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  • Ovid Technologies (Wolters Kluwer Health)  (68)
  • 1
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    Absence of Acute Inhibitory Effect of Insulin on Chylomicron Production in Type 2 Diabetes
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 32, No. 4 ( 2012-04), p. 1039-1044
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 32, No. 4 ( 2012-04), p. 1039-1044
    Abstract: Overproduction of intestinally derived apoB-48-containing triglyceride-rich lipoproteins (TRLs) (chylomicrons) has recently been described in type 2 diabetes, as is known for hepatic TRL-apoB-100 (very-low-density lipoprotein) production. Furthermore, insulin acutely inhibits both intestinal and hepatic TRL production, whereas this acute inhibitory effect on very-low-density lipoprotein production is blunted in type 2 diabetes. It is not currently known whether this acute effect on chylomicron production is similarly blunted in humans with type 2 diabetes. Methods and Results— We investigated the effect of acute hyperinsulinemia on TRL metabolism in 18 type 2 diabetic men using stable isotope methodology. Each subject underwent 1 control (saline infusion [SAL]) lipoprotein turnover study followed by a second study, under 1 of the 3 following clamp conditions: (1) hyperinsulinemic-euglycemic, (2) hyperinsulinemic-hyperglycemic, or (3) hyperinsulinemic-euglycemic plus intralipid and heparin. TRL-apoB-48 and TRL-apoB-100 production and clearance rates were not different between SAL and clamp and between the different clamp conditions, except for significantly lower TRL-apoB-100 clearance and production rates in hyperinsulinemic-euglycemic plus intralipid and heparin clamp compared with SAL. Conclusion— This is the first demonstration in individuals with type 2 diabetes that chylomicron production is resistant to the normal acute suppressive effect of insulin. This phenomenon may contribute to the highly prevalent dyslipidemia of type 2 diabetes and potentially to atherosclerosis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00950209.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/ATVBAHA.111.242073
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1494427-3
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  • 2
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    Effects of Intranasal Insulin on Triglyceride-Rich Lipoprotein Particle Production in Healthy Men
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 37, No. 9 ( 2017-09), p. 1776-1781
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. 9 ( 2017-09), p. 1776-1781
    Abstract: Insulin administered directly into the brain acutely suppresses hepatic glucose production and triglyceride-rich lipoprotein (TRL) secretion in rodents. In addition, intranasally administered insulin, which selectively raises cerebrospinal fluid insulin concentration, suppresses hepatic glucose production in humans; however, its effect on TRL secretion in humans has not previously been examined. In this study, we examined whether intranasal insulin, administered at a dose that has previously been shown to suppress hepatic glucose production, modulates TRL particle secretion by the liver and intestine in humans. Approach and Results— Nine healthy, normolipidemic, and normoglycemic men participated in a study consisting of 2 randomized study arms. Subjects received intranasal lispro insulin (40 IU) or placebo. Because intranasal insulin results in a rapid and transient increase in systemic insulin concentration after administration, we matched systemic insulin concentrations in the 2 study arms by infusing lispro insulin intravenously for 30 minutes together with intranasal placebo administration. Apo (apolipoprotein) B100–containing (hepatically derived) and apoB48-containing (intestinally derived) TRL lipoprotein particle turnover were measured for the ensuing 10 hours under pancreatic clamp conditions and constant fed state, using stable isotope enrichment techniques and multicompartmental modeling. Under these experimental conditions, no significant effects of intranasal insulin versus placebo on TRL apoB100 or B48 concentrations, fractional catabolic rates, or production rates were observed. Conclusions— Insulin delivered intranasally at a dose that has been shown to raise cerebrospinal fluid insulin concentration and suppress hepatic glucose production does not affect TRL particle production by the liver and intestine in healthy men. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT03141827.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/ATVBAHA.117.309705
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1494427-3
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  • 3
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    Hyperinsulinemia Is Associated With Increased Production Rate of Intestinal Apolipoprotein B-48–Containing Lipoproteins in Humans
    Ovid Technologies (Wolters Kluwer Health) ; 2006
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 26, No. 6 ( 2006-06), p. 1357-1363
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 26, No. 6 ( 2006-06), p. 1357-1363
