Endothelial function typically exhibits a hormetic response to exercise. It is unknown whether endothelial damage occurs in response to acute exercise and could be a contributing mechanism. We sought to determine the effects of acute exercise on endothelial-derived circulating factors proposed to reflect endothelial integrity and activation. Young, healthy men ( n = 10) underwent 30-min moderate continuous (MOD) and high-intensity interval (HII) cycling exercise bouts. Venous blood samples were taken immediately before and after exercise for quantification of circulating endothelial cells (CECs), circulating angiogenic cells (CACs), apoptotic and activated endothelial microvesicles (EMVs), thrombomodulin (TM), von Willebrand factor (vWF), syndecan-1, and circulating microRNAs (ci-miRs) 126–3p and 126–5p. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery before, 10 min after, and 60 min after exercise. Numbers of CECs and EMVs were unchanged by either exercise bout ( P > 0.05). Numbers of all measured CAC subtypes decreased in response to MOD (21%–34%, P < 0.05), whereas only CD31+/34+/45dim/− CACs decreased following HII (21%, P < 0.05). TM and syndecan-1 increased with both exercise intensities (both ~20%, P < 0.05). HII, but not MOD, increased vWF (88%, P < 0.001), ci-miR-126–3p (92%, P = 0.009) and ci-miR-126–5p (110%, P = 0.01). The changes in several circulating factors correlated with changes in FMD following either one or both intensities. Changes in circulating factors do not support the concept of exercise-induced endothelial cell denudation, apoptosis, or activation, though slight disruption of endothelial glycocalyx and membrane integrity may occur. A related loss of mechanotransduction along with mechanisms underlying endothelial activation and ci-miR-126 secretion may relate to changes in endothelial function. NEW & NOTEWORTHY Using circulating endothelial-derived factors, we show that endothelial denudation, apoptosis, and activation do not appear to increase, whereas disrupted endothelial glycocalyx and membrane integrity may occur during both high-intensity interval and moderate intensity cycling. Increases in factors nonspecific to endothelial damage, including von Willebrand factor and microRNA-126, occurred only after high-intensity interval exercise. These results shed light on the hypothesis that disrupted endothelial integrity contributes to the endothelial function response to exercise.

OBJECTIVE The efficacy and safety of continuous glucose monitoring (CGM) in adjusting inpatient insulin therapy have not been evaluated. RESEARCH DESIGN AND METHODS This randomized trial included 185 general medicine and surgery patients with type 1 and type 2 diabetes treated with a basal-bolus insulin regimen. All subjects underwent point-of-care (POC) capillary glucose testing before meals and bedtime. Patients in the standard of care (POC group) wore a blinded Dexcom G6 CGM with insulin dose adjusted based on POC results, while in the CGM group, insulin adjustment was based on daily CGM profile. Primary end points were differences in time in range (TIR; 70–180 mg/dL) and hypoglycemia (&lt;70 mg/dL and &lt;54 mg/dL). RESULTS There were no significant differences in TIR (54.51 ± 27.72 vs. 48.64 ± 24.25%; P = 0.14), mean daily glucose (183.2 ± 40 vs. 186.8 ± 39 mg/dL; P = 0.36), or percent of patients with CGM values &lt;70 mg/dL (36 vs. 39%; P = 0.68) or &lt;54 mg/dL (14 vs. 24%; P = 0.12) between the CGM-guided and POC groups. Among patients with one or more hypoglycemic events, compared with POC, the CGM group experienced a significant reduction in hypoglycemia reoccurrence (1.80 ± 1.54 vs. 2.94 ± 2.76 events/patient; P = 0.03), lower percentage of time below range &lt;70 mg/dL (1.89 ± 3.27% vs. 5.47 ± 8.49%; P = 0.02), and lower incidence rate ratio &lt;70 mg/dL (0.53 [95% CI 0.31–0.92]) and &lt;54 mg/dL (0.37 [95% CI 0.17–0.83]). CONCLUSIONS The inpatient use of real-time Dexcom G6 CGM is safe and effective in guiding insulin therapy, resulting in a similar improvement in glycemic control and a significant reduction of recurrent hypoglycemic events compared with POC-guided insulin adjustment.

