Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes.

BACKGROUND: Endogenous estrogen is cardio-protective in healthy premenopausal women. Despite this favorable action of estrogen, animal models depict a detrimental effect of estradiol on vascular function in the presence of diabetes. The present study sought to determine the role of endogenous estradiol on endothelial function in women with type 1 diabetes. METHOD: 32 women with type 1 diabetes (HbA1c = 8.6 ± 1.7%) and 25 apparently healthy women (HbA1c = 5.2 ± 0.3%) participated. Flow-mediated dilation (FMD), a bioassay of nitric-oxide bioavailability and endothelial function was performed during menses (M) and the late follicular (LF) phase of the menstrual cycle to represent low and high concentrations of estrogen, respectively. In addition, a venous blood sample was collected at each visit to determine circulating concentrations of estradiol, thiobarbituric acid reactive substances (TBARS), and nitrate/nitrite (NOx), biomarkers of oxidative stress and nitric oxide, respectively. Data were collected in (1) 9 additional women with type 1 diabetes using oral hormonal birth control (HBC) (HbA1c = 8.3 ± 2.1%) during the placebo pill week and second active pill week, and (2) a subgroup of 9 demographically matched women with type 1 diabetes not using HBC (HbA1c = 8.9 ± 2.1%). RESULTS: Overall, estradiol was significantly increased during the LF phase compared to M in both type 1 diabetes (Δestradiol = 75 ± 86 pg/mL) and controls (Δestradiol = 71 ± 76 pg/mL); however, an increase in TBARS was only observed in patients with type 1 diabetes (ΔTBARS = 3 ± 13 µM) compared to controls (ΔTBARS = 0 ± 4 µM). FMD was similar (p = 0.406) between groups at M. In addition, FMD increased significantly from M to the LF phase in controls (p = 0.024), whereas a decrease was observed in type 1 diabetes. FMD was greater (p = 0.015) in patients using HBC compared to those not on HBC, independent of menstrual cycle phase. CONCLUSION: Endogenous estradiol increases oxidative stress and contributes to endothelial dysfunction in women with diabetes. Additionally, HBC use appears to be beneficial to endothelial function in type 1 diabetes.

Muscle oxygen utilization and ventilatory parameters during exercise in people with cystic fibrosis: Role of HbA1c.

INTRODUCTION: Glycated hemoglobin can interfere with oxygen delivery and CO2 removal during exercise. Additionally, pancreatic insufficiency increases oxidative stress and exacerbates exercise intolerance in people with cystic fibrosis (PwCF). This investigation sought to test the hypotheses that elevated Hemoglobin A1c (HbA1c) can negatively affect exercise parameters in PwCF and that reductions in oxidative stress can improve tissue oxygenation in individuals with elevated HbA1c. METHODS: Twenty four PwCF were divided into two groups; normal HbA1c <5.7% (N-HbA1c) and elevated HbA1c >5.7% (E-HbA1c). A maximal exercise test was conducted to obtain peak oxygen uptake (VO2peak), VO2 at ventilatory threshold (VT), ventilatory parameters (VE/VCO2 slope and end-tidal CO2 (petCO2)). Near-Infrared Spectroscopy (NIRS) was used to assess muscle oxygenated/deoxygenated hemoglobin during exercise. A subset of individuals with E-HbA1cwere given an antioxidant cocktail (AOC) for 4 weeks to determine the effects on tissue oxygenation during exercise. RESULTS: A negative relationship between HbA1c and VO2peak at VT was observed (r = -0.511; p = 0.018). In addition, a positive relationship between HbA1c and VE/VCO2 slope (r = 0.587;p = 0.005) and a negative relationship between HbA1c and petCO2 at maximal exercise (r = -0.472;p = 0.031) was observed. N-HbA1c had greater VO2peak (p = 0.021), VO2 at VT (p = 0.004), petCO2 (p = 0.002), and lower VE/VCO2 slope (p = 0.004) compared with E-HbA1c. Muscle deoxygenated hemoglobin at VT was higher in N-HbA1c vs. E-HbA1c and 4 weeks of AOC improved skeletal muscle utilization of oxygen. CONCLUSION: Findings demonstrate that glycated hemoglobin may lead to tissue oxygenation impairment and ventilation inefficiency during exercise in PwCF. In addition, antioxidant supplementation may lead to improved tissue oxygenation during exercise.

