Prediabetes in Adolescents: Prevalence, Management and Diabetes Prevention Strategies.

The ongoing obesity epidemic in children and adolescents has greatly increased the prevalence of related comorbidities. Prediabetes is defined based on levels of fasting glucose, oral glucose tolerance tests or hemoglobin A1c, that are intermediate between normal levels and thresholds that define type 2 diabetes mellitus (T2DM). As such, prediabetes represents a sign of early pathophysiology preceding T2DM development. Recent analyses of data from US adolescents estimate prediabetes to be present in 4-23% of adolescents, depending on criteria used, with other studies finding an 8% risk of progression from prediabetes to T2DM over a 3-year period. These data support the importance of intervention to avoid long-term sequelae, focusing on reducing degree of obesity and insulin resistance. Lifestyle modification, with increases in physical activity and dietary improvements, remains the first-line approach. Other interventions are based on additional long-term risks and range from metformin treatment for more moderate cases of prediabetes to bariatric surgery for adolescents with severe obesity and comorbidities. As data accumulate regarding sequelae of T2DM in adolescents, there remains a critical need for prevention of obesity and T2DM throughout childhood, and prediabetes should be a trigger for improving this risk profile.

Benefits of Airway Androgen Receptor Expression in Human Asthma.

Rationale: Androgens are potentially beneficial in asthma, but AR (androgen receptor) has not been studied in human airways.Objectives: To measure whether AR and its ligands are associated with human asthma outcomes.Methods: We compared the effects of AR expression on lung function, symptom scores, and fractional exhaled nitric oxide (FeNO) in adults enrolled in SARP (Severe Asthma Research Program). The impact of sex and of androgens on asthma outcomes was also evaluated in the SARP with validation studies in the Cleveland Clinic Health System and the NHANES (U.S. National Health and Nutrition Examination Survey).Measurements and Main Results: In SARP (n = 128), AR gene expression from bronchoscopic epithelial brushings was positively associated with both FEV1/FVC ratio (R2 = 0.135, P = 0.0002) and the total Asthma Quality of Life Questionnaire score (R2 = 0.056, P = 0.016) and was negatively associated with FeNO (R2 = 0.178, P = 9.8 × 10-6) and NOS2 (nitric oxide synthase gene) expression (R2 = 0.281, P = 1.2 × 10-10). In SARP (n = 1,659), the Cleveland Clinic Health System (n = 32,527), and the NHANES (n = 2,629), women had more asthma exacerbations and emergency department visits than men. The levels of the AR ligand precursor dehydroepiandrosterone sulfate correlated positively with the FEV1 in both women and men.Conclusions: Higher bronchial AR expression and higher androgen levels are associated with better lung function, fewer symptoms, and a lower FeNO in human asthma. The role of androgens should be considered in asthma management.

Use of metabolic syndrome severity to assess treatment with vitamin E and pioglitazone for non-alcoholic steatohepatitis.

BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH), which can lead to liver failure, requires liver biopsies to follow and is difficult to treat. Our goal was to assess metabolic syndrome (MetS) severity as a predictor of treatment success and a marker of response. METHODS: We assessed data from the Pioglitazone, Vitamin E, or Placebo for NASH Study, in which individuals with biopsy-confirmed NASH were randomized to receive pioglitazone, vitamin E, or placebo for 96 weeks. We assessed associations of a sex-specific and race/ethnicity-specific MetS severity Z-score (MetS-Z) at baseline and 48 weeks with biopsy-determined endpoint of NASH resolution at 96 weeks. RESULTS: Baseline MetS-Z was inversely associated with odds of NASH resolution (odds ratio [OR] per 1 SD of MetS-Z: 0.47, 95% confidence interval [CI] 0.28, 0.79). Decrease in MetS-Z during initial 48-week intervention was greatest for pioglitazone treatment (effect size: -0.31, 95% CI -0.15, -0.48) and for vitamin E tended toward being greater for those with versus without NASH resolution (-0.18 vs -0.05). Overall, 48-week change in MetS-Z was associated with NASH resolution (OR per 1-SD change: 0.53, 95% CI 0.33, 0.85), although this was attenuated in models that included transaminases, which remained linked to treatment success (OR by change-in-aspartate aminotransferase Z-score: 0.38, 95% CI 0.19, 0.76). CONCLUSIONS: Individuals with more severe metabolic derangement at baseline were less likely to exhibit NASH resolution, suggesting that individuals may have a threshold of MetS severity beyond which successful treatment is unlikely. As an integrated marker of metabolic abnormalities, MetS-Z was correlated with successful treatment, although transaminases were a more consistent marker of NASH resolution.

