276 results on '"Erkelens DW"'
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2. Procoagulant Activity of Endothelial Cells after Infection with Respiratory Viruses
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John J. M. Bouwman, de Groot Ph, Erkelens Dw, Frank L.J. Visseren, K.P. Bouter, and R. J. A. Diepersloot
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Endothelium ,business.industry ,viruses ,Hematology ,Virology ,Virus ,Endothelial stem cell ,Tissue factor ,medicine.anatomical_structure ,Viral envelope ,Cell culture ,Prothrombinase ,medicine ,business ,Blood coagulation test - Abstract
SummaryInfluenza virus epidemics are associated with excess mortality due to cardiovascular diseases. There are several case reports of excessive coagulation during generalised influenza virus infection. In this study, we demonstrate the ability of respiratory viruses (influenza A, influenza B, parainfluenza-1, respiratory syncytial virus, adenovirus, cytomegalovirus) to infect lung fibroblasts and human umbilical vein endothelial cells in culture. All viral pathogens induced procoagulant activity in infected endothelial cells, as determined in a one-stage clotting assay, by causing an average 55% reduction in the clotting time. When factor VII deficient plasma was used clotting time was not reduced. The induction of procoagulant activity was associated with a 4- to 5-fold increase in the expression of tissue factor, as measured by the generation of factor Xa. Both experiments indicate that the procoagulant activity of endothelial cells in response to infection with respiratory viruses is caused by upregulation of the extrinsic pathway. Although both enveloped viruses and a non-enveloped virus (adenovirus) induced procoagulant activity in endothelial cells by stimulating tissue factor expression, the role of the viral envelope in the assembly of the prothrombinase complex remains uncertain.We conclude that both enveloped and non-enveloped respiratory viruses are capable of infecting cultured human endothelial cells and causing a shift from anticoagulant to procoagulant activity associated with the induction of tissue factor expression.
- Published
- 2000
3. Acute Exogenous Elevation of Plasma Free Fatty Acids Does Not Influence the Plasma Magnesium Concentration
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Bianchi R, van Rijn Hj, Erkelens Dw, and de Valk Hw
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Adult ,Male ,Fat Emulsions, Intravenous ,medicine.medical_specialty ,medicine.medical_treatment ,Clinical Biochemistry ,chemistry.chemical_element ,Endogeny ,Fatty Acids, Nonesterified ,chemistry.chemical_compound ,Reference Values ,Internal medicine ,Blood plasma ,Mole ,medicine ,Humans ,Lipolysis ,Magnesium ,Saline ,Triglycerides ,chemistry.chemical_classification ,Triglyceride ,Chemistry ,Biochemistry (medical) ,Fatty acid ,General Medicine ,Endocrinology - Abstract
Objective: Plasma non-esterified (free) fatty acid concentrations rise as a consequence of stimulated endogenous lipolysis and are inversely related to the plasma magnesium concentration when plasma adrenaline concentration is increased. The aim of the study was to test whether high plasma non-esterified fatty acid concentration after infusion of non-esterified fatty acids decreases plasma magnesium concentration. Methods: Twelve healthy subjects received 500 ml Intralipid or saline in a randomised, cross-over, double-blind design. Infusion of Intralipid results in an isolated elevation of plasma non-esterified fatty acid concentration. Plasma magnesium concentration was determined at baseline and every 30 minutes; plasma nonesterified fatty acid and triglyceride concentrations at baseline and after 120 minutes. Results: Initial plasma magnesium, non-esterified fatty acid, and triglyceride concentrations were similar in both groups. A significant increase in plasma non-esterified fatty acids (2.42 ± 0.96 mmol/l vs 0.58 ± 0.23 mmol/l, p = 0.00013) and triglyceride (median and 95th percentile 5.36 (7.35) mmol/l vs 1.18 (1.92) mmol/l, p = 0.003) concentrations was seen with Intralipid. Plasma magnesium concentration increased significantly after Intralipid (0.89 ± 0.09 mmol/l vs 0.81 ± 0.06 mmol/l, p = 0.007). No significant changes were seen with saline. A positive association was found between the change in plasma magnesium and triglyceride concentrations (r = 0.85, p = 0.001). Conclusion: Acute infusion of non-esterified fatty acids from an exogenous source does not result in a fall in plasma magnesium concentration, indicating that the circulating non-esterified fatty acids play no part in a decrease in plasma magnesium concentration. The high circulating non-esterified fatty acid levels and the fall in plasma magnesium concentration are both a consequence of intracellular lipolysis.
