Mark D. DeBoer

Sugar-Sweetened Beverages and Weight Gain in 2- to 5-Year-Old Children

BACKGROUND AND OBJECTIVE: Although sugar-sweetened beverage (SSB) consumption has been tightly linked to weight status among older children, the data regarding these relationships in children aged 2 to 5 years have been mixed. Our objective was to evaluate longitudinal and cross-sectional relationships between SSB consumption and weight status among children aged 2 to 5 years. METHODS: We assessed SSB consumption and BMI z scores among 9600 children followed in the Early Childhood Longitudinal Survey—Birth Cohort, using linear and logistic regression and adjusting for race/ethnicity, socioeconomic status, mother’s BMI, and television viewing. RESULTS: Higher rates of SSB consumption were associated with higher BMI z scores among children age 4 (P < .05) and 5 (P < .001) but not yet at 2 years. Children aged 5 years who drank SSB regularly (compared with infrequent/nondrinkers) had a higher odds ratio for being obese (1.43, confidence interval 1.10–1.85, P < .01). In prospective analysis, children drinking SSB at 2 years (compared with infrequent/nondrinkers) had a greater subsequent increase in BMI z score over the ensuing 2 years (P < .05). CONCLUSIONS: Similar to what is seen among older children, children aged 2 to 5 years drinking SSB demonstrate both prospective and cross-sectional correlations with higher BMI z score. Pediatricians and parents should discourage SSB consumption to help avoid potential unhealthy weight gain in young children. From a public health standpoint, strong consideration should be made toward policy changes leading to decreases in SSB consumption among children.

Racial/ethnic discrepancies in the metabolic syndrome begin in childhood and persist after adjustment for environmental factors

BACKGROUND AND AIMS Evaluation of metabolic syndrome (MetS) characteristics across an age spectrum from childhood to adulthood has been limited by a lack of consistent MetS criteria for children and adults and by a lack of adjustment for environmental factors. We used the pediatric and adult International Diabetes Federation (IDF) criteria to determine whether gender-specific and race-specific differences in MetS and its components are present in adolescents as in adults after adjustment for socio-economic status (SES) and lifestyle factors. METHODS AND RESULTS Waist circumference, blood pressure, triglycerides, HDL cholesterol, and fasting glucose measures were obtained from 3100 adolescent (12-19 years) and 3419 adult (20-69 years) non-Hispanic white, non-Hispanic black, and Mexican-American participants of the 1999-2006 National Health and Nutrition Examination Surveys. We compared odds of having MetS and its components across racial/ethnic groups by age group, while adjusting for income, education, physical activity and diet quality. After adjusting for possible confounding influences of SES and lifestyle, non-Hispanic-black adolescent males exhibited a lower odds of MetS and multiple components (abdominal obesity, hypertriglyceridemia, low HDL, hyperglycemia) compared to non-Hispanic-white and Mexican-American adolescents. Compared to non-Hispanic-white adolescent males, Mexican-American adolescent males had less hypertension. There were no differences in MetS prevalence among adolescent females, though non-Hispanic-black girls exhibited less hypertriglyceridemia. CONCLUSION Racial/ethnicity-specific differences in MetS and its components are present in both adolescence and adulthood, even after adjusting for environmental factors. These data help strengthen arguments for developing racial/ethnic-specific MetS criteria to better identify individuals at risk for future cardiovascular disease.