Objective and subjective socioeconomic status associated with metabolic syndrome severity among African American adults in Jackson Heart Study.

PURPOSE: To assess independent associations between objective socioeconomic status (OSS) and subjective social status (SSS) with metabolic syndrome (MetS) severity and indicators among African American (AA) adults in the Jackson Heart Study (JHS) at baseline (2000-2004) and eight-year follow-up (2009-2013). METHODS: Participants included 1724 AA adults from the JHS cohort (64.4 % women; mean age 53.4 ± 11.8). Associations of OSS (annual household income and school years completed) and SSS (measured with MacArthur Scales) with sex- and race/ethnic-specific MetS severity Z-score were examined after adjustment for demographics and MetS risk factors (i.e., nutrition, physical activity, smoking status, alcohol consumption, and depressive symptoms) at baseline and eight-year follow-up. PRINCIPAL RESULTS: Independent of OSS, demographic, psychosocial, and lifestyle factors, individuals with lower US-society SSS had more severe MetS at baseline. A significant interaction existed between sex and US-society SSS such that women with lower perceived social status had more severe MetS severity at baseline, and for every one unit increase in US-society SSS, MetS severity Z-score is estimated to decrease by 0.04. Components of MetS driving the relationship between US-society SSS and MetS severity at baseline were the inverse associations of SSS with glucose levels and the positive associations of SSS with HDL-C. Physical activity was independently associated with MetS severity at baseline, but not at eight-year follow-up. MAJOR CONCLUSIONS: Though subjective and objective measures of social status are independently associated with cardiometabolic risk factors and MetS severity among AA adults, SSS may be a stronger predictor of MetS severity than OSS, particularly among women. SSS should be considered in conjunction with OSS when exploring social determinants of cardiometabolic health.

Associations of a metabolic syndrome severity score with coronary heart disease and diabetes in fasting vs. non-fasting individuals.

BACKGROUND AND AIMS: Many traditional assessments of risk for coronary heart disease (CHD) and diabetes require laboratory studies performed after an 8-h fast. We assessed whether metabolic-syndrome (MetS) severity would remain linked to future CHD and diabetes even when assessed from non-fasting samples. METHODS AND RESULTS: Participants in the Atherosclerosis Risk in Communities study were assessed at 4 visits and followed for 20-years of adjudicated CHD outcomes. We used Cox proportional-hazard models (for 20-year CHD outcomes) and logistic regression (for 9-year diabetes outcomes) to compare incident disease risk associated with a race/ethnicity-specific MetS-severity Z-score (MetS-Z) calculated in participants who were fasting (≥8 h) or non-fasting. All analyses were adjusted for sex, race, education, income and smoking. MetS Z-scores were overall similar between participants who were always fasting vs. those non-fasting at Visits 1-3 (all values -0.1 to 0.4), while MetS-Z for participants who were non-fasting at Visit-4 were higher at each visit. Baseline MetS-Z was linked to future CHD when calculated from both fasting and non-fasting measurements, with hazard ratio (HR) for fasting MetS-Z 1.53 (95% confidence interval [CI] 1.42, 1.66) and for non-fasting 1.28 (CI 1.08, 1.51). MetS-Z at Visit-1 also remained linked to future diabetes when measured from non-fasting samples, with odds ratio for fasting MetS-Z 3.10 (CI 2.88, 3.35) and for non-fasting 1.92 (CI 1.05, 3.51). CONCLUSIONS: MetS-Z remained linked to future CHD and diabetes when assessed from non-fasting samples. A score such as this may allow for identification of at-risk individuals and serve as a motivation toward interventions to reduce risk.

Dehydroepiandrosterone Supplementation May Benefit Women with Asthma Who Have Low Androgen Levels: A Pilot Study.

