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1.  Blunted Nocturnal Cortisol Rise is Associated With Higher Carotid Artery Intima-Media Thickness (CIMT) in Overweight African American and Latino Youth 
Psychoneuroendocrinology  2013;38(9):1658-1667.
Background
Blunted diurnal cortisol variation has been associated with overt cardiovascular disease in adults. The relationship between the diurnal cortisol variation and subclinical atherosclerosis in youth has yet to be investigated. The objectives of this study were to: 1) determine the relationship between overnight cortisol measures and CIMT in overweight and obese, African-American and Latino children; 2) assess ethnic differences in these relationships and 3) explore whether overnight cortisol and CIMT relationships were independent of inflammatory markers, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).
Methods
One hundred and fifty-six overweight and obese African-American and Latino children (ages 8–17, 86M/70F, 55 African-American /101 Latino) underwent measures of CIMT by B-mode ultrasound, nocturnal cortisol rise (NCR=salivary cortisol rise from 2200hrs to awakening at 0530hrs), cortisol awakening response (CAR=salivary cortisol from time of awakening to 30 min later), fasting serum cortisol and overnight urinary free cortisol.
Results
Using linear regression, salivary cortisol0530hrs and NCR were negatively associated with CIMT (βstandardized = −0.215 and −0.220, p<0.01) independent of age, height, percent body fat, ethnicity and systolic blood pressure. Nocturnal salivary cortisol2200hrs, morning serum cortisol, and overnight urinary free cortisol were not associated with CIMT. Using ANCOVA, participants with LOW NCR (NCR <0.44µg/dL, n=52) had significantly greater CIMT than those with HIGH NCR (NCR ≥0.91 µg/dL, n=52; 0.632±0.008 vs. 0.603±0.008mm p=0.01) after controlling for covariates. Ethnicity was independently associated with CIMT, whereby African-American children had greater CIMT than Latino children (−0.028±0.009, p=0.006). The relationships between cortisol measures and CIMT did not differ between the two ethnic groups (all pinteraction=0.28–0.97). CRP, IL-6 and TNF-α were not associated with CIMT (p>0.05). IL-6 was inversely related to NCR (r=−0.186, p=0.03), but it did not explain the relationship between NCR and CIMT.
Conclusions
Salivary cortisol0530hrs and NCR, but not CAR, nocturnal salivary cortisol 2200hrs, morning serum cortisol or overnight urinary free cortisol, were associated with CIMT, independent of relevant covariates, including inflammatory factors. A low awakening salivary cortisol or a blunted NCR may be related to increased atherosclerosis risk in overweight and obese minority youth. These findings support adult studies suggesting flattened daytime diurnal cortisol variation impacts cardiovascular disease risk.
doi:10.1016/j.psyneuen.2013.01.011
PMCID: PMC3722251  PMID: 23433749
Obesity; cardiovascular risk; carotid artery; intima media thickness; cortisol
2.  Meal Skipping Linked to Increased Visceral Adipose Tissue and Triglycerides in Overweight Minority Youth 
Obesity (Silver Spring, Md.)  2013;22(5):E77-E84.
Objective
To investigate the impact of eating frequency on dietary intake, physical activity (PA), metabolic, and adiposity measures in minority youth.
Design and Methods
This analysis included 185 overweight (≥85th BMI percentile) Hispanic and African American youth (8–18 years) with the following cross-sectional measures: height, weight, BMI, dietary intake, body composition, metabolic parameters, PA, visceral adipose tissue (VAT), and subcutaneous adipose tissue. Each eating occasion (EO) was defined as ≥50 calories and ≥15 minutes from any previous EO. Participants were dichotomized based on EOs per 24-h into meal skippers <3 EO (MS; n=27) or normal/frequent eaters ≥3 EO (NFE; n=158). ANCOVAs were used to assess dietary intakes, metabolic outcomes, adiposity, and PA between eating frequency groups.
Results
MS compared to NFE consumed 24% fewer calories per 24-h (p≤0.01), 21% more calories per EO (p≤0.01), ate 40% less often (p≤0.01), had 18% higher triglycerides (p=0.03), and 26% more VAT (p=0.03), with no differences in PA.
Conclusions
Although meal skipping was associated with decreased energy intake, it was linked to increased calories per EO and higher triglycerides and VAT, which are strong indicators of deleterious metabolic profiles. These findings elucidate that meal skipping may be associated with increased VAT and related metabolic diseases in high-risk minority youth.
doi:10.1002/oby.20487
PMCID: PMC3759606  PMID: 23613461
Eating Behaviors; Life Styles; Minorities; Visceral Fat; Triglyceride
3.  Temporal Relationship Between Insulin Sensitivity and the Pubertal Decline in Physical Activity in Peripubertal Hispanic and African American Females 
Diabetes Care  2013;36(11):3739-3745.
OBJECTIVE
Little attention has been paid to possible intrinsic biological mechanisms for the decline in physical activity that occurs during puberty. This longitudinal observational study examined the association between baseline insulin sensitivity (SI) and declines in physical activity and increases in sedentary behavior in peripubertal minority females over a year.
RESEARCH DESIGN AND METHODS
Participants were Hispanic and African American girls (n = 55; 76% Hispanic; mean age 9.4 years; 36% obese). SI and other insulin indices were measured at baseline using the frequently sampled intravenous glucose tolerance test. Physical activity was measured on a quarterly basis by accelerometry and self-report.
