Endotoxemia, vitamin D and premature biological ageing in Arab adults with different metabolic states

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There are limited studies on the association of endotoxin, a potent mediator of gut-derived inflammation
and telomere length (TL). We investigated (1) the influence of adiposity on endotoxin and TL amongst
Saudi adults according to type 2 diabetes mellitus (T2DM) status and (2) the influence vitamin D may
have on TL attrition. Anthropometric data and fasting blood samples were taken from 775 Saudi adults
visiting different primary care centers in Riyadh [387 T2DM and 388 non-T2DM]. TL, derived from
peripheral blood mononuclear cells, was analyzed by Quantitative real-time polymerase chain reaction
and circulating endotoxin levels by Limulus Amebocyte Lysate assay. Subjects were stratified based on
obesity and T2DM status. A significant lower TL was observed in the non-obese T2DM group as compared
with their non-obese, non-T2DM counterparts (p = 0.002). Significant inverse associations between TL,
endotoxin and endotoxin activity were observed in the cohort with obesity. Regression analysis showed
that endotoxin was a significant predictor for TL in all subjects and even after stratification according to
subgroups; with variances perceived in circulating TL stronger among non-T2DM obese (10%; p = 0.003)
than non-T2DM non-obese (12%; p = 0.007). Also, in the non-T2DM group, TL and HDL-cholesterol predicted
29% of the variances perceived in 25(OH)D (p < 0.001). Taken together these findings show that
circulating endotoxin and 25(OH)D are associated with premature biological ageing influenced by adiposity
and metabolic state; suggesting future intervention studies to manipulate gut microbiome and
or vitamin D levels may offer ways to mitigate premature TL attrition.