Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes

Abstract

Premature aging, as denoted by a reduced telomere length (TL), has been observed in several chronic inflammatory diseases, such as obesity and type 2 diabetes mellitus (T2DM). However, no study to date has addressed the potential inflammatory influence of the gut-derived Gram-negative bacterial fragments lipopolysaccharide, also referred to as endotoxin, and its influence on TL in low-grade inflammatory states such as type 2 diabetes mellitus (T2DM). The current study therefore investigated the influence of endotoxin and inflammatory factors on telomere length (TL) in adults with (T2DM: n = 387) and without (non-diabetic (ND) controls: n = 417) obesity and T2DM. Anthropometric characteristics were taken, and fasted blood samples were used to measure biomarkers, TL, and endotoxin. The findings from this study highlighted across all participants that circulating endotoxin (r = −0.17, p = 0.01) was inversely associated with TL, noting that endotoxin and triglycerides predicted 18% of the variance perceived in TL (p < 0.001). Further stratification of the participants according to T2DM status and sex highlighted that endotoxin significantly predicted 19% of the variance denoted in TL among male T2DM participants (p = 0.007), where TL was notably influenced. The influence on TL was not observed to be impacted by anti-T2DM medications, statins, or anti-hypertensive therapies. Taken together, these results show that TL attrition was inversely associated with circulating endotoxin levels independent of the presence of T2DM and other cardiometabolic factors, suggesting that low-grade chronic inflammation may trigger premature biological aging. The findings further highlight the clinical relevance of mitigating the levels of circulating endotoxin (e.g., manipulation of gut microbiome) not only for the prevention of chronic diseases but also to promote healthy aging.

Association of bone mineralization markers with dietary nutrient intake in adolescents with and without biochemical osteomalacia

“…Excessive media use, which promotes sedentary lifestyle and negatively affects food choices is particularly common among Saudi adolescents (33), and aggravates this situation. Furthermore, the high consumption of phosphate-derivative foods such as processed foods and beverages confirm a previous survey among almost 11,000 Saudis especially in the young population (34). Interestingly, the low dietary Ca intake in Saudi adolescents extends to their adult counterparts already at risk of osteoporosis, with an average Ca intake of only 445 mg/day (RDI of 1,300 mg/day) (35).…”

“…Common factors for vitamin deficiency in SA include extreme heat during summer season, as well as cultural/religious factors such as the full covering of (mostly) women when going outdoors (8). In SA alone, vitamin D deficiency has been linked to a host of extra-skeletal disorders such as cardiovascular disease (9), type 2 diabetes mellitus (10), and premature biological ageing (11). Most of these studies however were conducted in adults, and available data on extra-skeletal effects of vitamin D deficiency in younger Arab populations are scarce.…”

Differences and Associations of NLRP3 Inflammasome Levels with Interleukins 1α, 1β, 33 and 37 in Adults with Prediabetes and Type 2 Diabetes Mellitus

“…In the Middle East, particularly in the Kingdom of Saudi Arabia (KSA), one out of every four adults has diabetes, mainly T2DM. By 2031, the incidence of T2DM in KSA is expected to double [2]. T2DM is a multi-factorial noncommunicable disorder that is notorious for causing insulin resistance and long-lasting sub-clinical inflammation with elevated systemic levels of adipokines, tumor necrosis factor (TNF) and interleukins (IL) [3].…”

“…Altered adipocytes secondary to obesity have been observed to overexpress hormones and inflammatory cytokines, causing obese individuals to be highly susceptible to long-term chronic inflammation [4]. Thus, increased adipocytes negatively amplify the inflammatory response, leading to insulin resistance and, ultimately, the development of T2DM [2]. Since obesity is correlated with the stimulation of the innate Biomedicines 2023, 11, 1315 2 of 12 immune system, the analysis of various inflammatory markers is highly significant in managing and treating T2DM [4].…”

Genetic Variants of HNF4A, WFS1, DUSP9, FTO, and ZFAND6 Genes Are Associated with Prediabetes Susceptibility and Inflammatory Markers in the Saudi Arabian Population

“…Type 2 diabetes mellitus (T2DM) is one of the most prevalent multifactorial chronic disorders, characterized by impaired glucose tolerance and insulin sensitivity, leading to hyperglycemia in both fasting and postprandial states [ 1 , 2 , 3 ]. It is a rising epidemic of the last century, globally affecting 536.6 million adults aged 20–79 and projected to escalate to 783.2 million by 2045 [ 4 ].…”