    Abstract: In the present study, we investigated whether intestinal lipoprotein particle production rate is related to indices of insulin resistance in humans. ApoB-48–containing lipoprotein metabolism was examined in 14 nondiabetic men with a broad range of BMI and insulin sensitivity. We demonstrate that intestinal apoB-48–containing TRL production rate is increased in hyperinsulinemic, insulin-resistant humans.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/01.ATV.0000222015.76038.14
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2006
    detail.hit.zdb_id: 1494427-3
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  • 4
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    Effect of Atorvastatin on High-Density Lipoprotein Apolipoprotein A-I Production and Clearance in the New Zealand White Rabbit
    Ovid Technologies (Wolters Kluwer Health) ; 2002
    In:  Circulation Vol. 106, No. 23 ( 2002-12-03), p. 2955-2960
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 106, No. 23 ( 2002-12-03), p. 2955-2960
    Abstract: Background— HMG-CoA reductase inhibitors reduce the incidence of cardiovascular disease predominantly by their LDL-lowering effect. Recently, there has been great interest in the pleiotropic effects of statins, which appear to differ among the various agents in this class. Unlike other statins, atorvastatin exhibits a decline in its HDL-raising effect at higher doses in humans. Whether atorvastatin-mediated alterations in HDL turnover in vivo contribute to this effect has not previously been investigated. We therefore studied the effect of atorvastatin on HDL apolipoprotein (apo) A-I production and clearance in normolipidemic male New Zealand White rabbits. Methods and Results— Kinetic studies of HDL-apoA-I radiolabeled with 131 I were performed in chow-fed rabbits after 3 weeks of atorvastatin treatment of 5 mg · kg −1 · d −1 (n=7) versus placebo-treated rabbits (n=7). Our results showed a significantly ( P 〈 0.001) more rapid clearance (≈2-fold) of HDL apoA-I in atorvastatin-treated animals compared with the control group (0.121±0.012 versus 0.061±0.004 pools/h, respectively), accompanied by a lesser 48% increase in the apoA-I production rate (3.84±0.38 versus 2.59±0.41 mg · kg −1 · h −1 , P =0.06). Accordingly, plasma apoA-I levels in atorvastatin-treated animals declined significantly ( P 〈 0.05, n=8 animals) after 3 weeks of treatment (173.5±1.8 mg/dL) from baseline values. Conclusions— These data suggest that the effect on apoA-I levels observed with atorvastatin at higher drug doses in humans may be caused at least in part by enhanced HDL apoA-I catabolism, which is not entirely offset by a concomitant increase in apoA-I production. Whether this finding results from an effect of atorvastatin on HDL particle composition or on receptors involved in circulating HDL holoparticle clearance will require further study.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/01.CIR.0000038303.84249.4A
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2002
    detail.hit.zdb_id: 1466401-X
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  • 5
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    New Insights Into the Regulation of HDL Metabolism and Reverse Cholesterol Transport
    Ovid Technologies (Wolters Kluwer Health) ; 2005
    In:  Circulation Research Vol. 96, No. 12 ( 2005-06-24), p. 1221-1232
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 12 ( 2005-06-24), p. 1221-1232
    Abstract: The metabolism of high-density lipoproteins (HDL), which are inversely related to risk of atherosclerotic cardiovascular disease, involves a complex interplay of factors regulating HDL synthesis, intravascular remodeling, and catabolism. The individual lipid and apolipoprotein components of HDL are mostly assembled after secretion, are frequently exchanged with or transferred to other lipoproteins, are actively remodeled within the plasma compartment, and are often cleared separately from one another. HDL is believed to play a key role in the process of reverse cholesterol transport (RCT), in which it promotes the efflux of excess cholesterol from peripheral tissues and returns it to the liver for biliary excretion. This review will emphasize 3 major evolving themes regarding HDL metabolism and RCT. The first theme is that HDL is a universal plasma acceptor lipoprotein for cholesterol efflux from not only peripheral tissues but also hepatocytes, which are a major source of cholesterol efflux to HDL. Furthermore, although efflux of cholesterol from macrophages represents only a tiny fraction of overall cellular cholesterol efflux, it is the most important with regard to atherosclerosis, suggesting that it be specifically termed macrophage RCT. The second theme is the critical role that intravascular remodeling of HDL by lipid transfer factors, lipases, cell surface receptors, and non-HDL lipoproteins play in determining the ultimate metabolic fate of HDL and plasma HDL-c concentrations. The third theme is the growing appreciation that insulin resistance underlies the majority of cases of low HDL-c in humans and the mechanisms by which insulin resistance influences HDL metabolism. Progress in our understanding of HDL metabolism and macrophage reverse cholesterol transport will increase the likelihood of developing novel therapies to raise plasma HDL concentrations and promote macrophage RCT and in proving that these new therapeutic interventions prevent or cause regression of atherosclerosis in humans.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/01.RES.0000170946.56981.5c
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2005