RESULTS
Physical activity declined by 25% and time spent in sedentary behaviors increased by ∼13% over 1 year. Lower baseline SI predicted the decline in physical activity measured by accelerometry, whereas higher baseline acute insulin response to glucose predicted the decline in physical activity measured by self-report. Time spent in sedentary behavior increased by ~13% over 1 year, and this was predicted by lower baseline SI. All models controlled for adiposity, age, pubertal stage, and ethnicity.
CONCLUSIONS
When evaluated using a longitudinal design with strong outcome measures, this study suggests that lower baseline SI predicts a greater decline in physical activity in peripubertal minority females.
doi:10.2337/dc13-0083
PMCID: PMC3816891  PMID: 23846812
4.  Acculturation is Associated With Higher VO2max in Overweight Hispanic Children 
Pediatric exercise science  2006;18(1):89-100.
Acculturation has been implicated to be associated with physical activity (PA) behaviors in adults; little is known, however, with respect to the pediatric population. The purpose of this study was to determine whether cardiorespiratory fitness (VO2max) and/or PA were associated with acculturation status in overweight Hispanic children. In a sample of 144 children 8–13 years old, acculturation status was determined by place of birth: foreign born (n = 17), 1st generation (n = 101), or 2nd/3rd generation (n = 26), and by questionnaire: less assimilated (n = 76) or more assimilated (n = 34). VO2max was measured using a treadmill protocol, PA was assessed by questionnaire, and body composition by DEXA. ANOVA and ANCOVA were used to determine unadjusted and adjusted group differences, respectively. After adjusting for covariates, the 2nd/3rd generation group had significantly higher VO2max compared with the 1st generation group: 2.26 ± 0.20 L/min vs. 2.15 ± 0.19 L/min, p = .03. No differences were noted for PA, however. Acculturation to the U.S. is associated with higher VO2max in overweight Hispanic children. Longitudinal analyses are needed to determine whether these fitness differences confer protective health effects in this at-risk population.
PMCID: PMC4153401  PMID: 25197163
5.  Hemoglobin A1C above threshold levels are associated with decreased β-cell function in overweight Latino youth 
The Journal of Pediatrics  2011;160(5):751-756.
Objective
To determine, in an overweight pediatric population, if an A1C-determined high risk, pre-diabetic state (A1C ≥6.0–6.4%) is associated with decreased insulin sensitivity and β-cell dysfunction, known factors in the pathogenesis of type 2 diabetes.
Study design
We divided 206 healthy overweight Latino adolescents (124 male/82 female; age 13.1±2.0 yrs), into 2 groups: Lower Risk (LR, n=179) had A1C <6.0%; and High Risk (HR, n=27) had A1C 6.0–6.4%. Measures included A1C; OGTT fasting & 2-hr glucose and insulin; insulin sensitivity (SI), acute insulin response (AIR), and disposition index (DI, an index of β-cell function) by frequently sampled FSIVGTT with minimal modeling. Body fat was determined by DEXA.
Results
Compared with the LR group, the HR group had 21% lower SI (1.21±0.06 vs. 1.54±0.13, p<0.05), 30% lower AIR (928±102 vs. 1342±56, p<0.01), and 31% lower DI (1390±146 vs. 2023±83, p=0.001) after adjusting for age and total percent body fat.
Conclusion
These data provide clear evidence of greater impairment of β-cell function in those overweight Latino children with A1C 6.0–6.4%, and would thereby support the adoption of the International Expert Committee A1C-determined definition of high risk state for overweight children at risk for type 2 diabetes.
doi:10.1016/j.jpeds.2011.10.024
PMCID: PMC3297692  PMID: 22137671
Obesity; Prediabetes; A1c; beta cell function; insulin sensitivity
6.  Modifying Influence of Dietary Sugar in the Relationship Between Cortisol and Visceral Adipose Tissue in Minority Youth 
Obesity (Silver Spring, Md.)  2013;22(2):474-481.
Objective
Cortisol has been associated with preferential visceral adipose tissue (VAT) deposition; however findings in humans are mixed, which may be clarified when diet is considered.
Design and Methods
Participants included 165 African American and Latino, overweight adolescents (BMI% 97.2±3.2%, ages 13-18, 67% Latino, 66% female). Body composition was determined by DEXA, abdominal fat depots (VAT, subcutaneous (SAT)) by multiple-slice MRI, time-controlled serum sample to measure cortisol, and 2-day multi-pass 24-hour dietary recall. Linear regression analysis examined the cross-sectional relationship between cortisol, and the interaction of diet and cortisol on adiposity measures. Sex, race, age and total body fat were a priori covariates.
Results
There was a significant interaction between cortisol and sugar (total and added) in the prediction of VAT (pinteraction<=0.05). Amongst participants with high total or added-sugar intake, cortisol was significantly associated with VAT (β=0.031 p<0.001; β=0.026 p<0.001), with no relationship in low consumers of total or added-sugar.
Conclusion
Dietary sugar may play an important role in modifying the relationship between cortisol and VAT, such that cortisol is significantly associated with elevated VAT under conditions of high sugar intake.
doi:10.1002/oby.20594
PMCID: PMC3946447  PMID: 23929660
Adolescence; Cortisol; Omega-3 fatty acids; Sugar; visceral fat
7.  One-Hour Glucose During an Oral Glucose Challenge Prospectively Predicts β-Cell Deterioration and Prediabetes in Obese Hispanic Youth 
Diabetes Care  2013;36(6):1681-1686.
