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Verceles A.C.,University of Maryland College Park | Koldobskiy D.,Life Bridge Health | Goldberg A.P.,University of Maryland College Park | Goldberg A.P.,University of Maryland, Baltimore | And 3 more authors.
Respiratory Care | Year: 2015

BACKGROUND: In this study, we examined the association between 25-hydroxyvitamin D (25(OH)D) concentration and successful weaning from mechanical ventilation in a cohort of ICU survivors requiring prolonged mechanical ventilation. METHODS: This was a retrospective cohort study of ICU survivors admitted to a long-term acute care hospital. Demographic data were extracted from medical records, including 25(OH)D concentrations drawn on admission. Subjects were divided into 2 groups based on their 25(OH)D concentrations (deficient, < 20 ng/mL; not deficient, ≥ 20 ng/mL), and associations between 25(OH)D concentration and successful weaning were calculated. RESULTS: A total of 183 subjects were studied. A high prevalence of 25(OH)D deficiency was found (61%, 111/183). No association was found between 25(OH)D concentration and weaning from mechanical ventilation. Increased comorbidity burden (Charlson comorbidity index) was associated with decreased odds of weaning (odds ratio of 0.50, 95% CI 0.25– 0.99, P =.05). CONCLUSIONS: Vitamin D deficiency is common in ICU survivors requiring prolonged mechanical ventilation. Surprisingly, there was no significant relationship between 25(OH)D concentration and successful weaning. This finding may be due to the low 25(OH)D concentrations seen in our subjects. Given what is known about vitamin D and lung function and given the low vitamin D concentrations seen in patients requiring long-term ventilatory support, interventional studies assessing the effects of 25(OH)D supplementation in these patients are needed. © 2015 Daedalus Enterprises.

Prior S.J.,University of Maryland Baltimore County | Prior S.J.,Baltimore Veterans Affairs Geriatric Research | Jenkins N.T.,University of Maryland University College | Brandauer J.,Gettysburg College | And 2 more authors.
Metabolism: Clinical and Experimental | Year: 2012

Insulin-like growth factor binding protein-1 (IGFBP-1) has metabolic effects throughout the body, and its expression is regulated in part by insulin. Circulating IGFBP-1 predicts development of cardiometabolic diseases in longitudinal studies, and low IGFBP-1 concentrations are associated with insulin resistance and consumption of a high-fat diet. Because of the favorable metabolic effects of regular aerobic exercise, we hypothesized that aerobic exercise training would increase plasma IGFBP-1 concentrations and attenuate the reduction in IGFBP-1 after a high-fat meal. Ten overweight (body mass index = 28.7 ± 0.9 kg/m 2), older (61 ± 2 years) men and women underwent high-fat feeding and oral glucose tolerance tests at baseline and after 6 months of aerobic exercise training. In response to aerobic exercise training, subjects increased cardiorespiratory fitness by 13% (P <.05) and insulin sensitivity index by 28% (P <.05). Basal plasma concentrations of IGFBP-1 increased by 41% after aerobic exercise training (P <.05). The insulin response to an oral glucose tolerance test was a significant predictor of fasting plasma IGFBP-1 concentrations at baseline and after exercise training (P =.02). In response to the high-fat meal at baseline, plasma IGFBP-1 concentrations decreased by 58% (P <.001); a 61% decrease to similar postprandial concentrations was observed after exercise training (P <.001). Plasma insulin response to the high-fat meal was inversely associated with postprandial IGFBP-1 concentrations at baseline and after exercise training (P =.06 and P <.05, respectively). Although aerobic exercise training did not attenuate the response to a high-fat meal, the increase in IGFBP-1 concentrations after exercise training may be one mechanism by which exercise reduces risk for cardiometabolic diseases in older adults. © 2012 Elsevier Inc. All rights reserved.

Jenkins N.T.,University of Maryland University College | Landers R.Q.,University of Maryland University College | Prior S.J.,University of Maryland Baltimore County | Prior S.J.,Baltimore Veterans Affairs Geriatric Research | And 3 more authors.
Journal of Applied Physiology | Year: 2011