    detail.hit.zdb_id: 1467838-X
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  • 6
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    Exenatide, a Glucagon-like Peptide-1 Receptor Agonist, Acutely Inhibits Intestinal Lipoprotein Production in Healthy Humans
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 32, No. 6 ( 2012-06), p. 1513-1519
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 32, No. 6 ( 2012-06), p. 1513-1519
    Abstract: Incretin-based therapies for the treatment of type 2 diabetes mellitus improve plasma lipid profiles and postprandial lipemia, but their exact mechanism of action remains unclear. Here, we examined the acute effect of the glucagon-like peptide-1 receptor agonist, exenatide, on intestinal and hepatic triglyceride-rich lipoprotein production and clearance in healthy humans. Methods and Results— Fifteen normolipidemic, normoglycemic men underwent 2 studies each (SC 10 μg exenatide versus placebo), 4 to 6 weeks apart, in random order, in which triglyceride-rich lipoprotein particle kinetics were examined with a primed, constant infusion of deuterated leucine and analyzed by multicompartmental modeling under pancreatic clamp conditions. A fed state was maintained during each study by infusing a high-fat, mixed macronutrient, liquid formula at a constant rate directly into the duodenum via a nasoduodenal tube. Exenatide significantly suppressed the plasma concentration and production rate of triglyceride-rich lipoprotein-apolipoprotein B-48, but not of triglyceride-rich lipoprotein-apolipoprotein B-100. Conclusions— These results suggest a possible direct effect of exenatide on intestinal lipoprotein particle production, independent of changes in weight gain and satiety as seen in long-term studies and independent of changes in gastric emptying. This finding expands our understanding of the effects of exenatide in metabolic regulation beyond its primary therapeutic role in regulation of glucose homeostasis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov , NCT01056549.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/ATVBAHA.112.246207
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1494427-3
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  • 7
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    Effects of Bariatric Surgery on Hepatic and Intestinal Lipoprotein Particle Metabolism in Obese, Nondiabetic Humans
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 34, No. 10 ( 2014-10), p. 2330-2337
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 10 ( 2014-10), p. 2330-2337
    Abstract: The dyslipidemia of obesity and other insulin-resistant states is characterized by the elevation of plasma triglyceride-rich lipoproteins (TRL) of both hepatic (apoB-100–containing very low-density lipoprotein) and intestinal (apoB-48–containing chylomicrons) origin. Bariatric surgery is a well-established and effective modality for the treatment of obesity and is associated with improvements in several metabolic abnormalities associated with obesity, including a reduction in plasma triglycerides. Here, we have investigated the effect of bariatric surgery on TRL metabolism. Approach and Results— Twenty-two nondiabetic, obese subjects undergoing bariatric surgery: sleeve gastrectomy (n=12) or gastric bypass (n=10) were studied. Each subject underwent 1 lipoprotein turnover study 1 month before surgery followed by a second study, 6 months after surgery, using established stable isotope enrichment methodology, in constant fed state. TRL-apoB-100 concentration was significantly reduced after sleeve gastrectomy, explained by a decrease ( P 〈 0.05) in TRL-apoB-100 production rate and an increase ( P 〈 0.05) in TRL-apoB-100 fractional catabolic rate. TRL-apoB-48 concentration was also significantly reduced after sleeve gastrectomy, explained by reduction in TRL-apoB-48 production rate ( P 〈 0.05). For gastric bypass, although TRL-apoB-100 concentration declined after surgery ( P 〈 0.01), without a significant decline in TRL-apoB-48, there was no significant change in either TRL-apoB-100 or TRL-apoB-48 production rate or fractional catabolic rate. The reduction in TRL-apoB-100 concentration was significantly associated with a reduction in plasma apoC-III in the pooled group of patients undergoing bariatric surgery. Conclusions— This is the first human lipoprotein kinetic study to explore the mechanism of improvement of TRL metabolism after bariatric surgery. These effects may contribute to the decrease of cardiovascular mortality after surgery. Clinical Trial Registration— URL: http://www.ClinicalTrials.gov . Unique identifier: NCT01277068.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/ATVBAHA.114.303849
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1494427-3
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  • 8
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    Identifying Potentially Avoidable Hospital Admissions From Canadian Long-Term Care Facilities
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Medical Care Vol. 47, No. 2 ( 2009-02), p. 250-254
    Details
    In: Medical Care, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. 2 ( 2009-02), p. 250-254
    Type of Medium: Online Resource
    ISSN: 0025-7079
    URL: Article
    DOI: 10.1097/MLR.0b013e3181847588
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