OBJECTIVE
In adults, 1-h glucose during an oral glucose tolerance test (OGTT) predicts the development of type 2 diabetes independent of fasting and 2-h glucose concentrations. The purpose of the current investigation was to examine the utility of elevated 1-h glucose levels to prospectively predict deterioration in β-cell function and the development of prediabetes in high-risk youth.
RESEARCH DESIGN AND METHODS
Obese Latino youth with a family history of type 2 diabetes (133 male and 100 female; age 11.1 ± 1.7 years) completed a baseline OGTT and were divided into two groups based upon a 1-h glucose threshold of 155 mg/dL (<155 mg/dL, n = 151, or ≥155 mg/dL, n = 82). Youth were followed annually for up to 8 years for assessment of glucose tolerance, body composition by dual-energy X-ray absorptiometry, and insulin sensitivity, insulin secretion, and the disposition index by the frequently sampled intravenous glucose tolerance test.
RESULTS
Over time, the ≥155 mg/dL group exhibited a significantly greater decline in β-cell function compared with youth with a 1-h glucose <155 mg/dL (β = −327.8 ± 126.2, P = 0.01). Moreover, this decline was independent of fasting or 2-h glucose and body composition. When the data were restricted to only participants with normal glucose tolerance at baseline, a 1-h glucose ≥155 mg/dL was independently associated with a 2.5 times greater likelihood of developing prediabetes during follow-up (95% CI 1.6–4.1, P = 0.0001).
CONCLUSIONS
These data suggest that a 1-h glucose ≥155 mg/dL during an OGTT is an independent predictor of β-cell deterioration and progression to prediabetes among obese Latino youth.
doi:10.2337/dc12-1861
PMCID: PMC3661793  PMID: 23315601
8.  Leptin predicts a decline in moderate to vigorous physical activity in minority female children at risk for obesity 
Pediatric obesity  2012;8(1):70-77.
Background
Leptin may influence moderate to vigorous physical activity (MVPA) at the start of puberty. The direction and magnitude of this association is unclear.
Objectives
To determine the effect of baseline leptin on MVPA over one year in minority girls at high-risk for obesity.
Methods
Data came from TRANSITIONS, a longitudinal observational study on the age-related MVPA decline. Fifty peri-pubertal girls aged 8–11 years at baseline participated. Baseline leptin (ng/mL) was collected via a duplicated assay using a double antibody Radio Immune Assay. MVPA (min/day) was measured using accelerometers for at least four 10-hr days on a quarterly basis for up to one year.
Results
Continuous leptin was negatively related to MVPA (p=0.001) independent of central adiposity at baseline and predicted the MVPA decline over one year (p=0.002). For descriptive purposes, baseline leptin was dichotomized at the sample median into ‘high leptin’ and ‘low leptin’ categories to determine whether MVPA trajectories differed between these groups. Girls with ‘low leptin’ at baseline had significantly higher levels of MPVA at baseline, visit 1, and visit 2 compared to girls with ‘high leptin’.
Conclusions
High leptin levels predicted nearly a 12.6% decline in MVPA over one year. These findings provide support for the biological basis of declining MVPA as girls enter puberty.
doi:10.1111/j.2047-6310.2012.00091.x
PMCID: PMC3527645  PMID: 22991241
leptin; accelerometer; biological basis; physical activity; adolescent
9.  Imagine HEALTH: results from a randomized pilot lifestyle intervention for obese Latino adolescents using Interactive Guided ImagerySM 
Background
There is an urgent need for innovative and developmentally appropriate lifestyle interventions to promote healthy lifestyle behaviors and to prevent the early onset of type 2 diabetes and cardiovascular disease risk in obese Latino adolescents. Guided imagery offers promise to reduce stress and promote lifestyle behavior change to reduce disease risk in obese adolescents. Our objectives were: 1) To pilot test a new 12-wk lifestyle intervention using a randomized trial design in obese Latino adolescents, in order to determine the effects of the mind-body modality of Interactive Guided ImagerySM (IGI), over and above those of a didactic lifestyle education, on insulin resistance, eating and physical activity behaviors, stress and stress biomarkers; and 2) To explore the role of intervention-related changes in stress and stress biomarkers on changes in metabolic outcomes, particularly insulin resistance.
Methods
Obese (BMI > 95th percentile), Latino adolescents (n = 35, age 14-17) were randomized to receive either 12 weekly sessions of a lifestyle education plus guided imagery program (GI), or lifestyle education plus a digital storytelling computer program (DS). Between-group differences in behavioral, biological, and psychological outcomes were assessed using unpaired T-tests and ANCOVA in the 29 subjects who completed the intervention.
Results
The GI group demonstrated significant reductions in leisure sedentary behavior (p < .05) and increases in moderate physical activity (p < .05) compared to DS group, and a trend toward reduced caloric intake in GI vs DS (p = .09). Salivary cortisol was acutely reduced by stress-reduction guided imagery (p < .01). There were no group differences in adiposity, insulin resistance, perceived stress, or stress biomarkers across the 12-week intervention, though decrease in serum cortisol over the course of the intervention was associated with improved insulin sensitivity (p = .03) independent of intervention group and other relevant co-variates.
