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1.  Physiological and Behavioral Stress and Anxiety in Children with Autism Spectrum Disorders during Routine Oral Care 
BioMed Research International  2014;2014:694876.
Background. Children with autism spectrum disorders (ASD) commonly exhibit uncooperative behaviors which impede oral care. Previous studies have utilized dentist-report measures of uncooperative behaviors in children with ASD but none have utilized an objective measure of children's behavior or a physiological measure of distress. This study investigated behavioral and physiological distress in children with ASD during routine oral care and examined factors associated with this distress. Methods. Participants were 44 children (n = 22 typical, n = 22 ASD) aged 6–12 receiving routine dental cleanings. Behavioral and physiological measures of stress and anxiety were collected during dental cleanings. Results. Children with ASD exhibited greater distress, compared to the typical group, on dentist-report and researcher-coded measures of overt distress behaviors and on physiological measures. Correlations between physiological and behavioral measures of distress were found in the ASD but not in the typical group. Behavioral distress was correlated with age in the typical group and with expressive communication ability and sensory processing difficulties in the ASD group; physiological distress was correlated with parent-report of anxiety in the typical group and sensory processing difficulties in the ASD group. Conclusions. Novel strategies may be required to decrease behavioral and physiological distress in children with ASD in the dental clinic.
PMCID: PMC4119730  PMID: 25114916
2.  Imagine HEALTH: results from a randomized pilot lifestyle intervention for obese Latino adolescents using Interactive Guided ImagerySM 
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.
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.
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.
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 Registry #: NCT01895595
PMCID: PMC3931490  PMID: 24433565
Guided imagery; Obesity; Childhood; Latino; Adolescents; Lifestyle; Diabetes
3.  Persistence of the metabolic syndrome and its influence on carotid artery intima media thickness in overweight Latino children 
Atherosclerosis  2009;206(2):594-598.
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.
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).
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).
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.
PMCID: PMC3767145  PMID: 19446812
CIMT; obesity; children; MetS
4.  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.
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.
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.
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.
PMCID: PMC3709847  PMID: 19555970
longitudinal; beta cell function; insulin sensitivity; insulin resistance; insulin IAUC
5.  Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE): a randomized controlled trial protocol 
BMC Neurology  2013;13:5.
Residual disability after stroke is substantial; 65% of patients at 6 months are unable to incorporate the impaired upper extremity into daily activities. Task-oriented training programs are rapidly being adopted into clinical practice. In the absence of any consensus on the essential elements or dose of task-specific training, an urgent need exists for a well-designed trial to determine the effectiveness of a specific multidimensional task-based program governed by a comprehensive set of evidence-based principles. The Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) Stroke Initiative is a parallel group, three-arm, single blind, superiority randomized controlled trial of a theoretically-defensible, upper extremity rehabilitation program provided in the outpatient setting.
The primary objective of ICARE is to determine if there is a greater improvement in arm and hand recovery one year after randomization in participants receiving a structured training program termed Accelerated Skill Acquisition Program (ASAP), compared to participants receiving usual and customary therapy of an equivalent dose (DEUCC). Two secondary objectives are to compare ASAP to a true (active monitoring only) usual and customary (UCC) therapy group and to compare DEUCC and UCC.
Following baseline assessment, participants are randomized by site, stratified for stroke duration and motor severity. 360 adults will be randomized, 14 to 106 days following ischemic or hemorrhagic stroke onset, with mild to moderate upper extremity impairment, recruited at sites in Atlanta, Los Angeles and Washington, D.C. The Wolf Motor Function Test (WMFT) time score is the primary outcome at 1 year post-randomization. The Stroke Impact Scale (SIS) hand domain is a secondary outcome measure.
The design includes concealed allocation during recruitment, screening and baseline, blinded outcome assessment and intention to treat analyses. Our primary hypothesis is that the improvement in log-transformed WMFT time will be greater for the ASAP than the DEUCC group. This pre-planned hypothesis will be tested at a significance level of 0.05.
ICARE will test whether ASAP is superior to the same number of hours of usual therapy. Pre-specified secondary analyses will test whether 30 hours of usual therapy is superior to current usual and customary therapy not controlled for dose.