Vitamin D Supplementation and Risk of Toxicity in Pediatrics: A Review of Current Literature

CONTEXT Although vitamin D toxicity is rare in children, increased use of vitamin D formulations, re-examination of optimal vitamin D levels, and use of higher doses lend potential for an increased incidence of vitamin D toxicity. EVIDENCE ACQUISITION A PubMed search was conducted through May 2013 for cases of vitamin D intoxication and vitamin D trials in pediatrics. Safety data were collected and reviewed. EVIDENCE SYNTHESIS A small number of pediatric studies tested vitamin D doses at or above the currently recommended upper tolerable intake. In children and adolescents, vitamin D excess was rare and usually asymptomatic. Recent cases of intoxication relate to errors in manufacturing, formulation, or prescription; involve high total intake in the range of 240,000 to 4,500,000 IU; and present with severe hypercalcemia, hypercalciuria, or nephrocalcinosis. However, mild hypercalcemia and hypervitaminosis using currently recommended doses have been reported in infants with rickets. CONCLUSIONS Although rare, cases of vitamin D intoxication that present with dramatic life-threatening symptoms still occur in children. Moreover, recent studies in infants raise a potential need for monitoring vitamin D levels when doses at or above the currently recommended upper range are used. Further studies are needed to clarify these findings. The Drugs and Therapeutics Committee of the Pediatric Endocrine Society suggests obtaining serum 25-hydroxyvitamin D levels in infants and children who receive long-term vitamin D supplementation at or above the upper level intake that is currently recommended.

A confirmatory factor analysis of the metabolic syndrome in adolescents: an examination of sex and racial/ethnic differences

ObjectiveThe metabolic syndrome (MetS) is a cluster of clinical indices that signals increased risk for cardiovascular disease and Type 2 diabetes. The diagnosis of MetS is typically based on cut-off points for various components, e.g. waist circumference and blood pressure. Because current MetS criteria result in racial/ethnic discrepancies, our goal was to use confirmatory factor analysis to delineate differential contributions to MetS by sub-group.Research Design and MethodsUsing 1999–2010 data from the National Health and Nutrition Examination Survey (NHANES), we performed a confirmatory factor analysis of a single MetS factor that allowed differential loadings across sex and race/ethnicity, resulting in a continuous MetS risk score that is sex and race/ethnicity-specific.ResultsLoadings to the MetS score differed by racial/ethnic and gender subgroup with respect to triglycerides and HDL-cholesterol. ROC-curve analysis revealed high area-under-the-curve concordance with MetS by traditional criteria (0.96), and with elevations in MetS-associated risk markers, including high-sensitivity C-reactive protein (0.71), uric acid (0.75) and fasting insulin (0.82). Using a cut off for this score derived from ROC-curve analysis, the MetS risk score exhibited increased sensitivity for predicting elevations in ≥2 of these risk markers as compared with traditional pediatric MetS criteria.ConclusionsThe equations from this sex- and race/ethnicity-specific analysis provide a clinically-accessible and interpretable continuous measure of MetS that can be used to identify children at higher risk for developing adult diseases related to MetS, who could then be targeted for intervention. These equations also provide a powerful new outcome for use in childhood obesity and MetS research.

Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations

Rationale: Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation‐prone asthma (EPA) remain incompletely defined. Objectives: To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA. Methods: Baseline data from the NHLBI Severe Asthma Research Program (SARP)‐3 were analyzed. An exacerbation was defined as a burst of systemic corticosteroids lasting 3 days or more. Patients were classified by their number of exacerbations in the past year: none, few (one to two), or exacerbation prone (≥3). Replication of a multivariable model was performed with data from the SARP‐1 + 2 cohort. Measurements and Main Results: Of 709 subjects in the SARP‐3 cohort, 294 (41%) had no exacerbations and 173 (24%) were exacerbation prone in the prior year. Several factors normally associated with severity (asthma duration, age, sex, race, and socioeconomic status) did not associate with exacerbation frequency in SARP‐3; bronchodilator responsiveness also discriminated exacerbation proneness from asthma severity. In the SARP‐3 multivariable model, blood eosinophils, body mass index, and bronchodilator responsiveness were positively associated with exacerbation frequency (rate ratios [95% confidence interval], 1.6 [1.2‐2.1] for every log unit of eosinophils, 1.3 [1.1‐1.4] for every 10 body mass index units, and 1.2 [1.1‐1.4] for every 10% increase in bronchodilatory responsiveness). Chronic sinusitis and gastroesophageal reflux were also associated with exacerbation frequency (1.7 [1.4‐2.1] and 1.6 [1.3‐2.0]), even after adjustment for multiple factors. These effects were replicated in the SARP‐1 + 2 multivariable model. Conclusions: EPA may be a distinct susceptibility phenotype with implications for the targeting of exacerbation prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 01760915).

