Dataset Information

Indirect Effects of Body Mass Index Growth on Glucose Dysregulation via Inflammation: Causal Moderated Mediation Analysis.

ABSTRACT:

Objective

No existing studies have examined the mediating role of chronic inflammation between obesity and dysregulated glucose homeostasis in adolescent samples. This study evaluated whether C-reactive protein (CRP), an inflammation biomarker, mediated the effects of growth (annual increase) in body mass index (BMI) on glycated hemoglobin (HbA1c).

Methods

BMI and biomarker data were used from wave I to wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health study; 4,545 adolescents; mean age = 14.9 years; 55.7% female) with valid CRP data. A causal moderated mediation analysis evaluated the direct and indirect effects of BMI slope on HbA1c via CRP across gender, with demographic and clinical characteristics as model covariates.

Results

The participants displayed a linear BMI growth of 0.53-0.58 kg/m2/year throughout adolescence, with substantial interindividual variation. The BMI slope showed positive direct and indirect effects on HbA1c via CRP across gender, and there was a significant exposure-mediator interaction effect. A standardized increase in the BMI slope raised the probability of an abnormal HbA1c value by 6.0-8.5% in participants with various profiles. The total natural indirect effect accounted for 13.3-15.9% of the total effect in males and 21.2-22.7% in females.

Conclusions

The findings provide support for the inflammation mechanism in the effects of adiposity on glucose homeostasis. In adolescents, excess BMI growth was linked with a higher risk of glucose dysregulation either directly or indirectly via chronic inflammation.

SUBMITTER: Fong TCT

PROVIDER: S-EPMC6696889 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Indirect Effects of Body Mass Index Growth on Glucose Dysregulation via Inflammation: Causal Moderated Mediation Analysis.

Fong Ted Chun Tat TCT

Obesity facts 20190527 3

<h4>Objective</h4>No existing studies have examined the mediating role of chronic inflammation between obesity and dysregulated glucose homeostasis in adolescent samples. This study evaluated whether C-reactive protein (CRP), an inflammation biomarker, mediated the effects of growth (annual increase) in body mass index (BMI) on glycated hemoglobin (HbA1c).<h4>Methods</h4>BMI and biomarker data were used from wave I to wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add ...[more]

PMID: 31132775

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Project description:BackgroundEmerging evidence suggests the potential mediating role of microbiome in health disparities. However, no analytic framework can be directly used to analyze microbiome as a mediator between health disparity and clinical outcome, due to the non-manipulable nature of the exposure and the unique structure of microbiome data, including high dimensionality, sparsity, and compositionality.MethodsConsidering the modifiable and quantitative features of the microbiome, we propose a microbial causal mediation model framework, SparseMCMM_HD, to uncover the mediating role of microbiome in health disparities, by depicting a plausible path from a non-manipulable exposure (e.g., ethnicity or region) to the outcome through the microbiome. The proposed SparseMCMM_HD rigorously defines and quantifies the manipulable disparity measure that would be eliminated by equalizing microbiome profiles between comparison and reference groups and innovatively and successfully extends the existing microbial mediation methods, which are originally proposed under potential outcome or counterfactual outcome study design, to address health disparities.ResultsThrough three body mass index (BMI) studies selected from the curatedMetagenomicData 3.4.2 package and the American gut project: China vs. USA, China vs. UK, and Asian or Pacific Islander (API) vs. Caucasian, we exhibit the utility of the proposed SparseMCMM_HD framework for investigating the microbiome's contributions in health disparities. Specifically, BMI exhibits disparities and microbial community diversities are significantly distinctive between reference and comparison groups in all three applications. By employing SparseMCMM_HD, we illustrate that microbiome plays a crucial role in explaining the disparities in BMI between ethnicities or regions. 20.63%, 33.09%, and 25.71% of the overall disparity in BMI in China-USA, China-UK, and API-Caucasian comparisons, respectively, would be eliminated if the between-group microbiome profiles were equalized; and 15, 18, and 16 species are identified to play the mediating role respectively.ConclusionsThe proposed SparseMCMM_HD is an effective and validated tool to elucidate the mediating role of microbiome in health disparity. Three BMI applications shed light on the utility of microbiome in reducing BMI disparity by manipulating microbial profiles. Video Abstract.

Dataset Information

Indirect Effects of Body Mass Index Growth on Glucose Dysregulation via Inflammation: Causal Moderated Mediation Analysis.

Objective

Methods

Results

Conclusions

Publications

Indirect Effects of Body Mass Index Growth on Glucose Dysregulation via Inflammation: Causal Moderated Mediation Analysis.

Similar Datasets

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