Trial registration Identifier: NCT00871715
PMCID: PMC3547701  PMID: 23311856
Stroke; Brain infarction; Hemiparesis; Neurorehabilitation; Task-specific training; Motor recovery; Occupational therapy; Physical therapy
6.  Randomized Controlled Trial to Improve Adiposity, Inflammation, and Insulin Resistance in Obese African-American and Latino Youth 
Obesity (Silver Spring, Md.)  2011;20(4):811-818.
The purpose of this study was to examine ethnic differences in the metabolic responses to a 16-week intervention designed to improve insulin sensitivity (SI), adiposity, and inflammation in obese African-American and Latino adolescents. A total of 100 participants (African Americans: n = 48, Latino: n = 52; age: 15.4 ± 1.1 years, BMI percentile: 97.3 ± 3.3) were randomly assigned to interventions: control (C; n = 30), nutrition (N; n = 39, 1×/week focused on decreasing sugar and increasing fiber intake), or nutrition + strength training (N+ST; n = 31, 2×/week). The following were measured at pre- and postintervention: strength, dietary intake, body composition (dual-energy X-ray absorptiometry/magnetic resonance imaging) and glucose/insulin indexes (oral glucose tolerance test (OGTT)/intravenous glucose tolerance test (IVGTT)) and inflammatory markers. Overall, N compared to C and N+ST reported significant improvements in SI (+16.5% vs. −32.3% vs. −6.9% respectively, P < 0.01) and disposition index (DI: +15.5% vs. −14.2% vs. −13.7% respectively, P < 0.01). N+ST compared to C and N reported significant reductions in hepatic fat fraction (HFF: −27.3% vs. −4.3% vs. 0% respectively, P < 0.01). Compared to N, N+ST reported reductions in plasminogen activator inhibitor-1 (PAI-1) (−38.3% vs. +1.0%, P < 0.01) and resistin (−18.7% vs. +11.3%, P = 0.02). There were no intervention effects for all other measures of adiposity or inflammation. Significant intervention by ethnicity interactions were found for African Americans in the N group who reported increases in total fat mass, 2-h glucose and glucose incremental areas under the curve (IAUC) compared to Latinos (P’s < 0.05). These interventions yielded differential effects with N reporting favorable improvements in SI and DI and N+ST reporting marked reductions in HFF and inflammation. Both ethnic groups had significant improvements in metabolic health; however some improvements were not seen in African Americans.
PMCID: PMC3106142  PMID: 21293446
7.  Fasting Indicators of Insulin Sensitivity: Effects of Ethnicity and Pubertal Status 
Diabetes Care  2011;34(4):994-999.
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.
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.
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.
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.
PMCID: PMC3064063  PMID: 21357795
8.  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.
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.
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.
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.
PMCID: PMC3039101  PMID: 20888012
Insulin resistance; Beta cell function; puberty; longitudinal; Latino
9.  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.
PMCID: PMC3200494  PMID: 21436796
10.  Insulin Sensitivity as an Independent Predictor of Fat Mass Gain in Hispanic Adolescents 
Diabetes Care  2009;32(11):2114-2115.
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.
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.
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).
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.
PMCID: PMC2768217  PMID: 19675204
11.  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.
PMCID: PMC2882193  PMID: 18656576
12.  Randomized Control Trial to Improve Adiposity and Insulin Resistance in Overweight Latino Adolescents 
Obesity (Silver Spring, Md.)  2009;17(8):1542-1548.
Few randomized trials attempt to improve insulin sensitivity and associated metabolic risks in overweight Latino youth. The purpose of this study is to examine the effects of a modified carbohydrate nutrition program combined with strength training on insulin sensitivity, adiposity, and other type 2 diabetes risk factors in overweight Latino adolescents. In a 16-week randomized trial, 54 overweight Latino adolescents (15.5 ± 1.0 years) were randomly assigned to: (i) Control (C; n = 16), (ii) Nutrition (N; n = 21), or (iii) Nutrition + Strength training (N+ST; n = 17). The N group received modified carbohydrate nutrition classes (once per week), while the N+ST received the same nutrition classes plus strength training (twice per week). The following were measured at pre- and postintervention: strength by 1-repetition maximum, dietary intake by 3-day records, body composition by dual-energy X-ray absorptiometry, glucose/insulin indices by oral glucose tolerance test (OGTT) and intravenous glucose tolerance test with minimal modeling. Across intervention group effects were tested using analysis of covariance with post hoc pairwise comparisons. A significant overall intervention effect was found for improvement in bench press (P < 0.001) and reductions in energy (P = 0.05), carbohydrate (P = 0.04) and fat intake (P = 0.03). There were no significant intervention effects on insulin sensitivity, body composition, or most glucose/insulin indices with the exception of glucose incremental area under the curve (IAUC) (P = 0.05), which decreased in the N and N+ST group by 18 and 6.3% compared to a 32% increase in the C group. In conclusion, this intense, culturally tailored intervention resulted in no significant intervention effects on measured risk factors with the exception of a beneficial effect on glycemic response to oral glucose.