INTRODUCTION: Among individuals with severe asthma, FEV1 is low in individuals with low dehydroepiandrosterone (DHEA) sulfate (DHEAS) levels. In the Severe Asthma Research Program (SARP), no women with DHEAS > 200 µg/dL had an FEV1 < 60% predicted. DHEA has benefited patients with COPD and pulmonary hypertension in small trials. Therefore, we hypothesized that DHEA supplementation may improve FEV1 in asthmatic women with low DHEAS. METHODS: Premenopausal, nonsmoking, otherwise healthy women, 18-50 years old, with mild or moderate asthma and baseline FEV1 > 60% predicted received 100 mg DHEA orally every 12 h for 2 weeks. Spirometry and DHEAS were measured at the initial visit and 2 weeks later, after completion of DHEA treatment. Based on our previous work, the primary outcome variable for this pilot study was post-albuterol spirometry in the low-DHEAS group. Subjects also continued their other routine asthma management. RESULTS: Serum DHEAS increased with DHEA treatment in women with starting DHEAS < 200 µg/dL: this increase was from 71 ± 23 to 725 ± 295 µg/dL (n = 10; p = 0.0001). The increase in the high-DHEAS group was smaller. Post-albuterol FEV1 increased by 51 mL, from 3.026 ± 0.5 to 3.077 ± 0.49 L (n = 10; p = 0.034 by paired t test, significant after Bonferroni), in women with low DHEAS. In the high-DHEAS group (baseline DHEAS ≥ 200 µg/dl), post-albuterol FEV1 did not change significantly (n = 3, p = NS). Three subjects were excluded: one had comorbid COPD, one could not perform spirometry, and one did not take the DHEA. There were no adverse effects of DHEA treatment in this trial. CONCLUSIONS: Endocrine treatments (corticosteroids) are a mainstay of anti-inflammatory management for moderate and severe asthma. Their use has improved asthma outcomes. Androgens also reduce airway inflammation and promote airway smooth muscle relaxation, but are rarely used clinically for asthma treatment. Our results suggest that the over-the-counter steroid DHEA may improve lung function in asthma outcomes among women with DHEAS < 200 ug/dL.

Metabolic syndrome severity and lifestyle factors among adolescents.

The continued rise of pediatric obesity globally has raised concerns for related sequalae. One marker of risk is the metabolic syndrome, a cluster of cardiovascular risk factors that is associated with future cardiovascular disease and type 2 diabetes. MetS has at its core visceral adipocytes exhibiting dysfunction as a result of excess fat content. MetS in children and adolescents is linked to unhealthy lifestyle practices such as sedentary lifestyles and excess consumption calories. As such, the optimal means of addressing MetS is targeting a decrease in adiposity through lifestyle modification, a decrease in MetS following increases in physical activity and improvements in the quality and content of food intake. Efforts remain needed in increasing motivation to these changes and maintaining adherence to avoid long-term sequelae.

Association of psychosocial stressors with metabolic syndrome severity among African Americans in the Jackson Heart Study.

INTRODUCTION: Using Jackson Heart Study (JHS) data, we assessed the association between perceived psychosocial stressors and metabolic syndrome (MetS) severity in African American adults. METHODS: Participants included 3870 African American JHS participants aged 21-95 years (63.1% women; mean age 53.8 ±â€¯13.0). Psychosocial stressors assessed included: major life events (MLEs); global stress; and weekly stress inventory. Each stress measure was classified into tertiles (low, medium, and high). Associations of psychosocial stressors with a sex- and race/ethnic-specific MetS severity Z-score were examined after adjustment for demographics and MetS risk factors (i.e., nutrition, physical activity, smoking status, and alcohol consumption). RESULTS: Independent of lifestyle factors, participants who reported high (versus low) perceived global stress and MLEs had significantly greater MetS severity (p = .0207 and p = .0105, respectively). Weekly stress was not associated with MetS severity. Compared to men, women reported significantly higher global stress and MLEs (p < 0.0001). A significant interaction between sex and MLEs (p = .0456) demonstrated men significantly increased their MetS severity at medium levels of stress, whereas women's MetS severity was significantly increased at high levels of MLEs. CONCLUSIONS: In the total sample, higher reported global stress and MLEs were associated with increased risk of MetS severity, while weekly stress was not. Men's and women's stress responses to MLEs were differentially associated with MetS severity, with male MetS severity increasing significantly at lower levels of MLEs relative to women's MetS severity. These data may have implications for targeting stress-related factors in interventions to improve cardiometabolic health in African American adults.

Increases in IGF-1 After Anti-TNF-α Therapy Are Associated With Bone and Muscle Accrual in Pediatric Crohn Disease.

