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Obesity and overweight as CAE comorbidities and differential drug response modifiers.

ABSTRACT: This study examined whether overweight and obesity are pretreatment comorbidities and predictors of short-term drug response in newly diagnosed untreated childhood absence epilepsy (CAE). We also examined whether dietary intake accounts for observed pretreatment body mass index (BMI) distribution.Pretreatment height and weight were available for 445 of 446 participants in the NIH-funded CAE comparative effectiveness trial (NCT00088452). Twenty-four-hour dietary recalls were collected. Calculated BMI and dietary intake were standardized for age, sex, and race/ethnicity and compared to age-matched US population from the National Health and Nutrition Examination Survey (NHANES). Logistic regression models tested BMI as a predictor of treatment response. Pharmacokinetic variables were explored as contributors to differential drug response.After standardizing for demographic differences, children with CAE were more likely to be overweight (19.3% vs 13.8%; p < 0.001) or obese (14.5% vs 11.5%; p < 0.001) than NHANES controls. The combined prevalence of overweight and obesity was 33.8% in the CAE cohort and 25.3% among controls (p < 0.001). Mean daily energy intake (difference -79.5 kcal/day, p = 0.04) and daily carbohydrate intake (difference -10.7 g/day, p = 0.04) were lower in the CAE group than in NHANES controls. With increasing baseline BMI z score, the efficacy and effectiveness of ethosuximide and valproic acid over lamotrigine became more pronounced, despite no significant differences in drug exposure and trough levels.Overweight and obesity are more prevalent in children with newly diagnosed CAE than in age-matched peers, despite lower caloric and carbohydrate intake. Baseline BMI may also predict differential drug response, which cannot be attributed to pharmacokinetic differences.

SUBMITTER: Arya R

PROVIDER: S-EPMC4844235 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Obesity and overweight as CAE comorbidities and differential drug response modifiers.

Arya Ravindra R Gillespie Catherine W CW Cnaan Avital A Devarajan Mahima M Clark Peggy P Shinnar Shlomo S Vinks Alexander A AA Mizuno Kana K Glauser Tracy A TA

Neurology 20160330 17

<h4>Objective</h4>This study examined whether overweight and obesity are pretreatment comorbidities and predictors of short-term drug response in newly diagnosed untreated childhood absence epilepsy (CAE). We also examined whether dietary intake accounts for observed pretreatment body mass index (BMI) distribution.<h4>Methods</h4>Pretreatment height and weight were available for 445 of 446 participants in the NIH-funded CAE comparative effectiveness trial (NCT00088452). Twenty-four-hour dietary ...[more]

PMID: 27029636

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Project description:Background and aims: Youth populations with overweight/obesity (OW/OB) exhibit heterogeneity in cardiometabolic health phenotypes (e.g. fasting glucose, serum triglycerides, etc.). The underling mechanisms for those differences are still unclear. This study aimed to analyze the whole blood transcriptome profile (RNA-seq) of children with metabolic healthy overweight/obesity (MHO) and metabolic unhealthy overweight/obesity (MUO) phenotypes. Methods: 27 children with OW/OB (10.14 ± 1.3 years, 59% boys) from the ActiveBrains project were included. MHO was defined as having none of the following criteria for metabolic syndrome: elevated fasting glucose, high serum triglycerides, low high-density lipoprotein cholesterol, and high systolic or diastolic blood pressure, while MUO was defined as presenting one or more of these criteria. Inflammatory markers interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), epidermal growth factor (EGF) and, vascular endothelial growth factor A (VEGF) were additionally determined. Total-blood RNA was analyzed by 5’-end RNA sequencing. Two different bioinformatics approaches were performed: 1) Differential gene expression analyses using Limma R/Bioconductor software package (analyses adjusted by sex and maturational status) and 2) weighted gene coexpression network analyses (WGCNA). Results: Children with MHO had lower values of pro-inflammatory cytokines TNF-α and IL-6 compared to MUO (p < 0.05). 40 genes were differentially expressed (FDR < 0.05) in children with MHO compared to MUO. WGCNA analysis identified 23 gene coexpression modules (i.e. clusters of genes) with low preservation (Zsummary < 2) in children with MHO compared to MUO. Differential and WGCNA gene expression patterns identified 32 genes linked to metabolism, mitochondrial and immune functions. Conclusions: Whole blood transcriptome analysis revealed a distinct pattern of gene expression in children with MHO compared to MUO children. The identified gene expression patterns related to metabolism, mitochondrial and immune functions can promote a better understanding of cardiovascular disease prognosis in individuals with MHO.

Project description:ObjectivesThe purpose of this study is to assess the prevalence of overweight/obesity, abdominal obesity and obesity-related risk factors in southern China.MethodsA cross-sectional survey of 15,364 participants aged 15 years and older was conducted from November 2013 to August 2014 in Jiangxi Province, China, using questionnaire forms and physical measurements. The physical measurements included body height, weight, waist circumference (WC), body fat percentage (BFP) and visceral adipose index (VAI). Multivariate logistic regression analysis was performed to evaluate the risk factors for overweight/obesity and abdominal obesity.ResultsThe prevalence of overweight was 25.8% (25.9% in males and 25.7% in females), while that of obesity was 7.9% (8.4% in males and 7.6% in females). The prevalence of abdominal obesity was 10.2% (8.6% in males and 11.3% in females). The prevalence of overweight/obesity was 37.1% in urban residents and 30.2% in rural residents, and this difference was significant (P < 0.001). Urban residents had a significantly higher prevalence of abdominal obesity than rural residents (11.6% vs 8.7%, P < 0.001). Among the participants with an underweight/normal body mass index (BMI), 1.3% still had abdominal obesity, 16.1% had a high BFP and 1.0% had a high VAI. Moreover, among obese participants, 9.7% had a low /normal WC, 0.8% had a normal BFP and 15.9% had a normal VAI. Meanwhile, the partial correlation analysis indicated that the correlation coefficients between VAI and BMI, VAI and WC, and BMI and WC were 0.700, 0.666, and 0.721, respectively. A multivariate logistic regression analysis indicated that being female and having a high BFP and a high VAI were significantly associated with an increased risk of overweight/obesity and abdominal obesity. In addition, living in an urban area and older age correlated with overweight/obesity.ConclusionThis study revealed that obesity and abdominal obesity, which differed by gender and age, are epidemic in southern China. Moreover, there was a very high, significant, positive correlation between WC, BMI and VAI. However, further studies are needed to explore which indicator of body fat could be used as the best marker to indirectly reflect cardiometabolic risk.

Dataset Information

Obesity and overweight as CAE comorbidities and differential drug response modifiers.

Publications

Obesity and overweight as CAE comorbidities and differential drug response modifiers.

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