- Published
- 1998
4. The cholesterol century
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Erkelens Dw
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chemistry.chemical_compound ,chemistry ,business.industry ,Cholesterol ,Anticholesteremic Agents ,Internal Medicine ,Medicine ,Arteriosclerosis ,business ,Bioinformatics ,medicine.disease - Published
- 1997
5. Hartafwijkingen
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Meijboom, FJ (Folkert), Roos - Hesselink, Jolien, Bogers, Ad, Kimpen, JLL, Boers, GHJ, Erkelens, DW, Lammers, JWJ, Cardiology, and Cardiothoracic Surgery
- Published
- 2004
6. Infectieziekten
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van der Meer, JWM, Gyssens, ICJ (Inge), van Meinders, AE, Boogaerts, MA, Erkelens, DW, Vermeij, P, and Medical Microbiology & Infectious Diseases
- Published
- 2003
7. Gender differences in diurnal triglyceridemia in lean and overweight subjects
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Castro Cabezas M, Halkes Cj, van Wijk Jp, and Erkelens Dw
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Adult ,Male ,medicine.medical_specialty ,Waist ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Overweight ,Fasting insulin ,chemistry.chemical_compound ,Insulin resistance ,Internal medicine ,Abdomen ,medicine ,Humans ,Insulin ,Obesity ,Triglycerides ,Sex Characteristics ,Nutrition and Dietetics ,Triglyceride ,business.industry ,nutritional and metabolic diseases ,Fasting ,Middle Aged ,medicine.disease ,Postprandial Period ,Circadian Rhythm ,Endocrinology ,Postprandial ,chemistry ,Adipose Tissue ,Area Under Curve ,Body Constitution ,Female ,medicine.symptom ,Insulin Resistance ,business ,Body mass index ,Lipoprotein - Abstract
AIMS: Increased fasting and postprandial triglyceridemia is one of the cardiovascular risk factors for patients with insulin resistance. Since triglyceride (TG) metabolism largely depends on gender, we have investigated diurnal TG changes in patients with and without overweight, focusing on gender differences. METHODS: Twenty-two males and 22 females with overweight (mean body mass index (BMI) 28.0±2.3 kg/m2) measured capillary TG concentrations at six fixed time points on three different days. Diurnal TG profiles were calculated as area under the capillary TG curves (TGc-AUCs). The control group consisted of 24 males and 21 females who were not overweight (mean BMI 22.4±1.5 kg/m2). Biochemical and anthropometric parameters associated with insulin resistance were measured. RESULTS: Lean males and lean females had comparable fasting insulin levels (6.9±2.6 and 8.1±4.7 mU/l, respectively), but females had a more favorable fasting lipoprotein profile when compared to males. Diurnal TG profiles were lower in lean females than in lean males (16.9±4.3 vs 20.3±5.7 mMh, respectively, P
- Published
- 2000
8. Interleukin-6 production by endothelial cells after infection with influenza virus and cytomegalovirus
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Frank L.J. Visseren, K.P. Bouter, M.S.A. Verkerk, Erkelens Dw, and R. J. A. Diepersloot
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Human cytomegalovirus ,Umbilical Veins ,medicine.medical_treatment ,Orthomyxoviridae ,Hemagglutinin (influenza) ,Cytomegalovirus ,medicine.disease_cause ,Herpesviridae ,Virus ,Pathology and Forensic Medicine ,Proinflammatory cytokine ,medicine ,Humans ,Microscopy, Phase-Contrast ,Cells, Cultured ,biology ,L-Lactate Dehydrogenase ,Interleukin-6 ,virus diseases ,Interleukin ,General Medicine ,medicine.disease ,biology.organism_classification ,Virology ,Cytokine ,Influenza A virus ,Immunology ,biology.protein ,Endothelium, Vascular - Abstract