Conclusions
The improvements in physical activity and stress biomarkers following this pilot intervention support the role of guided imagery in promoting healthy lifestyle behavior change and reducing metabolic disease risk in obese Latino adolescent populations. Future investigations will be needed to determine the full effects of the Imagine HEALTH intervention on insulin resistance, stress, and stress biomarkers.
Trial registration
Clinicaltrials.gov Registry #: NCT01895595
doi:10.1186/1472-6882-14-28
PMCID: PMC3931490  PMID: 24433565
Guided imagery; Obesity; Childhood; Latino; Adolescents; Lifestyle; Diabetes
10.  Acute Effects of Stress-Reduction Interactive Guided ImagerySM on Salivary Cortisol in Overweight Latino Adolescents 
Objectives
Chronic stress with relative hypercortisolism has been associated with metabolic disease risk. Stress-reduction interventions may therefore hold promise for reducing such chronic disease risk in obese youth. The purpose of this study was to conduct a 4-week pilot intervention to determine whether stress-reduction Interactive Guided ImagerySM (IGI) could serve as an acceptable and effective stress-reduction modality in over-weight Latino adolescents.
Design
Subjects (6 male/6 female, ages 14–17, body–mass index >95th percentile) were randomly assigned to the experimental guided imagery group (IGI, n = 6), or the nonintervention control group (C, n = 6). IGI subjects received four weekly 45-minute stress-reduction IGI sessions. Salivary cortisol was assessed immediately before and after each session. Acceptability was assessed by compliance and qualitative interviews.
Results
Subjects attended all sessions and expressed acceptance of the IGI intervention. There were significant within-group reductions in salivary cortisol in the IGI group in three of the four sessions, and no reductions in cortisol in the control group. For all four sessions combined, there was a significant between-group effect for the change in salivary cortisol in IGI versus C (p = 0.007). Effect sizes of cortisol change in IGI group were moderate to very high in the four sessions.
Conclusions
We conclude that IGI may be feasible and effective in acutely reducing salivary cortisol levels in overweight Latino adolescents. Future studies will need to determine whether stress-reduction IGI can result in longer-term reductions in chronic stress and measures of HPA activity.
doi:10.1089/acm.2008.0156
PMCID: PMC2838612  PMID: 19250005
11.  Acute Effects of Stress-Reduction Interactive Guided ImagerySM on Salivary Cortisol in Overweight Latino Adolescents 
Abstract
Objectives
Chronic stress with relative hypercortisolism has been associated with metabolic disease risk. Stress-reduction interventions may therefore hold promise for reducing such chronic disease risk in obese youth. The purpose of this study was to conduct a 4-week pilot intervention to determine whether stress-reduction Interactive Guided ImagerySM (IGI) could serve as an acceptable and effective stress-reduction modality in overweight Latino adolescents.
Design
Subjects (6 male/6 female, ages 14–17, body-mass index >95th percentile) were randomly assigned to the experimental guided imagery group (IGI, n = 6), or the nonintervention control group (C, n = 6). IGI subjects received four weekly 45-minute stress-reduction IGI sessions. Salivary cortisol was assessed immediately before and after each session. Acceptability was assessed by compliance and qualitative interviews.
Results
Subjects attended all sessions and expressed acceptance of the IGI intervention. There were significant within-group reductions in salivary cortisol in the IGI group in three of the four sessions, and no reductions in cortisol in the control group. For all four sessions combined, there was a significant between-group effect for the change in salivary cortisol in IGI versus C (p = 0.007). Effect sizes of cortisol change in IGI group were moderate to very high in the four sessions.
Conclusions
We conclude that IGI may be feasible and effective in acutely reducing salivary cortisol levels in overweight Latino adolescents. Future studies will need to determine whether stress-reduction IGI can result in longer-term reductions in chronic stress and measures of HPA activity.
doi:10.1089/acm.2008.0156
PMCID: PMC2838612  PMID: 19250005
12.  Persistence of the metabolic syndrome and its influence on carotid artery intima media thickness in overweight Latino children 
Atherosclerosis  2009;206(2):594-598.
Objective
The objective of this study was to examine the influence of persistence of the MetS (MetS) and its individual components over a 3-year period on carotid intima media thickness (CIMT) in overweight Latino children.
Methods
Ninety-seven healthy male and female overweight Latino children (mean age at baseline: 11.0±1.8 yrs) were assessed for MetS on four annual evaluations and classified according to the persistence of MetS: NEVER (0 annual visits with the MetS, n=53), INTERMITTENT (1 or 2 visits with the MetS, n=28), and PERSISTENT (3 or 4 visits with the MetS, n=16). CIMT was measured with high-resolution B-mode ultrasound (7.9±0.7 months after the most recent MetS assessment; mean age: 14.6±1.8 yr).
Results
PERSISTENT MetS was associated with significantly higher CIMT (0.647mm±0.018 compared to (0.600mm±0.007 in those who NEVER had MetS, p<0.01). This difference remained significant after controlling for gender, baseline age, total fat mass, total lean tissue mass and insulin sensitivity. PERSISTENT high waist circumference and PERSISTENT high blood pressure were also significantly associated with higher mean CIMT, but these differences were no longer significant after controlling for total fat and lean tissue mass. Baseline systolic blood pressure and 2-hour glucose were significantly related to CIMT independent of all other MetS components (p<0.05).
