Obesity and overweight as CAE comorbidities and differential drug response modifiers

Childhood Absence Epilepsy Study Group

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)1613-1621
Number of pages9
JournalNeurology
Volume86
Issue number17
DOIs
StatePublished - Apr 26 2016

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Absence Epilepsy
Comorbidity
Obesity
Body Mass Index
Nutrition Surveys
Pharmaceutical Preparations
Energy Intake
Pharmacokinetics
Logistic Models
Carbohydrates
Ethosuximide
Valproic Acid
Demography
Weights and Measures
Population

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Obesity and overweight as CAE comorbidities and differential drug response modifiers. / Childhood Absence Epilepsy Study Group.

In: Neurology, Vol. 86, No. 17, 26.04.2016, p. 1613-1621.

Research output: Contribution to journalArticle

Childhood Absence Epilepsy Study Group. / Obesity and overweight as CAE comorbidities and differential drug response modifiers. In: Neurology. 2016 ; Vol. 86, No. 17. pp. 1613-1621.
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abstract = "Objective: 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. Methods: 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. Results: 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. Conclusions: 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.",
author = "{Childhood Absence Epilepsy Study Group} and Ravindra Arya and Gillespie, {Catherine W.} and Avital Cnaan and Mahima Devarajan and Peggy Clark and Shlomo Shinnar and Vinks, {Alexander A.} and Kana Mizuno and Glauser, {Tracy A.}",
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T1 - Obesity and overweight as CAE comorbidities and differential drug response modifiers

AU - Childhood Absence Epilepsy Study Group

AU - Arya, Ravindra

AU - Gillespie, Catherine W.

AU - Cnaan, Avital

AU - Devarajan, Mahima

AU - Clark, Peggy

AU - Shinnar, Shlomo

AU - Vinks, Alexander A.

AU - Mizuno, Kana

AU - Glauser, Tracy A.

PY - 2016/4/26

Y1 - 2016/4/26

N2 - Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

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