Inflammation plays a role in the pathogenesis of cardiovascular diseases. Viruses may be a cause of chronic inflammation, and both influenza virus and CMV have been associated with cardiovascular diseases. IL-6, a proinflammatory cytokine with antiviral effects, has a pivotal role in the immune response, and under pathologic conditions, prohemostatic effects of IL-6 could lead to pathologic thrombosis and vascular plaque instability. To investigate this role of IL-6, we measured the production of IL-6 by human endothelial cells after infection with influenza virus and CMV. After infection with influenza virus or CMV, IL-6 release into the medium increased (1756.5 ± 156.9 pg/mL vs 284.4 ± 55.3 pg/mL; P
- Published
- 1999
9. Preferential clearance of apoB-48-containing lipoproteins after heparin-induced lipolysis is modulated by lipoprotien lipase activity
- Author
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van Beek, AP, van Barlingen, HJJ, de Ruijter-Heijstek, FC, Jansen, H, Erkelens, DW, Dallinga-Thie, GM, de Bruin, TWA, and Biochemistry
- Published
- 1998
10. ELEVATED CHOLESTERYL ESTER TRANSFER PROTEIN-ACTIVITY IN IDDM MEN WHO SMOKE - POSSIBLE FACTOR FOR UNFAVORABLE LIPOPROTEIN PROFILE
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DULLAART, RPF, GROENER, JEM, DIKKESCHEI, BD, ERKELENS, DW, DOORENBOS, H, and Lifestyle Medicine (LM)
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PLASMA ,RABBIT ,LIPID TRANSFER ,INHIBITION ,nutritional and metabolic diseases ,lipids (amino acids, peptides, and proteins) ,CIGARETTE-SMOKING ,EXCHANGE ,DISEASE ,SERUM - Abstract
Objectives: To determine the effect of cigarette smoking on the activity of cholesteryl ester transfer protein (CETP) and high-density (HDL), low-density (LDL), and very-low-density (VLDL) lipoproteins in insulin-dependent diabetic (IDDM) men with microvascular complications. Research Design and Methods: We performed a case-control study in a referral-based diabetes clinic on a sequential sample of 9 cigarette-smoking and 12 nonsmoking IDDM men with microvascular complications and 12 nonsmoking control men. CETP activity was determined in each serum with an isotope assay with exogenous cholesteryl ester-labeled LDL and HDL. The method is independent of the endogenous lipoprotein present in serum. Results: The HDL-cholesterol (VLDL and LDL) ratio was lower in the smoking diabetic men than in the other groups (P
- Published
- 1991
11. THE ACTIVITY OF CHOLESTERYL ESTER TRANSFER PROTEIN IS DECREASED IN HYPOTHYROIDISM - A POSSIBLE CONTRIBUTION TO ALTERATIONS IN HIGH-DENSITY-LIPOPROTEINS
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DULLAART, RPF, HOOGENBERG, K, GROENER, JEM, DIKKESCHEI, LD, ERKELENS, DW, DOORENBOS, H, and Lifestyle Medicine (LM)
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TRANSFER EXCHANGE ACTIVITY ,endocrine system diseases ,SUBSTITUTION ,METABOLISM ,HEPATIC LIPASE ,CHOLESTEROL METABOLISM ,HYPOTHYROIDISM ,polycyclic compounds ,THYROXINE ,HIGH-DENSITY LIPOPROTEINS ,SERUM-LIPIDS ,lipids (amino acids, peptides, and proteins) ,TRIGLYCERIDE ,LIPID-TRANSFER PROTEIN ,THYROID-DYSFUNCTION ,HUMAN-PLASMA ,CHOLESTERYL ESTER TRANSFER ACTIVITY - Abstract
The activity of cholesteryl ester transfer protein is instrumental in the distribution of cholesteryl ester between lipoproteins in plasma. We measured the activity of cholesteryl ester transfer protein in plasma, designated cholesteryl ester transfer activity, as the rate of cholesteryl ester transfer between exogenous radiolabelled low-density and high-density lipoproteins. The effect of hypothyroidism on cholesteryl ester transfer activity was investigated in 13 athyreotic patients who were studied in the hypothyroid condition and in the euthyroid state, after they had received triiodothyronine supplementation for 33 to 67 days. During hypothyroidism plasma total cholesterol, very-low- plus low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, plasma triacylglycerol, apolipoprotein A1 and B were significantly higher than in the euthyroid state. Cholesteryl ester transfer activity was 15% lower during hypothyroidism (P
- Published
- 1990
12. Mortality in elderly patients with subclinical hyperthyroidism