An examination of sex and racial/ethnic differences in the metabolic syndrome among adults: A confirmatory factor analysis and a resulting continuous severity score

OBJECTIVE The metabolic syndrome (MetS) is typically diagnosed based on abnormalities in specific clustered clinical measures that are associated with increased risk for coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM). However, current MetS criteria result in racial/ethnic discrepancies. Our goals were to use confirmatory factor analysis (CFA) to delineate differential contributions to MetS by sub-group, and if contributions were discovered, develop sex and racial/ethnic-specific equations to calculate MetS severity. RESEARCH DESIGN AND METHODS Using data on adults from the National Health and Nutrition Examination Survey 1999-2010, we performed a CFA of a single MetS factor that allowed differential loadings across groups, resulting in a sex and race/ethnicity-specific continuous MetS severity score. RESULTS Loadings to the single MetS factor differed by sub-group for each MetS component (p<0.001), with lower factor loadings among non-Hispanic-blacks for triglycerides and among Hispanics for waist circumference. Systolic blood pressure exhibited low factor loadings among all groups. MetS severity scores were correlated with biomarkers of future disease (high-sensitivity C-reactive-protein, uric acid, insulin resistance). Non-Hispanic-black-males with diabetics had a low prevalence of MetS but high MetS severity scores that were not significantly different from other racial/ethnic groups. CONCLUSIONS This analysis among adults uniquely demonstrated differences between sexes and racial/ethnic groups regarding contributions of traditional MetS components to an assumed single factor. The resulting equations provide a clinically-accessible and interpretable continuous measure of MetS for potential use in identifying adults at higher risk for MetS-related diseases and following changes within individuals over time. These equations hold potential to be a powerful new outcome for use in MetS-focused research and interventions.

Emergence of ghrelin as a treatment for cachexia syndromes

Cachexia is a constellation of symptoms that amount to body wasting in the setting of a variety of chronic illnesses, including cancer, heart failure, chronic kidney disease, and acquired immunodeficiency syndrome. Cachexia is particularly worrisome clinically because it is associated with a worsened prognosis of the underlying disease. Despite a large amount of study in this area, no single agent has been shown to have consistent efficacy in human trials. One promising class in this setting is ghrelin receptor agonists. Ghrelin binds to the growth hormone secretagogue-1a receptor in appetite-regulating centers in the brain, increasing expression of neuropeptide Y and agouti-related peptide during short-term treatment. Ghrelin has also been shown to have anti-inflammatory properties, which is significant, given that cachexia is thought to be produced at least partly by inflammation induced by the underlying disease. Animal studies have demonstrated efficacy using growth hormone secretagogue receptor agonists to treat cachexia caused by cancer, chemotherapy, and chronic kidney disease. Limited human trials using ghrelin or ghrelin receptor agonists in cancer and heart disease have shown improved appetite and body mass during treatment, although longer-term trials are needed to confirm sustained effects. Also uncertain--but an intriguing possibility--is whether the improved weight gain with ghrelin treatment might also lessen the severity of the underlying disease and improve outcomes.