We investigated the influence of acute and chronic endurance exercise on levels of intracellular nitric oxide (NO), superoxide (O 2 -), and expression of genes regulating the balance between these free radicals in CD34 - and CD34 + peripheral blood mononuclear cells (PBMCs; isolated by immunomagnetic cell separation). Blood samples were obtained from age- and body mass index (BMI)-matched endurance-trained (n = 10) and sedentary (n = 10) men before and after 30 min of exercise at 75% maximal oxygen uptake (VO 2max). Baseline levels of intracellular NO (measured by DAF-FM diacetate) and O 2 - (measured by dihydroethidium) were 26% (P <0.05) and 10% (P <0.05) higher, respectively, in CD34 - PBMCs from the sedentary group compared with the endurance-trained group. CD34 + PBMCs from the sedentary group at baseline had twofold greater inducible nitric oxide synthase (iNOS) mRNA and 50% lower endothelial NOS (eNOS) mRNA levels compared with the trained group (P < 0.05). The baseline group difference in O 2 - was eliminated by acute exercise. Experiments with apocynin indicated that the training-related difference in O 2 - levels was explained by increased NADPH oxidase activity in the sedentary state. mRNA levels of additional angiogenic and antioxidant genes were consistent with a more angiogenic profile in CD34 -cells of trained subjects. CD34 + PBMCs, examined for exploratory purposes, also displayed a more angiogenic mRNA profile in trained subjects, with vascular endothelial growth factor (VEGF) and eNOS being more highly expressed in trained subjects. Overall, our data suggest an association between the sedentary state and increased nitro-oxidative stress in CD34 +cells. © 2011 by the American Physiological Society.

Prior S.J.,University of Maryland Baltimore County | Prior S.J.,Baltimore Veterans Affairs Geriatric Research | Ryan A.S.,University of Maryland Baltimore County | Ryan A.S.,Baltimore Veterans Affairs Geriatric Research
Diabetes/Metabolism Research and Reviews | Year: 2013

Background: Reduced density of capillaries in skeletal muscle can limit insulin, glucose, and oxygen supply to the muscle, thereby contributing to worsening metabolism in older adults. The lower skeletal muscle capillarization in impaired glucose tolerance (IGT) may partially be due to circulating angiogenic cell dysfunction. Circulating angiogenic cells maintain the vasculature and promote angiogenesis, but circulating angiogenic cell number and function may be reduced in IGT. The goal of this study was to determine whether the clonogenic potential of circulating angiogenic cells is lower in IGT compared with normal-glucose-tolerant (NGT) controls and is associated with skeletal muscle capillarization. Methods: Glucose tolerance, endothelial cell colony-forming unit (CFU-EC) number, and vastus lateralis capillary density were measured in sedentary, older (62±1years, mean±SEM) men and women with NGT (n=16) and IGT (n=12). Results: Adults with IGT had 43% lower CFU-EC number (11.4±2.3 versus 20.1±2.0 colonies, p<0.01) and 12% lower capillary density (291±11 versus 330±9 capillaries/mm2, p<0.01) compared with those with NGT. In regression analyses, CFU-EC number inversely correlated with 120-min postprandial glucose in all subjects (r=-0.47, p<0.05), and capillary density was directly associated with CFU-EC number (r=0.53, p<0.05). Conclusions: We conclude that the clonogenic potential of circulating angiogenic cells is lower in sedentary older adults with IGT and is associated with lower skeletal muscle capillarization. Low circulating angiogenic cell clonogenic potential in IGT suggests a state of impaired angiogenesis occurring prior to overt type 2 diabetes that may mediate early microvascular changes in the development and progression of IGT to type 2 diabetes. © 2013.

Prior S.J.,Baltimore Veterans Affairs Geriatric Research | Prior S.J.,University of Maryland Baltimore County | Ryan A.S.,Baltimore Veterans Affairs Geriatric Research | Ryan A.S.,University of Maryland Baltimore County | And 4 more authors.
Obesity | Year: 2014

Objective People with type 2 diabetes have reduced cardiorespiratory fitness and metabolic impairments that are linked to obesity and often occur prior to the development of type 2 diabetes. We hypothesized that obese, older adults with impaired glucose tolerance (IGT) have lower ability to shift from fat to carbohydrate oxidation when transitioning from rest to submaximal exercise than normal glucose tolerant (NGT) controls. Design and Methods Glucose tolerance, body composition, and substrate oxidation (measured by RER:respiratory exchange ratio) during submaximal exercise (50% and 60% VO 2max) and insulin infusion (3-hour hyperinsulinemic-euglycemic clamp) were assessed in 23 sedentary, overweight-obese, older men and women. Results Obese subjects with NGT (n = 13) and IGT (n = 10) had similar resting RER, but during submaximal exercise those with IGT had a lower RER and less transition to carbohydrate oxidation than the NGT group (P < 0.05). The IGT group also oxidized less carbohydrate during insulin infusion than NGT (P < 0.05). RER at each exercise intensity independently correlated with120-minute postprandial glucose (r = -0.54 to -0.58, P < 0.05), but not with body composition, VO2max, or RER during insulin infusion. Conclusions Obese, older adults have metabolic inflexibility during exercise that is associated with the degree of glucose intolerance independent of age and body composition. Copyright © 2013 This article is a US government work and, as such, is in the public domain in the United States of America.

