. EDAR regulates the development of ectodermal tissues, including mammary ducts. Obesity and type 2 diabetes mellitus are prevalent in people with Indigenous and Latino ancestry. Latino patients also have altered prevalence and presentation of breast cancer. It is unknown whether EDARV370A might connect these phenomena. The goals of this study were to determine 1) whether EDARV370A is associated with metabolic phenotypes and 2) if there is altered breast anatomy in women carrying EDARV370A. Participants were from two Latino cohorts, the Arizona Insulin Resistance (AIR) registry and Sangre por Salud (SPS) biobank. The frequency of EDARV370A was 47% in the Latino cohorts. In the AIR registry, carriers of EDARV370A (GG homozygous) had significantly (p < 0.05) higher plasma triglycerides, VLDL, ALT, 2-hour post-challenge glucose, and a higher prevalence of prediabetes/diabetes. In a subset of the AIR registry, serum levels of ectodysplasin A2 (EDA-A2) also were associated with HbA1c and prediabetes (p < 0.05). For the SPS biobank, participants that were carriers of EDARV370A had lower breast density and higher HbA1c (both p < 0.05). The significant associations with measures of glycemia remained when the cohorts were combined. We conclude that EDARV370A is associated with characteristics of the metabolic syndrome and breast density in Latinos.

Alzheimer's disease (AD) affects Latinos disproportionately. One of the reasons underlying this disparity may be type 2 diabetes (T2D) that is a risk factor for AD. The purpose of this study was to examine the associations of T2D and AD blood biomarkers and the differences in these associations between Mexican Americans and non-Hispanic Whites. This study was a secondary analysis of baseline data from the observational Health and Aging Brain Study: Health Disparities (HABS-HD) that investigated factors underlying health disparities in AD in Mexican Americans in comparison to non-Hispanic Whites. HABS-HD participants were excluded if they had missing data or were large outliers (z-scores >|4|) on a given AD biomarker. Fasting blood glucose and glycosylated hemoglobin (HbA1c) levels were measured from clinical labs. T2D was diagnosed by licensed clinicians. Plasma amyloid-beta 42 and 40 (Aβ42/42) ratio, total tau (t-tau), and neurofilament light (NfL) were measured via ultra-sensitive Simoa assays. The sample sizes were 1,552 for Aβ42/40 ratio, 1,570 for t-tau, and 1,553 for NfL. Mexican Americans were younger (66.6±8.7 vs. 69.5±8.6) and had more female (64.9% female vs. 55.1%) and fewer years of schooling (9.5±4.6 vs. 15.6±2.5) than non-Hispanic Whites. Mexican Americans differed significantly from non-Hispanic Whites in blood glucose (113.5±36.6 vs. 99.2±17.0) and HbA1c (6.33±1.4 vs. 5.51±0.6) levels, T2D diagnosis (35.3% vs. 11.1%), as well as blood Aβ42/40 ratio (.051±.012 vs..047±.011), t-tau (2.56±.95 vs. 2.33±.90), and NfL levels (16.3±9.5 vs. 20.3±10.3). Blood glucose, blood HbA1c, and T2D diagnosis were not related to Aβ42/40 ratio and t-tau but explained 3.7% of the variation in NfL (p <.001). Blood glucose and T2D diagnosis were not, while HbA1c was positively (b = 2.31, p <.001, β = 0.26), associated with NfL among Mexican Americans. In contrast, blood glucose, HbA1c, and T2D diagnosis were negatively (b = -0.09, p <.01, β = -0.26), not (b = 0.34, p =.71, β = 0.04), and positively (b = 3.32, p <.01, β = 0.33) associated with NfL, respectively in non-Hispanic Whites. To conclude, blood glucose and HbA1c levels and T2D diagnosis are associated with plasma NfL levels, but not plasma Aβ and t-tau levels. These associations differ in an ethnicity-specific manner and need to be further studied as a potential mechanism underlying AD disparities. [ABSTRACT FROM AUTHOR]