    detail.hit.zdb_id: 2045939-7
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  • 9
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    Hemodynamic Effects of Sacubitril-Valsartan Versus Enalapril in Patients With Heart Failure in the EVALUATE-HF Study : Effect Modification by Left Ventricular Ejection Fraction and Sex
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation: Heart Failure Vol. 14, No. 3 ( 2021-03)
    Details
    In: Circulation: Heart Failure, Ovid Technologies (Wolters Kluwer Health), Vol. 14, No. 3 ( 2021-03)
    Abstract: Treatment with sacubitril-valsartan reduces mortality and heart failure (HF) events in HF with reduced ejection fraction and may reduce HF hospitalization in women with HF with preserved ejection fraction. Methods: EVALUATE-HF randomized 464 participants (109 women) with HF with reduced ejection fraction to sacubitril-valsartan or enalapril for 12 weeks. Documented left ventricular ejection fraction (LVEF) ≤0.40 within the prior 12 months was required, although core laboratory LVEF 〉 0.40 was permitted. Assessments of aortic stiffness (pulse pressure and characteristic impedance, Z c ) were performed at baseline and at trough and 4 hours postdose at weeks 4 and 12. Results: In models of change from baseline adjusted for baseline value, treatment with sacubitril-valsartan produced greater overall reductions in mean arterial pressure (treatment group difference, −3.0±0.8 mm Hg, P 〈 0.001) and pulse pressure (−3.0±0.8 mm Hg, P 〈 0.001). Postdose reductions in Z c were greater in the sacubitril-valsartan group (−16±6 dyne×second/cm 5 , P =0.012). Post hoc analyses found evidence of effect modification by LVEF (interaction P =0.036). With LVEF 〈 0.40, postdose reductions in Z c were greater in the sacubitril-valsartan group (trough, −3±8 dyne×second/cm 5 versus post-dose, −17±8 dyne×second/cm 5 ; interaction P =0.024) with no sex difference (treatment×sex interaction, P =0.3). With LVEF≥0.40, treatment with sacubitril-valsartan was associated with greater overall reductions in Z c in women (women, −80±21 dyne×second/cm 5 versus men, −20±13 dyne×second/cm 5 ; interaction P =0.019). Conclusions: In prespecified analyses that include pre- and postdose assessments at 4 and 12 weeks, treatment with sacubitril-valsartan was associated with greater postdose reductions in aortic Z c . In a post hoc analysis, sacubitril-valsartan was associated with sustained reductions in Z c in women with LVEF≥0.40. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT02874794.
    Type of Medium: Online Resource
    ISSN: 1941-3289 , 1941-3297
    URL: Article
    DOI: 10.1161/CIRCHEARTFAILURE.120.007891
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2428100-1
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  • 10
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    Abstract 003: Neighborhood Characteristics And Arterial Stiffness Among Black Adults - Results From The Jackson Heart Study & Morehouse Emory Center For Health Equity
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 143, No. Suppl_1 ( 2021-05-25)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 143, No. Suppl_1 ( 2021-05-25)
    Abstract: Introduction: Poor quality neighborhoods are independent risk factors for cardiovascular disease (CVD) but are understudied in Blacks, who face large CVD health disparities. Arterial stiffness (AS) precedes development of hypertension and adverse CVD events but the effect of neighborhood on AS among Blacks remain unknown. Objective: We compared the association between neighborhood environment and AS among Blacks in Jackson, MS and Atlanta, GA. Methods: We studied 1592 Blacks (age 58 ± 10, 38% male) living in Jackson, MS from the Jackson Heart Study (JHS) and 451 Blacks (age 53 ± 10, 39% male) living in Atlanta, GA from the Morehouse/Emory Center for Health Equity (MECA) study, without known CVD. Neighborhood problems (includes measures of aesthetic quality, walking environment, food access), social cohesion (includes activity with neighbors), and violence/safety were assessed using validated questionnaires. AS was measured as pulse wave velocity (PWV) using MRI in JHS and as PWV and augmentation index (AIx) using applanation tonometry (Sphygmocor Inc) in MECA. Multivariable linear regression models were used to examine the association between neighborhood characteristics and AS, adjusting for potential confounders. Results: Improved social characteristics, measured as social cohesion in JHS (β = -0.32 [-0.63, - 0.02], p=0.04) and activity with neighbors (β = -0.23 [-0.40, - 0.05] p=0.01) in MECA, were associated with lower PWV in both cohorts and lower AIx (β = -1.74 [-2.92, - 0.56], p=0.004) in MECA, after adjustment for CVD risk factors and income. Additionally, in MECA better food access (β = -1.18 [-2.35, - 0.01] , p=0.05) was associated with lower AIx, and in JHS, lower neighborhood problems (β = -0.33 [-0.64, - 0.02], p=0.04) and lower violence (β = -0.30 [-0.61, 0.002] , p=0.05) were associated with lower PWV (Fig). Conclusion: Neighborhood social characteristics show an independent association with vascular health of Blacks, findings that were reproducible in two distinct American cities.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.143.suppl_1.003
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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