Conclusions
Persistence of the MetS over a 3-year period was uniquely associated with increased CIMT during childhood. Children with hypertension, persistent abdominal adiposity and impaired glucose tolerance may also be at higher risk for elevated CIMT.
doi:10.1016/j.atherosclerosis.2009.03.013
PMCID: PMC3767145  PMID: 19446812
CIMT; obesity; children; MetS
13.  Subclinical atherosclerosis in Latino youth: Progression of carotid intima media thickness (CIMT) and its relationship to cardiometabolic risk factors 
The Journal of pediatrics  2011;158(6):935-940.
Objective
To assess carotid artery intima media thickness (CIMT) change over two years in overweight Latino adolescents and examine its relationship to cardiometabolic risk.
Study design
72 healthy overweight male and female Latino adolescents (mean age: 14.5±1.7 yrs; mean BMI: 31.5±6.9 kg/m2) were evaluated at baseline and 2 years later for: CIMT by high resolution B-mode ultrasound, the metabolic syndrome and its features, body composition by DEXA and MRI, and glucose/insulin measures by fasting blood, and oral and intravenous glucose tolerance tests.
Results
Baseline CIMT did not differ from 2-year follow-up; however 38 participants increased CIMT (0.017±0.003mm; +2.8%) and 34 decreased (-0.019±0.002mm; −3.1%). ANCOVA analyses showed that participants with CIMT progression had higher baseline LDL-cholesterol and total cholesterol (91.3±3.4 and 150.3±3.9mg/dL) compared with those with CIMT regression (78.1±3.6 and 135.6±4.2mg/dL, p<0.05), independent of sex, baseline CIMT, age, and height. In multivariate regression, LDL-cholesterol was the sole predictor of CIMT progression, but the effect was small (odds of CIMT progression increased by 3% for each 1 mg/dL higher baseline LDL-cholesterol [95% CI: 1.004-1.006, p=0.03].
Conclusions
These results indicate a high variability in the magnitude of CIMT change in growing overweight Latino youth and support the use of LDL-cholesterol to assess sub-clinical atherosclerosis risk in this population.
doi:10.1016/j.jpeds.2010.12.008
PMCID: PMC3767153  PMID: 21238987
Obesity; Cardiovascular disease risk; Ultrasound imaging
14.  Adherence decision making in the everyday lives of emerging adults with type 1 diabetes 
Purpose
The purpose of this study was to explore motivations underlying nonadherent treatment decisions made by young adults with type 1 diabetes.
Methods
Eight emerging adults each completed a series of semi-structured interviews concerning their approaches to diabetes care, relationships with clinicians, and everyday activities and routines. A narrative thematic analysis was used to develop initial themes and refine them through continued data collection and review of the research literature.
Results
Five themes were identified as motivating nonadherence: (1) efforts to mislead health care providers, (2) adherence to alternative standards, (3) treatment fatigue and burnout, (4) social support problems, and (5) emotional and self-efficacy problems.
Conclusion
Instances of nonadherence generally involved a combination of the five identified themes. Participants reporting nonadherence also described difficulties communicating with care providers regarding their treatment. Nonjudgmental communication between providers and emerging adults may be particularly important in promoting positive health outcomes in this population.
doi:10.2147/PPA.S47577
PMCID: PMC3735338  PMID: 23935361
compliance; health behavior; nonadherence; motivations
15.  Persistence of the metabolic syndrome over 3 annual visits in overweight Latino children: Association with progressive risk for type 2 diabetes 
The Journal of pediatrics  2009;155(4):535-541.
Objective
To examine whether persistent Metabolic syndrome (MetS) was associated with risk for type 2 diabetes in overweight Latino children.
Study design
73 participants (age 11.0±1.7 years) from a longitudinal study were classified as: NEVER (negative for MetS at all 3 visits); INTERMITTENT (positive for MetS at 1 or 2 visits); or PERSISTENT (positive for MetS at all 3 visits). Measures included DEXA, MRI, 2-h oral glucose tolerance test, and frequently sampled intravenous glucose tolerance test.
Results
The PERSISTENT group had a faster rate of fat mass gain than the NEVER group (20% vs. 15% gain of baseline value, p<0.05 for time*group interaction (time= visit)). Independent of body composition, the PERSISTENT group increased by 70% in insulin incremental area under the curve, and the other groups decreased (p<0.05 for time*group interaction). Despite no time*group interactions for insulin sensitivity, acute insulin response, or disposition index, the PERSISTENT maintained 43% lower insulin sensitivity (p<0.01) and by visit 2 had a 25% lower disposition index (p<0.05) compared with the NEVER group.