Evidence of increased cardiovascular disease risk in left-handed individuals.

Background: Approximately 10% of the world is left-handed (LH). Research suggests that LH individuals may have shorter lifespans compared to right-handed (RH) individuals. LH individuals also appear to have more cardiovascular disease (CVD) related conditions like diabetes and cancer. Thus, the present study sought to test the hypothesis that vascular function and heart rate variability (HRV), both key indicators of CVD risk, would be lower in LH compared to RH individuals. Methods: Three hundred seventy-nine participants, 18-50 years old, were enrolled. Flow-mediated dilation (FMD), a bioassay of vascular endothelial function and standard deviation of R-R interval (SDNN), a parameter of HRV, were evaluated as indices of CVD risk. Data are reported as mean ± SD. Results: 12.1% of the participants were LH. No differences in demographics or clinical laboratory values were observed between groups, except high-density lipoprotein (HDL) was higher (p = 0.033) in RH. FMD was significantly (p = 0.043) lower in LH (6.1% ± 3.2%) compared to RH (7.6% ± 3.8%), independent of age, sex, race, BMI, and HDL. Total power (p = 0.024) and low-frequency power (p = 0.003) were lower in LH compared to RH. Additionally, SDNN was lower (p = 0.041) in LH (47.4 ± 18.8 ms) compared to RH (54.7 ± 22.3 ms). A negative correlation between FMD and mean arterial pressure (r = -0.517; p < 0.001) was observed in LH; no relationships were observed in RH (all p > 0.05). Conclusion: Vascular endothelial function and HRV are lower in LH compared to RH. In addition, relationships between FMD and traditional CVD risk factors were only observed in LH. These data support an increased risk of CVD in LH.

The Link Between Childhood Adversity and Cardiovascular Disease Risk: Role of Cerebral and Systemic Vasculature.

Adverse childhood experiences (ACEs) are traumatic events during the first years of life that are associated with a higher risk of developing cardiovascular disease (CVD) during adulthood. The medial prefrontal cortex (mPFC) is a core region in the brain that modulates emotions and is directly involved in the cardiovascular response to stress by increasing vascular resistance. In the present study we examined the relationship between ACEs, mPFC and peripheral vascular function. Forty-five, adults (33±5 yrs.) participated in the present study to evaluate cerebral hemodynamics and peripheral vascular function. The impact of adverse experiences was evaluated through the ACE questionnaire. Among those that experienced ACEs (ACE group, n = 22), there was a significantly (P < 0.001) reduced activation of the mPFC as well as greater peripheral vascular resistance observed in the small (P ≤ 0.035), conduit (P ≤ 0.042) and large (P ≤ 0.001) blood vessels, when compared to those that did not report ACEs (Control group, n = 23). In addition, relationships between the number of ACEs and mPFC activation (rs = -0.428; P = 0.003) and peripheral vascular function (rs ≤ -0.373; P ≤ 0.009) were observed. Findings from the present study support that adults who experienced ACEs exhibit a reduced activation of the mPFC along with systemic vascular dysfunction. In addition, individuals exposed to more childhood traumatic events exhibited a progressively greater inactivation of the mPFC and an increased peripheral vasoconstriction in a dose-dependent manner. These findings provide novel insights into the potential role that the brain and the peripheral vasculature may have in connecting adverse childhood events to the increased risk of CVD.

Whole body vibration elicits differential immune and metabolic responses in obese and normal weight individuals.