Context: Low levels of insulinlike growth factor 1 (IGF-1) in pediatric and adolescent Crohn disease (CD) likely contribute to bone and muscle deficits. Objective: Assess changes in IGF-1 levels and associations with bone and muscle accrual following initiation of anti-tumor necrosis factor α (TNF-α) therapy in pediatric and adolescent CD. Design and Participants: Participants (n = 75, age 5 to 21 years) with CD were enrolled in a prospective cohort study; 63 completed the 12-month visit. Main Outcome Measures: IGF-1 levels at baseline and 10 weeks, as well as dual-energy x-ray absorptiometry (DXA) and tibia peripheral quantitative computed tomography (pQCT) measures of bone and muscle at baseline and 12 months after initiation of anti-TNF-α therapy. Outcomes were expressed as sex-specific z scores. Results: IGF-1 z scores increased from a median (interquartile range) of -1.0 (-1.58 to -0.17) to -0.36 (-1.04 to 0.36) over 10 weeks (P < 0.001). Lesser disease severity and systemic inflammation, as well as greater estradiol z scores (in girls), was significantly associated with greater IGF-1 z scores over time. DXA whole-body bone mineral content, leg lean mass, and total hip and femoral neck bone mineral density (BMD) z scores were low at baseline (P < 0.0001 vs reference data) and increased significantly (P < 0.001) over 12 months. Greater increases in IGF-1 z scores over 10 weeks predicted improvement in DXA bone and muscle outcomes and pQCT trabecular BMD and cortical area. Adjustment for changes in muscle mass markedly attenuated the associations between IGF-1 levels and bone outcomes. Conclusions: Short-term improvements in IGF-1 z scores predicted recovery of bone and muscle outcomes following initiation of anti-TNF-α therapy in pediatric CD. These data suggest that disease effects on growth hormone metabolism contribute to musculoskeletal deficits in CD.

Mice with infectious colitis exhibit linear growth failure and subsequent catch-up growth related to systemic inflammation and IGF-1.

In developing communities, intestinal infection is associated with poor weight gain and linear-growth failure. Prior translational animal models have focused on weight gain investigations into key contributors to linear growth failure have been lacking. We hypothesized that murine intestinal infection with Citrobacter rodentium would induce linear-growth failure associated with systemic inflammation and suppressed serum levels of insulin-like growth factor-1 (IGF-1). We evaluated 4 groups of mice infected or sham-infected on day-of-life 28: uninfected-controls, wild-type C rodentium-infected, partially-attenuated C rodentium-infected (with deletion of 3 serine protease genes involved in colonization), and pair-fed (given the amount of daily food consumed by the wild-type C rodentium group). Relative to the uninfected group, mice infected with wild-type C rodentium exhibited temporal associations of lower food intake, weight loss, linear-growth failure, higher IL-6 and TNF-α and lower IGF-1. However, relative to the pair-fed group, the C rodentium-infected group only differed significantly by linear growth and systemic inflammatory cytokines. Between post-infection days 15-20, the infected group exhibited resolution of systemic inflammation. Between days 16-20, both wild-type C rodentium and pair-fed groups exhibited rapid linear-growth velocities exceeding the uninfected and mutant C rodentium groups; during this time levels of IGF-1 increased to match the uninfected group. We submit this as a model providing important opportunities to study mechanisms of catch-up growth related to intestinal inflammation. We conclude that in addition to known effects of weight loss, infection with C rodentium induces linear-growth failure potentially related to systemic inflammation and low levels of IGF-1, with catch-up of linear growth following resolution of inflammation.

Trends in Metabolic Syndrome Severity and Lifestyle Factors Among Adolescents.