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Twickler, Th B, primary, Cramer, MJM, additional, Koppeschaar, HPF, additional, de Vries, WR, additional, and Erkelens, DW, additional
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- 2002
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13. A comparison of the effects of simvastatin and pravastatin monotherapy on muscle histology and permeability in hypercholesterolaemic patients.
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Contermans, J, primary, Smit, JW, additional, Bar, PR, additional, and Erkelens, DW, additional
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- 1995
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14. Tulp syndrome
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Erkelens, DW, primary, de Bruin, TWA, additional, and Cabezas, MC, additional
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- 1993
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15. Different postprandial metabolism of olive oil and soybean oil: a possible mechanism of the high-density lipoprotein conserving effect of olive oil
- Author
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de Bruin, TW, primary, Brouwer, CB, additional, van Linde-Sibenius Trip, M, additional, Jansen, H, additional, and Erkelens, DW, additional
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- 1993
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16. Different clearance of intravenously administered olive oil and soybean-oil emulsions: role of hepatic lipase
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Brouwer, CB, primary, de Bruin, T W A, additional, Jansen, H, additional, and Erkelens, DW, additional
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- 1993
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17. Metformin and lactic acidosis: cause or coincidence? A review of case reports.
- Author
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Stades AME, Heikens JT, Erkelens DW, Holleman F, Hoekstra JBL, Stades, A M E, Heikens, J T, Erkelens, D W, Holleman, F, and Hoekstra, J B L
- Abstract
Objective: Metformin has been associated with the serious side-effect lactic acidosis. However, it remains unclear whether the use of metformin was a cause or a coincidence in lactic acidosis.Design: A literature search of the Index Medicus (1959-66) and of the databases Embase, Medline, Medline Express (1966-99) was performed using the keywords metformin, biguanides and lactic acidosis. All articles of cases with metformin-induced lactic acidosis (MILA) were cross-referenced.Subjects: Cases were included for analysis if they met the following criteria: serum pH < or =7.35, lactate concentration > or =5 mmol L(-1).Intervention: A forum of six experts in intensive care medicine independently categorized the cases in MILA unlikely (score 0), possible MILA (score 1) or probable MILA (score 2).Main Outcome Measures: Statistical analysis included the paired interobserver agreement (kappa) and multivariate regression analysis.Results: Of 80 reported cases, 33 were excluded because of insufficient quality. The forum scores of the remaining 47 cases were distributed normally with a mean score of 7 (range 2-10). The kappa-value was 0.041 (SD = 0.24, range -0.514, 0.427). Neither lactate concentration nor mortality correlated with serum metformin concentrations.Conclusions: Given the low interobserver agreement and the lack of any relationship between metformin levels and outcome parameters, the concept that there is a simple, causal relationship between metformin use and lactic acidosis in diabetic patients has to be reconsidered. [ABSTRACT FROM AUTHOR]- Published
- 2004
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18. Neurophysiological changes in the central and peripheral nervous system of streptozotocin-diabetic rats. Course of development and effects of insulin treatment.
