Abstract
AimGut leakage has been shown to associate with low-grade inflammation and lower cardiorespiratory fitness in diabetic subjects. We aimed to investigate whether gut leakage markers related to cardiorespiratory fitness in patients with both coronary artery disease and type 2 diabetes, and whether these were affected by long-term exercise training.MethodsPatients with angiographically verified coronary artery disease and type 2 diabetes mellitus (n = 137) were randomized to either 12 months exercise intervention or conventional follow-up. A cardiopulmonary exercise test and fasting blood samples were obtained before and after intervention to assess VO2peak and the biomarkers soluble CD14, lipopolysaccharide-binding protein and intestinal fatty-acid binding protein as markers of gut leakage.Results114 patients completed the intervention satisfactory. VO2peak correlated inversely to sCD14 (r = − 0.248, p = 0.004) at baseline. Dividing sCD14 into quartiles (Q), VO2peak was significantly higher in Q1 vs. Q2–4 (p = 0.001), and patients in Q2-4 (sCD14 > 1300 ng/mL) had an OR of 2.9 (95% CI 1.2–7.0) of having VO2peak below median (< 23.8 ml/kg/min) at baseline. There were no statistically significant differences in changes in gut leakage markers between the two randomized groups (all p > 0.05) after 12 months.ConclusionsCardiorespiratory fitness related inversely to sCD14, suggesting physical capacity to be associated with gut leakage in patients with CAD and T2DM. Long-term exercise training did not affect circulating gut leakage markers in our population.Trial registration NCT01232608, Registered 02 November 2010—Retrospectively registered at https://clinicaltrials.gov/ct2/show/NCT01232608?term=NCT01232608&draw=2&rank=1
Highlights
Intestinal dysbiosis and gut leakage is hypothesized to contribute to the chronic low-grade inflammatory state associated with obesity, insulin resistance andAune et al Diabetol Metab Syndr (2021) 13:36 atherosclerotic cardiovascular disease (CVD) [1, 2]
LPS in the circulation interacts with LPS-binding protein (LBP), membrane bound or soluble CD14, activating the toll-like receptor 4 (TLR4) and initiating downstream inflammatory signaling [4]
intestinal fatty acid-binding protein (I-FABP) was determined in serum, measured by enzyme-linked immunosorbent assay (ELISA) (Hycult Biotech, Uden, the Netherlands). soluble CD14 (sCD14) and LBP were measured in EDTA plasma by ELISAs (R&D Systems Europe, Abingdon, Oxon, UK and Hycult Biotech, respectively)
Summary
Intestinal dysbiosis and gut leakage is hypothesized to contribute to the chronic low-grade inflammatory state associated with obesity, insulin resistance andAune et al Diabetol Metab Syndr (2021) 13:36 atherosclerotic cardiovascular disease (CVD) [1, 2]. Intestinal dysbiosis and gut leakage is hypothesized to contribute to the chronic low-grade inflammatory state associated with obesity, insulin resistance and. Gut leakage describes the translocation of bacterial wall products, mainly lipopolysaccharide (LPS), across the gut barrier by either para- or transcellular mechanisms, or by enterocyte damage with subsequent leakage of the intracellular intestinal fatty acid-binding protein (I-FABP) into the circulation [3]. LPS in the circulation interacts with LPS-binding protein (LBP), membrane bound or soluble CD14 (sCD14), activating the toll-like receptor 4 (TLR4) and initiating downstream inflammatory signaling [4]. Elevated levels of LBP and sCD14 have been associated with insulin resistance and obesity [5], and with coronary artery disease (CAD) and all-cause mortality [6, 7]. I-FABP is regarded as a marker of intestinal injury or ischemia [10]
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