Traditional aerobic exercise reduces the risk of developing chronic diseases by inducing immune, metabolic, and myokine responses. Following traditional exercise, both the magnitude and time-course of these beneficial responses are different between obese compared to normal weight individuals. Although obesity may affect the ability to engage in traditional exercise, whole body vibration (WBV) has emerged as a more tolerable form of exercise . The impact of WBV on immune, metabolic, and myokine responses as well as differences between normal weight and obese individuals, however, is unknown. Purpose: To determine if WBV elicits differential magnitudes and time-courses of immune, metabolic, and myokine responses between obese and normal weight individuals. Methods: 21 participants [Obese (OB): n = 11, Age: 33 ±â€¯4 y, percent body fat (%BF): 39.1 ±â€¯2.4% & Normal weight (NW) n = 10, Age: 28 ±â€¯8 y, %BF: 17.4 ±â€¯2.1%] engaged in 10 cycles of WBV exercise [1 cycle = 1 min of vibration followed by 30 s of rest]. Blood samples were collected pre-WBV (PRE), immediately (POST), 3 h (3H), and 24 h (24H) post-WBV and analyzed for leukocytes, insulin, glucose, and myokines (IL-6, decorin, myostatin). Results: The peak (3H) percent change in neutrophil counts (OB: 13.9 ±â€¯17.4 vs. NW: 47.2 ±â€¯6.2%Δ; p = 0.007) was different between groups. The percent change in neutrophil percentages was increased in NW (POST: -1.6 ±â€¯2.0 vs. 3H: 13.0 ±â€¯7.2%Δ, p = 0.019) but not OB (p > 0.05). HOMA ß-cell function was increased at 24H (PRE: 83.4 ±â€¯5.4 vs. 24H: 131.0 ±â€¯14.1%; p = 0.013) in NW and was not altered in OB (p > 0.05). PRE IL-6 was greater in OB compared to NW (OB: 2.7 ±â€¯0.6 vs. NW: 0.6 ±â€¯0.1 pg/mL; p = 0.011); however, the percent change from PRE to peak (3H) was greater in NW (OB: 148.1 ±â€¯47.9 vs. NW: 1277.9 ±â€¯597.6 %Δ; p = 0.035). Creatine kinase, decorin, and myostatin were not significantly altered in either group (p > 0.05). Conclusion: Taken together, these data suggest that acute whole body vibration elicits favorable immune, metabolic, and myokine responses and that these responses differ between obese and normal weight individuals.

Assessment of endothelial function is reproducible in patients with cystic fibrosis.

BACKGROUND: New treatments have improved life-expectancy in patients with cystic fibrosis (CF); however, cardiovascular health remains an area of concern in this population. Flow-mediated dilation (FMD), a non-invasive assessment of vascular endothelial function that predicts future cardiovascular disease and events, is attenuated in patients with CF compared to controls. The reproducibility of FMD in CF; however, has yet to be evaluated. Thus, this study sought to examine the within-day, between-day, and between-month reproducibility of FMD in patients with CF. METHODS: Pulmonary function, baseline diameter (cm), peak diameter (cm), and FMD(%) were assessed 5 times (sessions A-E) over four visits in 13 patients with CF (six males, seven females, age range: 13-43 years old; mean forced expiratory volume in 1 s = 71% predicted). Sessions A and B (within-day), C (between-day), and D and E (between-month) were separated by 3 h, at least 10 days, and ~3 months, respectively. Reproducibility was assessed by: (1) paired t-tests, (2) coefficients of variation (CV), (3) CV prime, (4) Pearson's correlation (r), (5) intra-class correlation coefficient, and (6) Bland-Altman plots. Five acceptable parameters were required to determine reproducibility. RESULTS: Pulmonary function was stable throughout all visits. FMD(%) and baseline diameter (cm) satisfied all six reproducibility criteria for within-day, while peak diameter (cm) met five of six criteria. All six reproducibility criteria were met for all between-day and between-month assessments. CONCLUSION: The present study provides evidence that endothelial function assessed by FMD is reproducible in patients with CF not only within-day, but also between-day and between-month.