- Author
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Biessels, GJ, Cristino, NA, Rutten, GJ, Hamers, FPT, Erkelens, DW, and Gispen, WH
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- 1999
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19. Injection site effects on the pharmacokinetics and glucodynamics of insulin lispro and regular insulin.
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ter Braak EW, Woodworth JR, Bianchi R, Cerimele B, Erkelens DW, Thijssen JHH, Kurtz D, ter Braak, E W, Woodworth, J R, Bianchi, R, Cerimele, B, Erkelens, D W, Thijssen, J H, and Kurtz, D
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- 1996
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20. Comparison of LysB28, ProB29-human insulin analog and regular human insulin in the correction of incidental hyperglycemia.
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Holleman F, van den Brand JJG, Hoven RAR, van der Linden JM, van der Tweel I, Hoekstra JBL, Erkelens DW, Holleman, F, van den Brand, J J, Hoven, R A, van der Linden, J M, van der Tweel, I, Hoekstra, J B, and Erkelens, D W
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- 1996
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21. EFFECT OF INDOMETHACIN IN 2 SIBLINGS WITH A RENIN-DEPENDENT HYPERTENSION, HYPER-ALDOSTERONISM AND HYPOKALEMIA
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DEJONG, PE, DONKER, AJM, VANDERWALL, E, ERKELENS, DW, VANDERHEM, GK, and DOORENBOS, H
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- 1980
22. LIMITATIONS OF VALUE OF LIPOPROTEIN ELECTROPHORESIS IN DIAGNOSIS AND TREATMENT OF HYPERLIPIDAEMIA
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ERKELENS, DW
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- 1974
23. CLINICAL-EXPERIENCE WITH SIMVASTATIN COMPARED WITH CHOLESTYRAMINE
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ERKELENS, DW, BAGGEN, MGA, VANDOORMAAL, JJ, KETTNER, M, KONINGSBERGER, JC, and MOL, MJTM
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- 1988
24. GLUCOSE-TOLERANCE AND INSULIN RELEASE, MATHEMATICAL APPROACH .1. ASSAY OF BETA-CELL RESPONSE AFTER ORAL GLUCOSE LOADING
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SLUITER, WJ, ERKELENS, DW, REITSMA, WD, and DOORENBOS, H
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- 1976
25. GLUCOSE-TOLERANCE AND INSULIN RELEASE, MATHEMATICAL APPROACH .2. APPROXIMATION OF PERIPHERAL INSULIN RESISTANCE AFTER ORAL GLUCOSE LOADING
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SLUITER, WJ, ERKELENS, DW, TERPSTRA, P, REITSMA, WD, and DOORENBOS, H
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- 1976
26. INCREASED CHOLESTERYLESTER TRANSFER ACTIVITY IN COMPLICATED TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS - ITS RELATIONSHIP WITH SERUM-LIPIDS
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DULLAART, RPF, GROENER, JEM, DIKKESCHEI, LD, ERKELENS, DW, DOORENBOS, H, and Lifestyle Medicine (LM)
- Published
- 1989
27. HMG COA REDUCTASE INHIBITION DECREASES LOW-DENSITY LIPOPROTEIN CHOLESTEROL (LDL-C) AND TRIGLYCERIDES (TG) IN FEMALE ANALBUMINEMIC RATS
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Joles, Ja, Willekeskoolschijn, N., Ton Rabelink, Erkelens, Dw, and Vontol, A.