Conclusion
Participants with persistent MetS had accelerated fat gain, increasing insulin response to oral glucose, and lower insulin sensitivity and beta cell function, indicators of progressively greater risk for type 2 diabetes.
doi:10.1016/j.jpeds.2009.04.008
PMCID: PMC3709847  PMID: 19555970
longitudinal; beta cell function; insulin sensitivity; insulin resistance; insulin IAUC
16.  Physical activity is related to insulin sensitivity in children and adolescents, independent of adiposity: a review of the literature 
In adults, there is evidence that physical activity effectively improves insulin sensitivity regardless of adiposity. Whether this is also the case in children and adolescents has been less clear. Whether this is also the case in children and adolescents is less clear. Clarifying this matter may help to identify the best outcomes to target in exercise programs for these age groups, where changes in adiposity may not always be desirable or realistic. A review of the literature was conducted on studies that examined the relationships of physical activity, cardiorespiratory fitness and strength with insulin sensitivity independent of adiposity in children and adolescents. Experimental (intervention) and correlational (longitudinal and cross-sectional) studies on participants ages 18 and younger were identified. A total of 42 studies were included in this review. Sample sizes in the studies ranged from 14 to 4,955 participants, with individual ages ranging from 5 to 19 years. A significant relationship with SI existed in 78% of studies on physical activity, 69% of studies on cardiorespiratory fitness and 66% of studies on strength. In studies that examined both physical activity and cardiorespiratory fitness concurrently, evidence suggests that they are both correlated with insulin sensitivity independent of adiposity, especially when physical activity is at higher intensities. However the strength of this relationship might be influenced by study design, measurement techniques and participant characteristics. This is the first review of its type to take research design into account, and to examine study outcomes according to participant ethnicity, gender, age, pubertal status and weight status.
doi:10.1002/dmrr.2292
PMCID: PMC3390444  PMID: 22389103
17.  Fasting Indicators of Insulin Sensitivity: Effects of Ethnicity and Pubertal Status 
Diabetes Care  2011;34(4):994-999.
OBJECTIVE
To examine the relationship of fasting indicators of insulin sensitivity with a more invasive measure of insulin sensitivity (frequently sampled intravenous glucose tolerance test [FSIVGTT]) and the effect of Tanner stage and ethnicity on that relationship.
RESEARCH DESIGN AND METHODS
Data were analyzed from 149 overweight girls (97 Hispanic and 52 African American) who were either in the early stages of maturation defined by Tanner stages 1 or 2 (52 Hispanic and 18 African American) or in the later stages of maturation defined by Tanner stages 4 and 5 (45 Hispanic and 34 African American). Fasting indicators of insulin sensitivity (IS) included fasting insulin and glucose and the homeostasis model assessment of insulin resistance (HOMA-IR). IS was derived from an FSIVGTT with minimal modeling.
RESULTS
In Tanner stages 1 and 2, all fasting indicators were significantly associated with IS: (fasting insulin: r = −0.67, P < 0.01; HOMA: r = −0.66, P < 0.01) with no significant influence of ethnicity on these relationships. In Tanner stages 4 and 5, however, all fasting indicators were associated with IS in African American girls (fasting insulin: r = −0.55, P < 0.01; HOMA: r = −0.47, P < 0.01), but none of the indicators were significantly associated with IS in Hispanic girls.
CONCLUSIONS
Fasting indicators were reflective of IS for girls in Tanner stages 1 and 2, regardless of ethnicity and may provide a clinical measure of future risk for type 2 diabetes. In the latter stages of maturation, however, more invasive measures are warranted to adequately determine IS in clinical practice.
doi:10.2337/dc10-1593
PMCID: PMC3064063  PMID: 21357795
18.  Pubertal Changes of Insulin Sensitivity, Acute Insulin Response and β-Cell function in Overweight Latino Youth 
The Journal of pediatrics  2011;158(3):442-446.
Objective
To examine changes in insulin sensitivity (SI), compensatory acute insulin response (AIR) and β-cell function/disposition index (DI) across puberty in overweight Latino boys and girls.
Study design
253 Latino children followed annually for up to 5 years. Longitudinal modeling was used to examine changes in SI, AIR, DI and fasting and 2-hr glucose and insulin across Tanner stage.
Results
In boys, SI decreased in early puberty with a recovery by late puberty. The compensatory increase in AIR was appropriate in early maturation, but after Tanner 3, AIR declined by more than that predicted from the recovery in SI. For girls, SI decreased in early puberty and across all stages of maturation. In early maturation, there was an appropriate compensatory increase in AIR, but after Tanner 3 AIR decreased. Thus, DI deteriorated across puberty in boys and girls.
Conclusions
In overweight Hispanic youth, compensatory changes in insulin secretion fails after Tanner 3 in both sexes, indicating β-cell deterioration during this critical period of development, thus increasing risk for Type 2 diabetes.
doi:10.1016/j.jpeds.2010.08.046
PMCID: PMC3039101  PMID: 20888012
Insulin resistance; Beta cell function; puberty; longitudinal; Latino
19.  CRP Is Related to Higher Leptin Levels in Minority Peripubertal Females Regardless of Adiposity Levels 
Obesity (Silver Spring, Md.)  2011;20(3):512-516.
