The associations between type 2 diabetes and plasma biomarkers of Alzheimer's disease in the Health and Aging Brain Study: Health Disparities (HABS-HD).

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 (Aß42/42) ratio, total tau (t-tau), and neurofilament light (NfL) were measured via ultra-sensitive Simoa assays. The sample sizes were 1,552 for Aß42/40 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 Aß42/40 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 Aß42/40 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, ß = 0.26), associated with NfL among Mexican Americans. In contrast, blood glucose, HbA1c, and T2D diagnosis were negatively (b = -0.09, p < .01, ß = -0.26), not (b = 0.34, p = .71, ß = 0.04), and positively (b = 3.32, p < .01, ß = 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 Aß 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.

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.

Implementation of IT supported standardization of individualized hydrocortisone management for treatment of patients with adrenal insufficiency.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Association of Vitamin D Receptor Gene Polymorphisms with Cardiometabolic Phenotypes in Hispanics: A Life Course Approach.

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.

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.

Facilitating Growth Mixture Model Convergence in Preventive Interventions.

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.

A performance review of novel adiposity indices for assessing insulin resistance in a pediatric Latino population.

Introduction: Body mass index (BMI) percentile or BMI adjusted for age and sex is the most common anthropometric index to monitor and assess obesity in children. However, the ability of BMI to accurately predict insulin resistance (IR) in youth is debated. Determining the best method to noninvasively measure IR in the pediatric population is especially important due to the growing prevalence of type 2 diabetes mellitus (T2DM), which is more likely to develop in people with IR. Therefore, this study analyzed the performance of BMI against newer anthropometric indices in assessing IR in a pediatric Latino identifying sample. Methods: We studied 127 pediatric Latino participants from the Arizona Insulin Resistance (AIR) registry and performed linear regression analyses between various measures of IR and adiposity indices, including body mass index (BMI), triponderal mass index (TMI), body adiposity index (BAI), pediatric body adiposity index (pBAI), a body shape index (ABSI), abdominal volume index (AVI), waist to height ratio (WtHR) and waist to hip ratio (WHR). Log transformations of each index adjusted for age and sex and IR were used for the linear regressions. Additionally, we generated receiver operating characteristics (ROC) from logistic regressions between HOMA-IR and HOMA2IR against the same indices. Results: Using the homeostatic assessment of insulin resistance (HOMA-IR), HOMA2IR, the quantitative insulin-sensitivity check index (QUICKI), fasting serum insulin, and FPG/FSI to measure IR, we showed that BMI adjusted for age and sex performs similarly to many of the newer indices in our sample. The correlation coefficients for pBAI [R2: 0.27, 95% confidence interval: 0.88-1.81, p < 0.001] and BMI [R2: 0.27, 95% confidence interval: 0.92-1.92, p < 0.001] were the highest for HOMA-IR. Similarly, pBAI [R2: 0.29, 95% confidence interval: 0.88-1.72, p < 0.001] and BMI [R2: 0.29, 95% confidence interval: 0.93-1.83, p < 0.001] were the highest for HOMA2IR. A similar trend was observed with QUICKI, FSI, and FPG/FSI. ABSI had the lowest R 2 value for all measures of IR. Area under the curve (AUC) values for the receiver operating characteristics (ROC) for HOMA-IR and HOMA2IR support these conclusions. Conclusions: BMI adjusted for age and sex, despite its usage and simplicity, still stacks up well against newer indices in our Latino sample. Testing these indices across larger samples is necessary to generalize these findings and translate performance to adults.

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.

Feasibility, Acceptability, and Preliminary Efficacy of an Intensive Clinic-Based Intervention for Children With Poorly Controlled Type 1 Diabetes.

OBJECTIVE: To evaluate the feasibility, acceptability, and preliminary efficacy of a team-based intervention for youth with type 1 diabetes (T1D) with suboptimal glycemia, as detected based on the measurement of hemoglobin A1C (HbA1C). METHODS: Forty participants with T1D for >1 year and an HbA1C level of ≥9.5% (80 mmol/mol) enrolled for a multidisciplinary intervention that included pediatric endocrinologists, pediatric psychologists, and a certified diabetes care and education specialist (CDCES). The CDCES-integrated medical management, while reinforcing physical, emotional, and behavioral health, connected with families to set and monitor goals and reviewed medication adjustments. The feasibility was assessed based on enrollment targets; acceptability based on retention rates; and preliminary efficacy based on changes in HbA1C levels, quality of life, diabetes-related strengths and resilience, hospital admissions, emergency room visits, and missed school days. RESULTS: Of 43 patients and families approached, 40 agreed to participate, 36 completed the 4-month intervention, and 31 completed full 8 months of follow-up data collection. The CDCES coach averaged 6.8 contacts per participant during the 8-month study period. The HbA1C level reduced significantly from baseline to 4 months (12.1% ± 1.6% to 11.0% ± 1.9%, P = .001) and was sustained at 8 months (10.7% ± 1.9%, P < .001). The participants reported significant increases in diabetes-specific quality of life (P < .05) and diabetes-related strength and resilience (P = .003). The missed school days reduced from 7.23 ± 7.5 days to 1.55 ± 1.9 days (P < .001), and the diabetes-related hospitalizations decreased from 0.4 ± 0.6 to 0.1 ± 0.3 (P = .009). CONCLUSION: Preliminary data suggest that a multidisciplinary intervention leveraging a team-based approach with a physician, psychologist, and CDCES can support improvements in glycemic control and psychosocial outcomes among youth with T1D with an HbA1C level above the target.

Neighborhood Conditions and Type 2 Diabetes Risk among Latino Adolescents with Obesity in Phoenix.