28. EFFECTS OF SIMVASTATIN AND CHOLESTYRAMINE ON LIPOPROTEIN PROFILE IN HYPERLIPEMIA OF NEPHROTIC SYNDROME
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Ton Rabelink, Hene, Rj, Erkelens, Dw, Joles, Ja, and Koomans, Ha
29. Insulin resistance syndrome and type 2 diabetes mellitus.
- Author
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Erkelens DW and Erkelens, D W
- Abstract
Patients with type 2 diabetes mellitus have an elevated risk of morbidity and mortality from cardiovascular disease. This risk is partly attributable to an increased prevalence of classic coronary artery disease risk factors and partly because of hyperglycemia itself and a highly atherogenic lipid profile. The altered composition of lipoproteins and lipids in type 2 diabetic patients, termed diabetic dyslipidemia, is characterized by: (1) elevated levels of triglyceride; (2) normal levels of total and low-density lipoprotein cholesterol (LDL-C); (3) reduced levels of high-density lipoprotein cholesterol (HDL-C); (4) elevated levels of apolipoprotein B; (5) a preponderance of small, dense LDL particles; and (6) increased levels of cholesterol-rich very-low-density lipoprotein. In most cases, diabetic dyslipidemia is preceded by hyperinsulinemia resulting from insulin resistance. Because patients with type 2 diabetes and insulin resistance are at a markedly increased risk of atherosclerosis, and because strict control of glycemia has proved beneficial in reducing microangiopathy but not macroangiopathy, treatment of diabetic dyslipidemia should be aggressive. Target levels have, therefore, been set at <2.6 mmol/L (100 mg/dL) for LDL-C, <2.3 mmol/L [200 mg/dL] for triglycerides, and >1.15 mmol/L (45 mg/dL) for HDL-C. Trial data suggest that these target levels are likely to be achieved with statins, if necessary, in combination with fibrates or nicotinic acid derivatives. Furthermore, in large-scale clinical trials (eg, Scandinavian Simvastatin Survival Study [4S] and the Cholesterol and Recurrent Events [CARE] study), it has been demonstrated that lipid lowering can appreciably reduce cardiovascular events in diabetic patients. [ABSTRACT FROM AUTHOR]
- Published
- 2001
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30. A practical insulin infusion algorithm for the establishment of euglycaemia in both lean and obese patients with type 1 and type 2 diabetes.
- Author
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Stork AD, Erkelens DW, and Veneman TF
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- Adult, Age Factors, Aged, Body Mass Index, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 2 blood, Glycated Hemoglobin analysis, Humans, Infusion Pumps, Middle Aged, Algorithms, Blood Glucose drug effects, Diabetes Mellitus, Type 1 drug therapy, Diabetes Mellitus, Type 2 drug therapy, Insulin therapeutic use, Insulin Infusion Systems, Obesity blood, Thinness blood
- Abstract
Background: Both in research and in various clinical situations, prolonged euglycaemia can be desirable. In recent years, its benefit in (critically) ill patients and patients with acute myocardial infarction has been established. The objective of this study was to assess safety and efficacy of a practical, bodyweight-dependent algorithm to establish euglycaemia in both lean and obese patients with type 1 and type 2 diabetes., Methods: In 43 patients with type 1 diabetes and 17 patients with type 2 diabetes insulin were infused overnight to establish euglycaemia. Plasma glucose concentration was determined at 45 min intervals, and the insulin infusion rate was altered according to the algorithm., Results: Baseline plasma glucose concentrations were 13.1+/- 4.4 and 12.7 +/- 4.0 mmol/l in type 1 and type 2 diabetic patients, respectively. In both groups mean plasma glucose was reduced below 8.0 mmol/l within 3 h, and averaged 7.4 +/- 1.4 and 7.2 +/- 1.0 mmol/l (P = 0.11) over the next 7 h. Five (11.6%) patients with type 1 diabetes required administration of glucose because plasma glucose concentrations fell below 4.4 mmol/l. Consequently, type 1 diabetic patients were hypoglycaemic during 0.89% of the total study period. The lowest plasma glucose recorded was 3.9 mmol/l. In the type 2 diabetic patients the lowest plasma glucose was 5.5 mmol/l and no glucose administration was required for near-hypoglycaemia. The algorithm was equally effective in both lean and obese patients., Conclusions: Euglycaemia was established simply, swiftly and safely during the study period with the practical weight-based algorithm used in this study, in both lean and obese type 1 and type 2 diabetic patients, with a very low rate of mild hypoglycaemia. The algorithm is applicable in research and various several clinical settings. Its validity for a prolonged period of time and in critically ill patients needs to be further evaluated.