BACKGROUND AND OBJECTIVES: Childhood metabolic syndrome (MetS) is a risk factor for adverse outcomes later in life. Our goal was to identify temporal trends among US adolescents in the severity of MetS, its individual components, and factors related to diet and physical activity. METHODS: We analyzed 5117 participants aged 12 to 19 from NHANES. We used regression analysis of individual waves of data, 1999 to 2012. MetS severity was calculated using a gender- and race/ethnicity-specific MetS severity z score. RESULTS: There was a linear trend of decreasing MetS severity in US adolescents from 1999 to 2012 (P = .030). This occurred despite a trend of increasing BMI z score (P = .005); instead, the decrease in MetS severity appeared to be due to trends in increasing high-density lipoprotein (HDL; P < .0001) and decreasing triglyceride (P = .0001) levels. In considering lifestyle factors, there was no change in physical activity over the time period. Regarding dietary patterns, total calorie consumption and carbohydrate consumption were positively associated with triglyceride levels and negatively associated with HDL levels, whereas unsaturated fat consumption exhibited the opposite associations. Consistent with these associations, there was a trend of decreasing total calorie consumption (P < .0001), decreasing carbohydrate consumption (P < .0001), and increasing unsaturated fat consumption (P = .002). CONCLUSIONS: The healthier trend of declining MetS severity in adolescents appeared to be due to favorable increases in HDL and decreases in fasting triglyceride measurements. These were in turn associated with favorable changes in dietary patterns among US adolescents. Future studies should investigate the causality of dietary differences on changes in MetS severity in adolescents.

Increases in Sex Hormones during Anti-Tumor Necrosis Factor α Therapy in Adolescents with Crohn's Disease.

OBJECTIVE: To evaluate children with Crohn's disease for inverse relationships between systemic inflammatory cytokines and sex hormone regulation in the context of anti-tumor necrosis factor α (TNF-α) therapy. STUDY DESIGN: An observational study design was used to assess sex hormone and gonadotropin levels at the time of initiation of anti-TNF-α therapy and 10 weeks and 12 months later in 72 adolescents (Tanner stage 2-5) with Crohn's disease. Mixed-model linear regression was used to evaluate relationships between hormone levels, systemic inflammation, and dual-energy x-ray absorptiometry whole-body fat mass Z scores over the study interval. RESULTS: Sex hormone Z scores increased significantly during the 10-week induction interval: testosterone Z scores in male patients increased from a median of -0.36 to 0.40 (P < .05) and estradiol Z scores in females increased from -0.35 to -0.02 (P < .01). In mixed model regression, the pediatric Crohn's disease activity index score, cytokine levels, and measures of inflammation were significantly and negatively associated with sex hormone Z scores and with luteinizing hormone and follicle-stimulating hormone levels, adjusted for sex and Tanner stage. Sex hormone and gonadotropin levels were not associated with body mass index or fat mass Z-scores. CONCLUSIONS: Crohn's disease is associated with delayed maturation, and initiation of anti-TNF-α therapy was associated with significant and rapid increases in sex hormone and gonadotropin levels, in association with improvements in disease activity and measures of inflammation. These data are consistent with preclinical studies of the effects of inflammation on sex hormone regulation.

Improvements in Bone Density and Structure during Anti-TNF-α Therapy in Pediatric Crohn's Disease.

CONTEXT: Pediatric Crohn's Disease (CD) is associated with deficits in trabecular bone mineral density (BMD) and cortical structure, potentially related to TNF-α effects to decrease bone formation and promote bone resorption. OBJECTIVE: This study aimed to examine changes in bone density and structure in children and adolescents with CD following initiation of anti-TNF-α therapy. DESIGN AND PARTICIPANTS: Participants (n = 74; age 5-21 years) with CD completed a 12-month prospective cohort study. MAIN OUTCOME MEASURES: Tibia peripheral quantitative computed tomography scans were obtained at initiation of anti-TNF-α therapy and 12 months later. Musculoskeletal outcomes were expressed as sex-and race-specific z scores relative to age, based on >650 reference participants. RESULTS: At baseline, CD participants had lower height, trabecular BMD, cortical area (due to smaller periosteal and larger endocortical circumferences), and muscle area z scores, compared with reference participants (all P < .01). Pediatric CD activity index decreased during the 10-week induction (P < .001), in association with subsequent gains in height, trabecular BMD, cortical area (due to recovery of endocortical bone), and muscle area z scores over 12 months (height P < .05; others P < .001). Bone-specific alkaline phosphatase levels, a biomarker of bone formation, increased a median of 75% (P < .001) during induction with associated 12-month improvements in trabecular BMD and cortical area z scores (both P < .001). Younger age was associated with greater increases in trabecular BMD z scores (P < .001) and greater linear growth with greater recovery of cortical area (P < .001). CONCLUSIONS: Anti-TNF-α therapy was associated with improvements in trabecular BMD and cortical structure. Improvements were greater in younger and growing participants, suggesting a window of opportunity for treatment of bone deficits.