PMCID: PMC2846423  PMID: 19247280
13.  Aerobic and Strength Training Reduces Adiposity in Overweight Latina Adolescents 
To date, no study has examined the synergistic effects of a nutrition and combination of aerobic and strength training (CAST) on both adiposity and metabolic parameters in overweight Latina adolescent females. The goal was to assess if a 16-wk nutrition plus CAST pilot study had stronger effects on reducing adiposity and on improving glucose/insulin indices compared with control (C), nutrition only (N), and a nutrition plus strength training (N + ST) groups.
In a 16-wk randomized trial, 41 overweight Latina girls (15.2 ± 1.1 yr) were randomly assigned to C (n = 7), N (n = 10), N + ST (n = 9), or N + CAST (n = 15). All intervention groups received modified carbohydrate nutrition classes (once a week), whereas the N + ST also received strength training (twice a week) and the N + CAST received a combination of strength and aerobic training (twice a week). The following were measured before and after intervention: strength by one repetition maximum, physical activity by the 7-d accelerometry and the 3-d physical activity recall, dietary intake by 3-d records, body composition by dual-energy x-ray absorptiometry (DEXA), glucose/insulin indices by oral glucose tolerance test, and intravenous glucose tolerance test with minimal modeling. Across intervention group, effects were tested using ANCOVA with post hoc pairwise comparisons.
There were significant overall intervention effects for all adiposity measures (weight, body mass index [BMI], BMI z-scores, and DEXA total body fat), with a decrease of 3% in the N + CAST group compared with a 3% increase in the N + ST group (P ≤ 0.05). There was also an intervention effect for fasting glucose with the N group increasing by 3% and the N + CAST group decreasing by 4% (P ≤ 0.05).
The CAST was more effective than nutrition alone or nutrition plus strength training for reducing multiple adiposity outcomes and fasting glucose in overweight Latina girls. However, further research investigating and identifying intervention approaches that improve both adiposity and insulin indices, particularly in high-risk populations, are warranted.
PMCID: PMC2836768  PMID: 19516150
14.  Cardiorespiratory fitness predicts changes in adiposity in overweight Hispanic boys 
Obesity (Silver Spring, Md.)  2008;16(5):1072-1077.
We have previously shown that cardiorespiratory fitness predicts increasing fat mass during growth in white and African-American youth, but limited data are available examining this issue in Hispanic youth. Study participants were 160 (53% boys) overweight (BMI ≥ 85th percentile for age and gender) Hispanic children (mean ± SD age at baseline =11.2 ± 1.7 yrs). Cardiorespiratory fitness, or VO2max, was measured via a maximal effort treadmill test at baseline. Body composition by dual-energy x-ray absorptiometry and Tanner stage by clinical exam were measured at baseline and annually thereafter for up to four years. Linear mixed models were used to examine the gender specific relationship between VO2max and increases in adiposity (change in fat mass independent of change in lean tissue mass) over four years. The analysis was adjusted for changes in Tanner stage, age, and lean tissue mass. In boys, higher VO2max at baseline was inversely associated with the rate of increase in adiposity (β= -0.001, p=0.03); this effect translates to a 15% higher VO2max at baseline resulting in a 1.38kg lower fat mass gain over four years. However, VO2max was not significantly associated with changes in fat mass in girls (β=0.0002, p=0.31). In overweight Hispanic boys, greater cardiorespiratory fitness at baseline was protective against increasing adiposity. In girls however, initial cardiorespiratory fitness was not significantly associated with longitudinal changes in adiposity. These results suggest that fitness may be an important determinant of changes in adiposity in overweight Hispanic boys but not in girls.
PMCID: PMC2780237  PMID: 18309303
Children; Youth; Longitudinal; Gender

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