Overweight is related to higher levels of C-reactive protein (CRP) and leptin, which have been independently associated with increased risk for diabetes, cardiovascular disease, and the metabolic syndrome. Elevated CRP may trigger leptin resistance by inhibiting the binding of leptin to its receptors. We cross-sectionally examined the relationship between CRP, leptin, BMI z-score, percent body fat (%BF) assessed by air plethysmography (BodPod), and insulin sensitivity (SI) and acute insulin response (AIRg) measured by intravenous glucose tolerance test in 51 Latina and African-American females (77% Latina), mean age 9.2 (±0.9) years, at either Tanner Pubertal Stage (TPS) 1 (n = 25) or TPS 2 (n = 26). Females at TPS 2 had higher BMI z-scores, %BF (23% ± 10.1 vs. 30% ± 10.0, P = 0.02), AIRg (976.7 ± 735.2 vs. 1555.3 ± 1,223 µIU/ml, P = 0.05), fasting insulin (11.0 ± 10.8 vs. 17.2 ± 13.6 µlU/ml, P = 0.00) and leptin levels (11.0 ± 7.1 vs. 19.6 ± 10.9 ng/ml, P < 0.001) than those at TPS 1. There were no ethnic differences in any of the measured variables. CRP was positively correlated with BMI z-score (P = 0.001), %BF (P = 0.006), fasting insulin and AIRg (P = 0.02), and fasting leptin (P = 0.00), and negatively correlated with SI (P = 0.05). A linear regression model showed that CRP independently explained 10% (P = 0.00) of the variance in leptin after adjusting %BF, TPS, ethnicity, habitual physical activity and SI. Hence, low-grade inflammation may contribute to prolonged leptin exposure and leptin resistance, even in healthy children.
doi:10.1038/oby.2011.49
PMCID: PMC3200494  PMID: 21436796
20.  Ethnic Differences in Pancreatic Fat Accumulation and Its Relationship With Other Fat Depots and Inflammatory Markers 
Diabetes Care  2011;34(2):485-490.
OBJECTIVE
Visceral adipose tissue (VAT) and hepatic fat are associated with insulin resistance and vary by sex and ethnicity. Recently, pancreatic fat fraction (PFF) has also been linked with increasing obesity. Our aim was to assess ethnic and sex differences in PFF and its relationship to other fat depots, circulating free fatty acids (FFA), insulin secretion and sensitivity, and inflammation in obese adolescents and young adults.
RESEARCH DESIGN AND METHODS
We examined 138 (40 males, 98 females) obese Hispanics and African Americans (13–25 years). Subcutaneous adipose tissue and VAT volumes, hepatic fat fraction (HFF), and PFF were determined by magnetic resonance imaging. Insulin sensitivity and β-cell function were assessed during an intravenous glucose tolerance test.
RESULTS
Hispanics had higher PFF than African Americans (7.3 ± 3.8 vs. 6.2 ± 2.6%, P = 0.03); this ethnic difference was higher in young adults compared with children and adolescents (ethnicity × age: P = 0.01). Males had higher PFF than females (P < 0.0001). PFF was positively correlated with VAT (r = 0.45, P < 0.0001), HFF (r = 0.29, P < 0.0001), and FFA (r = 0.32, P = 0.001). PFF positively correlated with inflammatory markers but lost significance when adjusted for VAT. In multiple stepwise regression analysis, VAT and FFA were the best predictors of PFF (adjusted R2 = 0.40). There were no significant correlations between PFF and markers of insulin sensitivity or β-cell function.
CONCLUSIONS
PFF is higher in Hispanics than African Americans, and this difference increases with age. In young obese individuals, PFF is related to VAT, HFF, and circulating FFA, thus possibly contributing to their increased risk for type 2 diabetes and related metabolic disorders.
doi:10.2337/dc10-0760
PMCID: PMC3024373  PMID: 21270204
21.  Effects of PNPLA3 on Liver Fat and Metabolic Profile in Hispanic Children and Adolescents 
Diabetes  2010;59(12):3127-3130.
OBJECTIVE
A genome-wide study of adults identified a variant of PNPLA3 (rs738409) associated with ∼twofold higher liver fat. The purpose of this study was to examine the influence of PNPLA3 genotype on liver fat and other related metabolic outcomes in obese Hispanic children and adolescents.
RESEARCH DESIGN AND METHODS
Three hundred and twenty-seven Hispanics aged 8–18 years were genotyped for rs738409. One hundred and eighty-eight subjects had measures of visceral (VAT) and subcutaneous (SAT) adipose tissue volume and hepatic (HFF) and pancreatic (PFF) fat fraction by magnetic resonance imaging. One hundred and thirty-nine subjects did not have HFF measures but had extensive measures of insulin sensitivity and fasting lipids.
RESULTS
Liver fat in GG subjects was 1.7 and 2.4 times higher than GC and CC (11.1 ± 0.8% in GG vs. 6.6 ± 0.7% in GC and 4.7 ± 0.9% in CC; P < 0.0001), and this effect was observed even in the youngest children (8–10 years of age). The variant was not associated with VAT, SAT, PFF, or insulin sensitivity or other glucose/insulin indexes. However, Hispanic children carrying the GG genotype had significantly lower HDL cholesterol (40.9 ± 10.9 in CC vs. 37.0 ± 8.3 in CG vs. 35.7 ± 7.4 in GG; P = 0.03) and a tendency toward lower free fatty acid levels (P = 0.06).
CONCLUSIONS
These results provide new evidence that the effect of the PNPLA3 variant is apparent in Hispanic children and adolescents, is unique to fat deposition in liver as compared with other ectopic depots examined, and is associated with lower HDL cholesterol.
doi:10.2337/db10-0554
PMCID: PMC2992774  PMID: 20852027
22.  Stress and abdominal Fat: Preliminary Evidence of Moderation by the Cortisol awakening Response in Hispanic Peripubertal Girls 
Obesity (Silver Spring, Md.)  2010;19(5):946-952.