Type 2 Diabetes (T2D) has reached epidemic levels among the pediatric population. Furthermore, disparities in T2D among youth are distributed in a manner that reflects the social inequality between population sub-groups. Here, we investigated the neighborhood determinants of T2D risk among a sample of Latino adolescents with obesity residing in Phoenix, Arizona (n = 133). In doing so we linked together four separate contextual data sources: the American Community Survey, the United States Department of Agriculture Food Access Research Atlas, the Arizona Healthy Community Map, and the National Neighborhood Data Archive to systematically analyze how and which neighborhood characteristics were associated with T2D risk factors as measured by fasting and 2-h glucose following a 75 g oral glucose tolerance test. Using linear regression models with and without individual/household covariates, we investigated how twenty-two housing and transportation sociodemographic and built and food environment characteristics were independently and jointly associated with T2D risk. The main finding from these analyses was the strong association between the density of fast food restaurants and 2-h glucose values (b = 2.42, p < 0.01). This association was independent of individual, household, and other neighborhood characteristics. Our results contribute to an increasingly robust literature demonstrating the deleterious influence of the neighborhood food environment, especially fast food, for T2D risk among Latino youth.

Sustainability via Active Garden Education: The Sustainability Action Plan Model and Process.

Sustainability of intervention programming is challenging to achieve under real world conditions, since few models exist and many studies do not plan far beyond the funding period. Programming content in early care and education centers (ECECs) is often driven by guidelines. However, implementation is very sensitive to contextual factors, such as the setting and implementer (teacher) characteristics. This paper presents the model, definitions, and methodology used for the sustainability action plan capitalizing on a community-based participatory research (CBPR) approach, developed for a multi-site, multi-level garden-based childhood obesity prevention study, Sustainability via Active Garden Education (SAGE). The Ecologic Model of Obesity is applied to develop a sustainability action plan (SAP) and accompanying measures to link early care and education (ECE) environment, the community, policies, and classroom practices to an early childhood obesity prevention program. The SAGE SAP provides an example of how to iteratively evaluate and refine sustainability processes for an obesity prevention intervention utilizing CBPR approaches and will be applied to assess the sustainability of SAGE in a cluster randomized controlled trial. This SAP model can also help inform intervention delivery and scalability within ECECs.

Early Care and Education Center Environmental Factors Associated with Product- and Process-Based Locomotor Outcomes in Preschool-Age Children.

Environmental characteristics of early care and education centers (ECECs) are an important context for preschool-aged children's development, but few studies have examined their relationship with children's locomotor skills. We examined the association between characteristics of the ECEC environment with quantitatively (i.e., product-based) and qualitatively (i.e., process-based) measured locomotor skills, using the Progressive Aerobic Cardiovascular Endurance Run (PACER) and the locomotor portion of the Children's Activity and Movement in Preschool Study (CHAMPS) motor skills protocol (CMSP), respectively. ECEC characteristics included outdoor and indoor play environment quality, outdoor and indoor play equipment, screen-time environment quality, and policy environment quality. Mean (SD) scores for the PACER (n = 142) and CSMP (n = 91) were 3.7 ± 2.3 laps and 19.0 ± 5.5 criteria, respectively, which were moderately correlated with each other (Pearson r = 0.5; p < 0.001). Linear regression models revelated that a better policy environment score was associated with fewer PACER laps. Better outdoor play and screen-time environment quality scores and more outdoor play equipment were positively associated with higher CMSP scores. ECEC environments that reflect best practice guidelines may be opportunities for locomotor skills development in preschool-aged children. ClinicalTrials.gov Identifier: NCT03261492 (8/25/17).

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.

Examining 24-Hour Activity and Sleep Behaviors and Related Determinants in Latino Adolescents and Young Adults With Obesity.

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 (≥10 hours/day). Sleep regularity was negatively associated with adiposity (all ps < .05) in both age groups as well as fasting and 2-hour glucose in young adults (all ps < .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.

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.

Feasibility and Acceptability of a Type 2 Diabetes Prevention Intervention for Mothers and Children at a Federally Qualified Healthcare Center.

BACKGROUND: Maternal obesity and gestational diabetes mellitus (GDM) contribute to increased risk for type 2 diabetes mellitus (T2DM) among both mothers and their offspring. Randomized trials demonstrated T2DM risk reduction in adults following lifestyle behavior change and modest weight loss; the evidence base for at-risk children remains limited. PURPOSE: Evaluate the feasibility, acceptability, and preliminary efficacy of a T2DM prevention intervention for mother-child dyads delivered by Federally Qualified Health Center staff. METHODS: A group randomized design tested the effects of a behavioral lifestyle intervention on T2DM risk factors in women with a history of GDM and their 8- to 12-year-old children. Mother-child dyads were recruited and randomized to intervention or wait-listed control conditions. Intervention participants completed the 13-week intervention; control participants received standard of care. Baseline and 13-week measures assessed program acceptability and feasibility, and explored effects on body weight, waist circumference, hemoglobin A1c, and lifestyle behaviors. RESULTS: Forty-two dyads were randomized and 35 (83%) completed pre-/post-measurements. Participants and program leaders positively rated content and engagement. Nearly all strongly agreed that activities were enjoyable (97%), applicable (96%), useful (97%), and motivational (96%). Attendance averaged 65% across 2 cohorts; delivery costs were approximately $225/dyad. There were no significant differences in body weight, BMI (or BMI z-score), waist circumference, hemoglobin A1c, diet quality, physical activity, sleep, or home environment changes between intervention and control groups. CONCLUSIONS: A family T2DM prevention program was feasibly delivered by FQHC staff, and acceptable to mothers and children. Program efficacy will be evaluated in an adequately powered clinical trial.

Association of EDARV370A with breast density and metabolic syndrome in Latinos.

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.