Endogenous sex hormone concentrations vary between healthy naturally menstruating (non-OCP) and oral contraceptive pill-using (OCP) women, as well as across cycles. The aim of this study was to investigate potential differences in concentrations of inflammatory cytokine, interleukin-6 (IL-6), vasoconstrictive substance, endothelin-1 (ET-1), and measures of vascular function among relatively lower and higher hormone phases of non-OCP and OCP. Concentrations of estrogen, progesterone, IL-6 and ET-1 and measures of vascular function were collected in 22 women (22±1 y, OCP: n=12) during the early follicular (EF, ≤5 days of menstruation onset) and early luteal (EL, 4±2 days post-ovulation) phases of non-OCP and were compared to the placebo pill (PP, ≤5 days of PP onset) and active pill (AP, ≤5 days of highest dose AP) phases of OCP. Vascular function was assessed via brachial artery flow-mediated dilation (%FMD). Concentrations of endogenous estrogen and progesterone were higher in the EL phase as compared to the EF phase of non-OCP (p=0.01) but were similar between phases of OCP (p>0.05). IL-6 was higher in non-OCP during the EF phase as compared to the EL phase as well as compared to OCP during the PP phase (p=0.002) but was similar between groups during the EL and AP phases, respectively (p>0.05). Concentrations of ET-1 and measures of %FMD were similar between groups and unaffected by phase (p>0.05). Thus, there exists variation in inflammation between young, healthy non-OCP and OCP during the lower hormone phase, despite similarities in vascular function and concentrations of ET-1 between groups and phases.

Both aberrant vascular reactivity to acute cardiovascular stress and epigenetic mechanisms such as microRNA (miR) may underlie the increased propensity for African Americans (AA) to develop cardiovascular disease. This study assessed racial differences in acute induced endothelial inflammation and related miRs. Cultured human umbilical vein endothelial cells (HUVECs) derived from AA and Caucasian Americans (CA) were exposed to the influenza vaccine to determine changes in inflammatory markers, endothelial nitric oxide synthase (eNOS), and miR expression/release. Endothelial function (flow-mediated dilation [FMD]), circulating IL-6, and circulating miR were also measured in young, healthy AA and CA individuals before and after receiving the influenza vaccine. There were no significant racial differences in any parameters at baseline. The vaccine induced increases in IL-6 release (24%, P=0.02) and ICAM-1 mRNA (40%, P=0.03), as well as reduced eNOS mRNA (24%, P=0.04) in AA HUVECs, but not in CA HUVECs (all P>0.05). Intracellular levels of anti-inflammatory miR-221-3p and miR-222-3p increased specifically in CA HUVECs (72% and 53%, p=0.04 and p=0.06), while others did not change in either race. HUVEC secretion of several miRs decreased in both races, while the release of anti-inflammatory miR-150-5p was decreased only by AA cells (-30%, P=0.03). In individuals of both races, circulating IL-6 increased ~two-fold 24 hours after vaccination (both P<0.01) and returned to baseline levels by 48 hours, while FMD remained unchanged. Although macrovascular function was unaffected by acute inflammation in AA and CA individuals, AA endothelial cells exhibited increased susceptibility to acute inflammation and unique changes in related miR.

High-intensity interval (HII) exercise elicits distinct vascular responses compared to a matched dose of moderate intensity continuous (MOD) exercise. However, the acute effects of HII compared to MOD exercise on arterial stiffness are incompletely understood. Circulating microRNAs (ci-miRs) may contribute to the vascular effects of exercise. We sought to determine exercise intensity-dependent changes in ci-miR potentially underlying changes in arterial stiffness. Ten young, healthy men underwent well-matched, 30-min HII and MOD exercise bouts. RT-qPCR was used to determine the levels of seven vascular-related ci-miRs in serum obtained immediately before and after exercise. Arterial stiffness measures including carotid to femoral pulse wave velocity (cf-PWV), carotid arterial compliance and β-stiffness, and augmentation index (AIx and AIx75) were taken before, 10min after and 60min after exercise. Ci-miR-21-5p, 126-3p, 126-5p, 150-5p, 155-5p, and 181b-5p increased after HII exercise (p < .05), while ci-miR-150-5p and 221-3p increased after MOD exercise (p = .03 and 0.056). One hour after HII exercise, cf-PWV trended toward being lower compared to baseline (p = .056) and was significantly lower compared to 60min after MOD exercise (p = .04). Carotid arterial compliance was increased 60min after HII exercise (p = .049) and was greater than 60min after MOD exercise (p = .02). AIx75 increased 10 min after both HII and MOD exercise (p < .05).There were significant correlations between some of the exercise-induced changes in individual ci-miRs and changes in cf-PWV and AIx/AIx75. These results support the hypotheses that arterial stiffness and ci-miRs are altered in an exercise intensitydependent manner, and ci-miRs may contribute to changes in arterial stiffness.