Changes in vitamin D-related mineral metabolism after induction with anti-tumor necrosis factor-α therapy in Crohn's disease.

CONTEXT: Preclinical studies suggest that TNF-α suppresses PTH synthesis, inhibits renal 1α-hydroxylase activity, and impairs fibroblast growth factor 23 (FGF23) degradation. The impact of inflammation on vitamin D and mineral metabolism has not been well-characterized in Crohn's disease (CD). OBJECTIVE: The objective of the study was to assess short-term changes in vitamin D-related mineral metabolism in CD after anti-TNF-α induction therapy. DESIGN/PARTICIPANTS: Eighty-seven CD participants, aged 5-39 years, were assessed at the initiation of anti-TNF-α therapy and 10 weeks later. OUTCOMES: Indices of clinical disease activity and serum concentrations of vitamin D metabolites, vitamin D-binding protein (DBP), calcium, PTH, FGF23, IL-6, and TNF-α were measured at each visit. A multivariable generalized estimating equation (GEE) regression analysis was used to examine the correlates of PTH and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations at each visit. RESULTS: After anti-TNF-α therapy, cytokines and inflammatory markers [IL-6, TNF-α, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)] concentrations decreased (all P < .0001), and PTH and 1,25(OH)2D concentrations increased (median 21 vs 30 pg/mL, P < .0001, and median 41.7 vs 48.1 pg/mL, P = .014, respectively). Levels of 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D, DBP, and FGF23 did not change. In GEE analyses, higher IL-6, TNF-α, ESR, and CRP were associated with lower PTH concentrations (all P < .001), adjusted for corrected calcium and 25(OH)D levels. Higher PTH was associated with higher 1,25(OH)2D concentrations (P < .001) at each visit, independent of 25(OH)D concentrations. Higher levels of all inflammatory markers were associated with lower 1,25(OH)2D concentrations (all P < .05). However, when PTH was added to these models, the inflammatory markers (with the exception of CRP) were no longer significantly associated with 1,25(OH)2D. CONCLUSIONS: Greater inflammation was associated with lower PTH and 1,25(OH)2D concentrations. After anti-TNF-α induction, PTH and 1,25(OH)2D concentrations increased without concomitant changes in 25(OH)D and FGF23, consistent with effects of inflammation on PTH and thereby renal conversion of 25(OH)D to 1,25(OH)2D.

The use of ghrelin and ghrelin receptor agonists as a treatment for animal models of disease: efficacy and mechanism.

Ghrelin is a stomach-derived hormone that acts at the ghrelin receptor (formerly called the Growth Hormone Secretagogue (GHS)-1a receptor) in multiple tissues throughout the body, exhibiting pleotropic effects potentially beneficial as a treatment in human disease states. Given its properties including increasing appetite, decreasing systemic inflammation, decreasing vascular resistance, increasing cardiac output, and increasing growth hormone and IGF-1 levels, ghrelin has been tested as a treatment in animal models of multiple disease states that produce the deficits in these processes. Thus, the efficacy of ghrelin has been testing in diseases involving anorexia, negative energy balance, cardiovascular compromise, systemic inflammation and gastroparesis. These diseases include cancer cachexia, chronic heart failure, chronic renal failure, chemotherapy, arthritis, gastroparesis and inflammatory bowel disease. Across this wide variety of diseases treatment with ghrelin and ghrelin agonists have produced benefits, though given ghrelin's widespread effects, the exact mechanisms behind ghrelin's action in these settings is frequently difficult to determine. Further investigation using animal models may help to determine mechanisms that are most operative in these disease states and narrow treatment parameters helpful for human application.

Changes in inflammation and QoL after a single dose of infliximab during ongoing IBD treatment.