Stress and the cortisol awakening response (CAR) have been independently linked to increases in abdominal fat depots. This cross-sectional study examined the CAR as a moderator of the association between stress, visceral adipose tissue (VAT), and subcutaneous abdominal adipose tissue (SAT) in a sample (N = 23) of female peripubertal Hispanic girls aged from 8 to 11. The study included: (i) monitored salivary cortisol collection, (ii) VAT and SAT obtained by multislice magnetic resonance imaging, and (iii) a stressful life events checklist with four domain-specific subscales: peer, family, personal, and school. Regression analysis indicated an interaction of school-related life events and CAR on VAT and SAT, with greater numbers of school-related events being related to greater VAT and SAT for girls with high CAR, but no association with VAT or SAT for girls with low CAR. Similar to job stress in adults, school-related stress in children may contribute to central adiposity, especially for girls with high CAR.
doi:10.1038/oby.2010.287
PMCID: PMC3107005  PMID: 21127479
23.  Relationships Between IGF-I and IGFBP-I and Adiposity in Obese African American and Latino Adolescents 
Obesity (Silver Spring, Md.)  2010;19(5):933-938.
The purpose of this study was to examine interrelationships between IGF-I, IGF binding proteins (IGFBPs), and adiposity in 49 African American and 77 Latino obese adolescents (15.3±0.1 and 15.4±0.2 yr; body mass index: 33.0±0.7 and 35.0±1.0 kg/m2, respectively). Immunoradiometric assays were used to measure IGF-I, IGFBP-I, and IGFBP-3. Total fat and soft lean tissue were measured by DEXA and visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and hepatic fat fraction (HFF) were measured by MRI. IGF-I levels were 23.1% higher and IGFBP-I were 40.4% higher in African Americans compared to Latinos after adjustment for total lean and total fat mass. IGF-I and IGFBP-I were inversely correlated with BMI, total fat mass, VAT, and HFF (r = −0.20 to −0.33, p<0.05) while IGFBP-I was inversely correlated with SAAT (r = −0.22, p<0.05). These relationships did not differ by ethnicity, however, the relationship between IGF-I and SAAT, as well as IGFBP-I and HFF, differed by ethnicity. Predicted mean IGF-I levels were 30.7% higher for African Americans at the 75th compared to 25th percentile of SAAT and only 11.7% higher for Latinos. Predicted mean IGFBP-I levels were 158% higher for African Americans at the 25th compared to the 75th percentile of HFF while IGFBP-I levels were 1.7% higher for Latinos at the 75th compared to the 25th percentile. These results demonstrate that the relationship between IGF-I and SAAT as well as IGFBP-I and HFF are different in African American and Latino adolescents and may contribute to the higher IGF-I levels in African Americans.
doi:10.1038/oby.2010.211
PMCID: PMC3081365  PMID: 20885383
Insulin-Like Growth Factors; Insulin-Like Growth Factor Binding Proteins; Ethnicity Differences; Obesity; Minorities
24.  Insulin Sensitivity as an Independent Predictor of Fat Mass Gain in Hispanic Adolescents 
Diabetes Care  2009;32(11):2114-2115.
OBJECTIVE
The purpose of this study was to examine the relationship between changes in insulin sensitivity and subsequent changes in fat mass in obese Hispanic children over 3 consecutive years.
RESEARCH DESIGN AND METHODS
In a longitudinal research design, insulin sensitivity (Si) of 96 research participants was determined at baseline and 1 year later. Body adiposity was assessed at four assessments.
RESULTS
The change in Si during the first year of the study was a significant predictor of further fat mass development (P < 0.05). Considering different directions of Si change, Si was a strong predictor for further fat mass development only in the group that decreased their Si (P < 0.05).
CONCLUSIONS
The results show that the direction of change in insulin sensitivity at an early age is an important independent predictor for further fat mass development and emphasize the importance of insulin sensitivity as a primary target for long-term obesity prevention, as well as the significance of early age intervention.
doi:10.2337/dc09-0833
PMCID: PMC2768217  PMID: 19675204
25.  Dietary Intake and the Metabolic Syndrome in Overweight Latino Children 
Little is known about the relationship between diet and metabolic health in Latino children, a population at increased risk for diabetes. The present study evaluates diet composition and the metabolic syndrome in a cross-sectional sample of 109 overweight Latino children aged 10 to 17 years with a family history of type 2 diabetes. Dietary intake was assessed by two 24-hour recalls. Associations between nutrients and features of the metabolic syndrome were examined using multiple linear regression and analysis of covariance. Log cholesterol intake was positively associated with log systolic blood pressure (β=0.034, P=0.017) and log soluble dietary fiber intake was inversely associated with log waist circumference (β=−0.069, P=0.036). Log soluble fiber intake was significantly higher in participants with 0 features compared to those with 3+ features of the metabolic syndrome (P=0.046), which translates to 5.2 g vs 4.1 g soluble fiber daily. No other significant associations were found between dietary variables and either the individual features of the metabolic syndrome or the clustering of metabolic syndrome components. Increases in soluble fiber through the daily consumption of fruits, vegetables, and beans may improve metabolic health in Latino children.
doi:10.1016/j.jada.2008.05.006
PMCID: PMC2882193  PMID: 18656576

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