Hydrocortisone stress dosing guidelines for children with adrenal insufficiency (AI) recommend a wide range of acceptable stress doses. This has led to variability in dosing recommendations resulting in confusion among endocrine, non-endocrine providers and patient families. This quality improvement project sought to standardize documentation and hydrocortisone stress dosing within our pediatric endocrine division to optimize communication regarding AI management. Plan-Do-Study-Act (PDSA) cycle one aimed to address documentation of components important in AI management including body surface area (BSA), home daily dose, home stress dose, in-patient stress dose, procedure dose and crisis dose using a smart phrase within the electronic health record (EHR). To automate the process, PDSA cycle two introduced two smart buttons within the endocrine notes. PDSA cycle three focused on standardizing hydrocortisone stress doses. Initial documentation targets were met for all AI management components except for the crisis dose. The second target was only met for the home stress dose. Implementing the smart buttons aided in reaching the second target for home daily and home stress doses. Dose standardization targets were achieved in all categories except for the on-going crisis dose. A follow up survey after an in-service for non-endocrine providers showed increased knowledge of locating hydrocortisone stress dosing recommendations within the EHR. With the assistance of technology, this quality improvement project ultimately enhanced communication through the standardization of documentation and individualized hydrocortisone stress dosing for children with AI. Although not all secondary targets were met, there was meaningful improvement in documentation and stress dose standardization compliance. [ABSTRACT FROM AUTHOR]

Background: We evaluated the 12-month effects of the COPE (Creating Opportunities for Personal Empowerment) Healthy Lifestyles TEEN (Thinking, Emotions, Exercise, Nutrition) program versus an attention control program (Healthy Teens) on overweight/obesity and depressive symptoms in high school adolescents. Methods: A cluster randomized controlled trial was conducted. Participants were 779 culturally diverse adolescents in the US Southwest. COPE is a cognitive-behavioral skills-building intervention with 20?min of physical activity integrated into a health course and taught by teachers once a week for 15 weeks. Outcome measures included body mass index (BMI) and depressive symptoms. Results: COPE teens had a significantly lower BMI at 12?months (F[subscript 1,698]?=?11.22, p?=?0.001) than Healthy Teens (24.95 versus 25.48). There was a significant decrease in the proportion of overweight and obese COPE teens from baseline to 12 months (?[superscript 2]?=?5.40, p?=?0.02) as compared with Healthy Teens. For youth who began the study with extremely elevated depressive symptoms, COPE teens had significantly lower depression at 12 months compared with Healthy Teens (COPE M?=?42.39; Healthy Teens M?=?57.90); (F[subscript 1,12]?=?5.78, p?=?0.03). Conclusions: COPE can improve long-term physical and mental health outcomes in teens.

The vitamin D receptor (VDR) is vital for maintaining calcium and phosphate balance and regulating bone metabolism. Recent research has suggested that VDR also plays an essential role in metabolic diseases. Previous studies on non-Hispanic whites have shown that VDR single nucleotide polymorphisms (SNP) are associated with cardiometabolic phenotypes. However, the association between VDR SNPs and cardiometabolic traits in Hispanics remains unclear. This study investigated the association between VDR SNPs and cardiometabolic phenotypic data in self-reported Hispanics (n = 1610) from the Arizona Insulin Resistance registry and Sangre Por Salud Biobank. The study population was predominantly female (66.4%) with a mean age of 40 ± 14 years (n = 121 <18 years) and an average body mass index (BMI) of 29.8 ± 6.3 kg/m2. We performed a genotyping association analysis of VDR SNPs (Taq1-rs731236, Fok1-rs2228570 and Apa1-rs7975232) with cardiometabolic traits using linear regression models. The results showed that Taq1 and Apa1 were strongly associated with systolic blood pressure (SBP) in children (<18 years), while Fok1 was associated with measures of adiposity, including fat mass, waist circumference, and BMI. In age-stratified adult (≥18 years) models, Taq1 was strongly associated with hemoglobin A1c, while Apa1 was associated with BMI and fasting glucose. Fok1 had no significant associations in the adult models. In conclusion, the VDR SNPs were associated with several cardiometabolic phenotypes in this Hispanic sample, but the type and strength of the associations varied by age group. [ABSTRACT FROM AUTHOR]