Pediatric Obesity and Cardiometabolic Risk Linked to Serum Endotoxin Biomarkers

Serum endotoxin biomarkers were found to be associated with the development of childhood-onset cardiometabolic conditions and obesity. These findings, from a prospective study, were published in the Journal of Clinical Endocrinology & Metabolism.

Data for this study were sourced from the Exploring Perinatal Outcomes among CHildren (EPOCH) cohort. Children (N=395) who were born to a mother covered by the Kaiser Permanente of Colorado (KPCO) Health plan between 1995 and 2002 were included in the study. Participants were evaluated at a median of 10 and 16 years of age for cardiometabolic health and body composition, and serum samples were assessed for endotoxin and cardiometabolic biomarkers.

At baseline, the mean age of the cohort was 10.5±1.5 years, body mass index (BMI) z-score was 0.23±1.21, total cholesterol level was 222.3±102.1 mg/dL, fasting glucose was 82.3±14.4 mg/dL, and systolic blood pressure was 102.8±9.8 mm Hg.

Among the 3 endotoxin biomarkers evaluated — lipopolysaccharide, lipopolysaccharide binding protein, and endogenous endotoxin-core antibodies (EndoCab IgG) — maternal prepregnancy weight was found to be associated with both lipopolysaccharide (P =.002) and EndoCab IgG (P =.02), gestational diabetes was associated with lipopolysaccharide (P =.03), maternal education was associated with lipopolysaccharide (P =.006), child’s gender was associated with EndoCab IgG (P =.0001), ethnicity was associated with lipopolysaccharide (P =.008), child baseline weight status was associated with both lipopolysaccharide (P =.01) and lipopolysaccharide binding protein (P =.04), and child baseline pubertal status was associated with lipopolysaccharide (P =.007).

Stratified by gender, boys (n=199) were observed to have 70 correlations and girls (n=194) were observed to have 84 correlations among endotoxin biomarkers, adiposity, and metabolic biomarkers at baseline. In general, the correlations were stronger among girls. The strongest positive and negative correlations among boys and girls were between insulin level and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR; both ρ, 0.98) and LPS and high-density lipoprotein cholesterol level (boys: ρ, -0.24; girls: ρ, -0.29), respectively.

After correcting for age, gender, race, and maternal education, lipopolysaccharide and lipopolysaccharide binding protein predicted increased adiposity at follow-up, and lipopolysaccharide predicted increased cardiometabolic risk at follow-up.

In the fully adjusted models, lipopolysaccharide was found to be predictive of increases in skinfold sum (β, 5.32; 95% CI, 0.77-9.86; P =.0221), triglycerides (β, 0.15; 95% CI, 0.08-0.22; P <.0001), total cholesterol level (β, 0.22; 95% CI, 0.08-0.37; P =.0024), and low-density lipoprotein level (β, 0.18; 95% CI, 0.06-0.31; P =.0040).

In sensitivity analyses, some of the associations were attenuated by adjusting for total energy intake.

This study may have included reverse causation, as both lipopolysaccharide and lipopolysaccharide binding protein were associated with weight status at baseline.

This study found that serum endotoxin biomarkers may be a sign of the pathophysiologic process underling obesity and cardiometabolic outcomes among children.

Reference

Perng W, Friedman JE, Janssen RC, Glueck DH, Dabelea D. Endotoxin biomarkers are associated with adiposity and cardiometabolic risk across 6 years of follow-up in youth. J Clin Endocrinol Metab. Published March 11, 2022. doi:10.1210/clinem/dgac149