Prior S.J.,University of Maryland Baltimore County | Prior S.J.,Baltimore Veterans Affairs Geriatric Research | Prior S.J.,Baltimore Medical Center | Ryan A.S.,University of Maryland Baltimore County | And 9 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2016

Background: Skeletal muscle capillary rarefaction limits the transcapillary transport of nutrients and oxygen to muscle and may contribute to sarcopenia and functional impairment in older adults. We tested the hypothesis that skeletal muscle capillarization and exercise capacity (VO2max) are lower in sarcopenic than in nonsarcopenic older adults and that the degree of sarcopenia is related to lower skeletal muscle capillarization. Methods: Body composition, VO2max, and vastus lateralis capillarization were determined in 76 middle-aged and older men and women (age = 61±1 years, body mass index [BMI] = 30.7±0.5kg/m2 [mean ± SEM]). Participants were classified as sarcopenic if appendicular lean mass divided by BMI (ALMBMI) was less than 0.789 for men or less than 0.512 for women. Results: Sarcopenic subjects (ALMBMI = 0.65±0.04, n = 16) had 20% lower capillary-to-fiber ratio, as well as 13% and 15% lower VO2max expressed as mL/kg/min or L/min, respectively, compared with sex-, race-, and age-matched participants without sarcopenia (ALMBMI = 0.81±0.05, n = 16; p <. 05). In all 76 subjects, ALMBMI, thigh muscle cross-sectional area, and VO2max correlated directly with capillarization (r =. 30-.37, p ≤. 05), after accounting for age, sex, and race. Conclusions: These findings suggest that low skeletal muscle capillarization is one factor that may contribute to sarcopenia and reduced exercise capacity in older adults by limiting diffusion of substrates, oxygen, hormones, and nutrients. Strategies to prevent the aging-related decline in skeletal muscle capillarization may help to prevent or slow the progression of sarcopenia and its associated functional declines in generally healthy older adults. © 2016 The Author. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.

Prior S.J.,University of Maryland Baltimore County | Prior S.J.,Baltimore Veterans Affairs Geriatric Research | Goldberg A.P.,University of Maryland Baltimore County | Goldberg A.P.,Baltimore Veterans Affairs Geriatric Research | And 2 more authors.
Obesity | Year: 2011

The Β 2-adrenergic receptor (ADRB2) mediates obesity, cardiorespiratory fitness, and insulin resistance. We examined the hypothesis that ADRB2 Arg16Gly-Gln27Glu haplotype is associated with body composition, glucose tolerance, and insulin sensitivity in obese, postmenopausal women. Obese (35% body fat), postmenopausal (age 45-75 years) women (n = 123) underwent genotyping, dual-energy X-ray absorptiometry, and computed tomography scans, exercise testing (VO 2max), 2-h oral glucose tolerance tests (OGTTs), and hyperinsulinemic-euglycemic clamps (80mU/m 2 /min). Analysis of covariance (ANCOVA) tested for differences among haplotypes, with race, % body fat, and VO 2max as covariates. We found that ADRB2 haplotype was independently associated with % body fat, abdominal fat distribution, VO 2max, insulin sensitivity (M/ΔInsulin), and glucose tolerance (ANOVA, P 0.05 for all). Women homozygous for Gly16-Gln27 haplotype had the highest % body fat (52.7 1.9%), high abdominal fat, low M/ΔInsulin (0.49 0.08mg/kg/min/pmol/ l/10 2), and impaired glucose tolerance (IGT) during an OGTT (G 120 = 10.2 0.9mmol/l). Women homozygous for Gly16-Glu27 haplotype also had low M/ΔInsulin (0.51 0.05mg/kg/min/pmol/l/10 2) and IGT (G 120 = 8.2 0.7mmol/l). Subjects with Arg16-Gln27/Gly16-Gln27 haplotype combination had the highest VO 2max (1.84 0.07l/min) and M/ΔInsulin (0.7 0.04mg/kg/min/pmol/l/10 2), and normal glucose tolerance (G 120 = 6.4 0.4mmol/l), despite being obese. These data show associations of the ADRB2 Arg16Gly-Gln27Glu haplotype with VO 2max and body composition, and an independent association with glucose metabolism, which persists after controlling for body composition and fitness. This suggests that ADRB2 haplotypes may mediate insulin action, glucose tolerance, and potentially risk for type 2 diabetes mellitus (T2DM) in obese, postmenopausal women. © 2010 The Obesity Society.