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- 2006
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31. Comparison of the accuracy of the HemoCue glucose analyzer with the Yellow Springs Instrument glucose oxidase analyzer, particularly in hypoglycemia.
- Author
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Stork AD, Kemperman H, Erkelens DW, and Veneman TF
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- Adult, Aged, Blood Glucose metabolism, Chemistry, Clinical standards, Female, Glucose Clamp Technique, Glucose Oxidase, Humans, Hyperinsulinism blood, Hyperinsulinism diagnosis, Male, Middle Aged, Regression Analysis, Reproducibility of Results, Blood Glucose analysis, Chemistry, Clinical instrumentation, Hypoglycemia blood, Hypoglycemia diagnosis
- Abstract
Objective: We aimed to assess the accuracy of the HemoCue Beta-glucose analyzer (HemoCue) and its correlation with the Yellow Springs Instrument (YSI 2300 STAT; YSI) glucose oxidase analyzer, in particular for hypoglycemic values., Design and Methods: Samples were taken from 24 volunteers during hyperinsulinemic glucose clamp studies. Glucose concentrations were determined immediately with the HemoCue in whole blood and with the YSI in plasma from the same sample. After correction for the difference between whole blood and plasma, the paired plasma glucose concentrations were analyzed with various statistical methods., Results: A total of 500 paired glucose values were obtained, 209 of which were in the hypoglycemic range. Mean+/-s.e. values were 4.85+/-0.004 mmol/l for the HemoCue (range 1.87-16.17) and 4.81+/-0.004 mmol/l for the YSI (range 1.88-15.00; P = 0.80). In the hypoglycemic region, values were 3.26+/-0.004 mmol/l for the HemoCue (range 1.87-5.17) and 3.22+/-0.003 mmol/l for the YSI (range 1.88-4.20; P = 0.59). Regression analyses were HemoCue = 1.019(YSI) -0.0577 mmol/l, with r = 0.9787 for all values; for hypoglycemic values the HemoCue = 1.1169(YSI) -0.3393 mmol/l, with r = 0.8798. Using Altman's residual plot, the difference was 0.03+/-0.0009 mmol/l, with 18 (3.6%) paired values outside the 95% limits of agreement (-0.82 to 0.89 mmol/l). In the hypoglycemic range, the difference was 0.04+/-0.001 mmol/l, with six (2.9%) values outside the 95% limits of agreement (-0.71 to 0.79 mmol/l). In error grid analysis, one value was in zone D (0.2%) and five values (1%) were in zone B; 98.8% were within zone A., Conclusions: Determination of glucose with the HemoCue system had very good correlation with the YSI system in a broad range of glycemia and also for hypoglycemic values. We believe that these methods can be used interchangeably for research and clinical purposes in adults.
- Published
- 2005
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32. Effects of atorvastatin on the clearance of triglyceride-rich lipoproteins in familial combined hyperlipidemia.