BACKGROUND AND OBJECTIVES: Infliximab is used increasingly as maintenance therapy for inflammatory bowel disease (IBD); however, the effects of a single maintenance dose of infliximab are unclear with respect to the quality of life and hormones related to growth and puberty. The aim of the present study was to determine the time course of inflammatory, hormonal, and quality-of-life changes following a single dose of infliximab in the context of ongoing therapy, as related to presence of IBD symptoms at time of administration. METHODS: Children and adolescents with IBD receiving ongoing therapy with infliximab for clinical indications were recruited. The Pediatric Crohn's Disease Activity Index was determined at baseline and laboratory measures of high-sensitivity C-reactive protein (hsCRP) and hormones of growth and puberty were determined on days 0, 2, and 14. IBD-related quality of life (IMPACT III questionnaire) was tested on days 0 and 14. Subjects who had symptoms of IBD were compared with asymptomatic subjects. RESULTS: Subjects overall and in the symptomatic group exhibited improved hsCRP by day 2 following treatment. Symptomatic subjects had higher Pediatric Crohn's Disease Activity Index scores and lower quality-of-life scores than asymptomatic subjects on day 0, whereas at day 14 there were no significant differences in quality-of-life scores between the 2 groups. CONCLUSIONS: Even in the context of ongoing treatment, a single dose of infliximab results in decreased hsCRP, an improvement that is particularly noted among subjects who are symptomatic at the time of treatment. Although randomized trials are needed, these observational data may assist clinicians, patients, and families regarding expectations about timing and extent of these changes following a single treatment dose.

Low sensitivity for the metabolic syndrome to detect uric acid elevations in females and non-Hispanic-black male adolescents: an analysis of NHANES 1999-2006.

BACKGROUND: Uric acid is tightly linked to the metabolic syndrome (MetS) and among adults higher uric acid levels are associated with future risk for diabetes, cardiovascular disease, hypertension and renal disease. OBJECTIVE: Evaluate the sensitivity of MetS to identify adolescents with elevated uric acid levels on a race/ethnicity and gender-specific basis. METHODS: We evaluated 3296 male and female adolescents 12-19 y participating in the National Health and Nutrition Evaluation Survey 1999-06, comprised of 67.6% non-Hispanic whites, 15.1% non-Hispanic blacks, and 17.3% Hispanics. We used a definition of MetS modified for use in adolescents and evaluated the sensitivity of a diagnosis of MetS to identify individuals with uric acid elevations (approximately the 95th percentile of uric acid by gender among normal-weight adolescents). RESULTS: When used as a screening test to identify individuals with uric acid elevations MetS performed more poorly among females (18.0%) than among males (37.0%) (p<0.001). Among males, MetS exhibited a lower sensitivity among non-Hispanic blacks (17.8%) compared to Hispanics (45.9%) (p<0.01) and non-Hispanic whites (37.4%) (p<0.05). There were no race/ethnicity differences in detecting elevated uric acid levels among females (non-Hispanic-white 15.5%, non-Hispanic-black 19.4%, Hispanic 26.5%, p>0.05). CONCLUSION: Current criteria to diagnose MetS exhibit racial/ethnic and gender differences in the ability to identify adolescents with elevated uric acid levels, performing poorly among non-Hispanic-black males and among females. Given emerging data regarding the ability of uric acid elevations for predicting future disease, these data may have implications regarding the use of MetS as a marker of risk among all gender and racial/ethnic groups.

Increased systemic inflammation overnight correlates with insulin resistance among children evaluated for obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) in children is associated with obesity, insulin resistance, and elevated baseline inflammation as measured by high-sensitivity C-reactive protein (hsCRP). Our goal was to evaluate whether inflammation increases overnight among children suspected of having OSA and to determine whether worsened inflammation is associated with the degree of OSA severity, obesity, and/or insulin resistance. METHODS: Twenty-three children with clinical suspicion of OSA underwent a sleep study. Levels of hsCRP were tested the evening before and morning after the sleep study. Fasting insulin and glucose levels were measured from which the homeostasis model of insulin resistance (HOMA-IR) was calculated. Linear correlations were performed to evaluate relationships between hsCRP levels at baseline and change overnight (ΔhsCRP) vs. HOMA-IR, body mass index (BMI) z-score, and sleep study parameters related to O(2) saturation and the apnea-hypopnea index (AHI). RESULTS: Among children with OSA and the entire cohort, hsCRP values were correlated with HOMA-IR and BMI z-scores. HOMA-IR but not BMI z-score correlated with ΔhsCRP overnight in the entire cohort. Sleep study parameters, including AHI mean O(2) saturation overnight, REM O(2) nadir, and non-REM O(2) nadir were not correlated with hsCRP or ΔhsCRP overnight. CONCLUSION: Among children being evaluated for OSA, degree of insulin resistance may be an important determinant of increased systemic inflammation overnight. Sleep study markers did not correlate with ΔhsCRP, leaving uncertain the role of OSA in increasing inflammation overnight. Further studies are needed to explore these associations and their potential mechanisms.