Metabolomic Profiles of Sleep-Disordered Breathing are Associated with Hypertension and Diabetes Mellitus Development: the HCHS/SOL

Abstract

Sleep-disordered breathing (SDB) is a prevalent disorder characterized by recurrent episodic upper airway obstruction. In a dataset from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we applied principal component analysis (PCA) on seven measures characterizing SDB-associated respiratory events. We estimated the association of the top two SDB PCs with serum levels of 617 metabolites, in both single-metabolite analysis, and a joint, penalized regression analysis using the least absolute shrinkage and selection operator (LASSO). Discovery analysis included n = 3,299 HCHS/SOL individuals; associations were validated in a separate dataset of n = 1,522 HCHS/SOL individuals. Seven metabolite associations with SDB PCs were discovered and replicated. Metabolite risk scores (MRSs) developed based on LASSO association results and representing metabolite signatures associated with the two SDB PCs were associated with 6-year incident hypertension and incident diabetes. MRSs have the potential to serve as biomarkers for SDB, guiding risk stratification and treatment decisions.

Untargeted Metabolome Atlas for Sleep Phenotypes in the Hispanic Community Health Study/Study of Latinos

“…Both lipids and cofactors/vitamins had subpathways (e.g., ketone bodies, acyl glutamine, pantothenate and CoA metabolism, nicotinate and nicotinamide metabolism) that had high percentage of statistically significant associations with sleep timing phenotypes. SDB phenotypes had the highest percentage of statistically significant associations among lipids, especially progestin steroids, phosphatidylethanolamine, diacylglycerols, pregnenolone steroids and sphingomyelins, which is consistent with our previous research findings (43). As for the sleep duration domain, the top subpathways with the highest percentage of significant associations were bacterial/fungal, amino sugar metabolism, nicotinate and nicotinamide metabolism, primary bile acid metabolism, corticosteroids, and polyamine metabolism.…”

“…In a recent study, glycine was found to be depleted in blood among Hispanic/Latino individuals with severe SDB, likely due to microbiome changes in an oxygen-poor environment (46). Four other metabolites – 1-oleoyl-GPE (18:1), 1-(1-enyl-palmitoyl)-GPC (P-16:0)*, pregnenolone sulfate, 5alpha-pregnan-3beta,20alpha-diol monosulfate (2), previously reported to be associated with novel SDB phenotype metrics after dimension reduction in our prior work in HCHS/SOL (43), were here also associated with several SDB phenotypes as well as with phenotypes from domains including insomnia, sleep timing, and heart rate during sleep.…”