Biomarkers of environmental enteropathy, inflammation, stunting, and impaired growth in children in Northeast Brazil

Critical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6–26 month-old children with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m. Biomarkers that correlated with stunting included plasma IgA anti-LPS and anti-FliC, zonulin (if >12m old), and intestinal FABP (I-FABP, suggesting prior barrier disruption); and with citrulline, tryptophan and with lower serum amyloid A (SAA) (suggesting impaired defenses). In contrast, subsequent growth was predicted in those with higher fecal MPO or A1AT and also by higher L/M, plasma LPS, I-FABP and SAA (showing intestinal barrier disruption and inflammation). Better growth was predicted in girls with higher plasma citrulline and in boys with higher plasma tryptophan. Interactions were also seen with fecal MPO and neopterin in predicting subsequent growth impairment. Biomarkers clustered into markers of 1) functional intestinal barrier disruption and translocation, 2) structural intestinal barrier disruption and inflammation and 3) systemic inflammation. Principle components pathway analyses also showed that L/M with %L, I-FABP and MPO associate with impaired growth, while also (like MPO) associating with a systemic inflammation cluster of kynurenine, LBP, sCD14, SAA and K/T. Systemic evidence of LPS translocation associated with stunting, while markers of barrier disruption or repair (A1AT and Reg1 with low zonulin) associated with fecal MPO and neopterin. We conclude that key noninvasive biomarkers of intestinal barrier disruption, LPS translocation and of intestinal and systemic inflammation can help elucidate how we recognize, understand, and assess effective interventions for enteropathy and its growth and developmental consequences in children in impoverished settings.

Diagnosis of the metabolic syndrome is associated with disproportionately high levels of high-sensitivity C-reactive protein in non-Hispanic black adolescents: an analysis of NHANES 1999-2008.

OBJECTIVE Whereas it is known that the metabolic syndrome (MetS) has a paradoxically lower prevalence in non–Hispanic black adolescents than in non–Hispanic whites or Hispanics, the relative severity of MetS by race/ethnicity is unknown. Inflammation, indicated by high-sensitivity C-reactive protein (hsCRP), is a key factor linking MetS to cardiovascular disease and type 2 diabetes. Our goal was to determine whether elevations of hsCRP vary by race/ethnicity among adolescents with MetS. RESEARCH DESIGN AND METHODS We used the National Health and Nutrition Examination Survey (1999–2008) and evaluated adolescents (age 12–19 years) using a pediatric/adolescent adaptation of the ATP III definition of MetS. We used linear regression to evaluate the interaction between MetS status and ethnicity with respect to hsCRP concentration. RESULTS For male and female adolescents, MetS was associated with elevated hsCRP levels compared with adolescents without MetS. However, the elevation in hsCRP between adolescents with and without MetS was greater in non–Hispanic blacks compared with that in non–Hispanic whites (P = 0.04) but not that in Hispanics (P = 0.18). hsCRP concentrations correlated with individual MetS components similarly among all ethnicities. In an evaluation of adolescents diagnosed with MetS, non–Hispanic blacks had higher BMI and more hypertension than other ethnicities but there were no other racial/ethnic differences in the features of MetS. CONCLUSIONS Non–Hispanic black adolescents have a greater differential in hsCRP between those with and those without MetS than the differential in non–Hispanic whites but not that in Hispanics. Therefore, even though MetS has a low prevalence in non–Hispanic blacks, MetS is a particularly good indicator of inflammation in non–Hispanic black adolescents.

Ethnicity, obesity and the metabolic syndrome: implications on assessing risk and targeting intervention

Pediatric obesity threatens the future health of a growing number of children worldwide. An added challenge in identifying the patients at greatest need for intervention due to their elevated risk for future disease is that pediatric obesity and the associated metabolic syndrome manifest differently among different ethnic groups. African–Americans and Hispanics are more likely to exhibit obesity and insulin resistance and are at a higher risk for developing Type 2 diabetes. Nevertheless, using current criteria, African–American adolescents are much less likely to be diagnosed with metabolic syndrome, largely owing to lower rates of dyslipidemia. Further development is needed in ethnicity-inclusive means of risk identification among adolescents to accurately target treatment toward children at highest risk for future disease and to motivate adolescent patients and their families towards lifestyle improvement. Effective targeting and intensive treatment efforts may help in avoiding future sequelae of obesity among all ethnicities.