Jenkins N.T.,University of Maryland College Park | Landers R.Q.,University of Maryland College Park | Thakkar S.R.,Temple University | Fan X.,Temple University | And 5 more authors.
Journal of Physiology | Year: 2011

We hypothesized that prior exercise would prevent postprandial lipaemia (PPL)-induced increases in intracellular reactive oxygen species (ROS) in three distinct circulating angiogenic cell (CAC) subpopulations. CD34 +, CD31 +/CD14 -/CD34 -, and CD31 +/CD14 +/CD34 - CACs were isolated from blood samples obtained from 10 healthy men before and 4 h after ingesting a high fat meal with or without ∼50 min of prior endurance exercise. Significant PPL-induced increases in ROS production in both sets of CD31 + cells were abolished by prior exercise. Experimental ex vivo inhibition of NADPH oxidase activity and mitochondrial ROS production indicated that mitochondria were the primary source of PPL-induced oxidative stress. The attenuated increases in ROS with prior exercise were associated with increased antioxidant gene expression in CD31 +/CD14 -/CD34 - cells and reduced intracellular lipid uptake in CD31 +/CD14 +/CD34 - cells. These findings were associated with systemic cardiovascular benefits of exercise, as serum triglyceride, oxidized low density lipoprotein-cholesterol, and plasma endothelial microparticle concentrations were lower in the prior exercise trial than the control trial. In conclusion, prior exercise completely prevents PPL-induced increases in ROS in CD31 +/CD14 -/CD34 - and CD31 +/CD14 +/CD34 - cells. The mechanisms underlying the effects of exercise on CAC function appear to vary among specific CAC types. © 2011 The Authors. Journal compilation © 2011 The Physiological Society.

Prior S.J.,University of Maryland Baltimore County | Prior S.J.,Baltimore Veterans Affairs Geriatric Research | Blumenthal J.B.,University of Maryland Baltimore County | Blumenthal J.B.,Baltimore Veterans Affairs Geriatric Research | And 6 more authors.
Diabetes Care | Year: 2014

OBJECTIVE: Transcapillary transport of insulin is one determinant of glucose uptake by skeletal muscle; thus, a reduction in capillary density (CD) may worsen insulin sensitivity. Skeletal muscle CD is lower in older adults with impaired glucose tolerance (IGT) compared with those with normal glucose tolerance and may be modifiable through aerobic exercise training and weight loss (AEX+WL). We tested the hypothesis that 6-month AEX+WL would increase CD to improve insulin sensitivity and glucose tolerance in older adults with IGT. RESEARCH DESIGN AND METHODS: Sixteen sedentary, overweight-obese (BMI 27-35 kg/m2), older (63 ± 2 years) men and women with IGT underwent hyperinsulinemic-euglycemic clamps to measure insulin sensitivity, oral glucose tolerance tests, exercise and body composition testing, and vastus lateralis muscle biopsies to determine CD before and after 6-month AEX+WL. RESULTS: Insulin sensitivity (M) and 120-min postprandial glucose (G120) correlated with CD at baseline (r = 0.58 and r = -0.60, respectively, P < 0.05). AEX+WL increased maximal oxygen consumption (VO2max) 18% (P = 0.02) and reduced weight and fat mass 8% (P < 0.02). CD increased 15% (264 ± 11 vs. 304 ± 14 capillaries/mm2, P = 0.01), M increased 21% (42.4 ± 4.0 vs. 51.4 ± 4.3 μmol/kg FFM/min, P < 0.05), and G120 decreased 16% (9.35 ± 0.5 vs. 7.85 ± 0.5 mmol/L, P = 0.008) after AEX+WL. Regression analyses showed that the AEX+WL-induced increase in CD independently predicted the increase in M (r = 0.74, P < 0.01) as well as the decrease in G120 (r = -0.55, P < 0.05). CONCLUSIONS: Six-month AEX+WL increases skeletal muscle CD in older adults with IGT. This represents one mechanism by which AEX+WL improves insulin sensitivity in older adults with IGT. © 2014 by the American Diabetes Association.

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