- Author
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Castro Cabezas M, Verseyden C, Meijssen S, Jansen H, and Erkelens DW
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- Administration, Oral, Adult, Apolipoproteins B blood, Atorvastatin, Cholesterol blood, Fat Emulsions, Intravenous pharmacology, Fats administration & dosage, Fats pharmacology, Female, Humans, Lipoproteins blood, Male, Middle Aged, Triglycerides blood, Triglycerides pharmacokinetics, Heptanoic Acids therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hyperlipidemia, Familial Combined blood, Hyperlipidemia, Familial Combined drug therapy, Lipoproteins antagonists & inhibitors, Pyrroles therapeutic use, Triglycerides antagonists & inhibitors
- Abstract
Familial combined hyperlipidemia (FCHL) patients have an impaired catabolism of postprandial triglyceride (TG)-rich lipoproteins (TRLs). We investigated whether atorvastatin corrects the delayed clearance of large TRLs in FCHL by evaluating the acute clearance of Intralipid (10%) and TRLs after oral fat-loading tests. Sixteen matched controls were included. Atorvastatin reduced fasting plasma TG (from 3.6 +/- 0.4 to 2.5 +/- 0.3 mM; mean +/- SEM) without major effects on fasting apolipoprotein B48 (apoB48) and apoB100 in large TRLs. Atorvastatin significantly reduced fasting intermediate density lipoprotein (Svedberg flotation, 12-20)-apoB100 concentrations. After Intralipid, TG in plasma and TRL showed similar kinetics in FCHL before and after atorvastatin treatment, although compared with controls, the clearance of large TRLs was only significantly slower in untreated FCHL, suggesting an improvement by atorvastatin. Investigated with oral fat-loading tests, the clearance of very low density lipoprotein (Sf20-60)-apoB100 improved by 24%, without major changes in the other fractions. The most striking effects of atorvastatin on postprandial lipemia in FCHL were on hepatic TRL, without major improvements on intestinal TRLs. Fasting plasma TG should be reduced more aggressively in FCHL to overcome the lipolytic disturbance causing delayed clearance of postprandial TRLs.
- Published
- 2004
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33. Acromegaly and heart failure: revisions of the growth hormone/insulin-like growth factor axis and its relation to the cardiovascular system.
- Author
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Twickler TB, Cramer MJ, Senden SP, Doevendans PA, de Vries WR, Erkelens DW, and Koppeschaar HP
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- Cardiomyopathy, Hypertrophic physiopathology, Growth Hormone blood, Heart Failure physiopathology, Hemodynamics, Humans, Myocytes, Cardiac physiology, Octreotide therapeutic use, Ventricular Function, Left physiology, Acromegaly physiopathology, Insulin-Like Growth Factor Binding Proteins physiology
- Abstract
Cardiomyopathy is a major cause of death in overt acromegaly. Recent progress in research has increasingly revealed the molecular mechanisms concerning growth hormone and insulin-like growth factor in the development of heart failure. In this article, we propose mechanisms according to which heart failure occurs, and we aim to extrapolate this knowledge to more general processes involved in heart failure.
- Published
- 2004
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34. Sex steroids and plasma lipoprotein levels in healthy women: The importance of androgens in the estrogen-deficient state.
- Author
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Van Beek AP, de Ruijter-Heijstek FC, Jansen H, Erkelens DW, and de Bruin TW
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- Fasting metabolism, Female, Humans, Kinetics, Lipoproteins, VLDL blood, Middle Aged, Postmenopause physiology, Premenopause physiology, Regression Analysis, Androgens physiology, Estrogens deficiency, Gonadal Steroid Hormones blood, Lipoproteins blood
- Abstract
The role of endogenous estrogens and androgens and their potential interaction in atherosclerosis is not well understood. Therefore, we investigated the effects of natural menopause and endogenous sex steroids on triglycerides (TG), a major risk factor for cardiovascular disease in women. Fasting lipid and lipoprotein concentrations, postheparin lipase activities, kinetic indicators of triglyceride lipolysis, and various hormone levels, including dehydroepiandrostenedione-sulfate (DHEA-S), (bioavailable) testosterone, and androstenedione, were determined in 18 premenopausal and 18 postmenopausal women, matched for age and body composition. Fasting plasma TG were 0.69 +/- 0.29 mmol/L in postmenopausal women and 0.73 +/- 0.33 mmol/L in premenopausal women (difference not significant [NS]). Approximately 30% of all plasma TG were present in the very-low-density lipoproteins (VLDLs) in both groups. No differences were found between groups in plasma lipolytic potential of TG-rich lipoproteins. Univariate analysis revealed that VLDL-TG concentrations were strongly related to insulin (r = 0.84, P =.0001) and androstenedione (r = 0.65, P =.004) in postmenopausal women. Multivariate analysis of potential determinants of VLDL-TG showed that insulin, androstenedione, and bioavailable testosterone were independent variables, explaining 87% of the variability (r = 0.93, P =.0001) in postmenopausal women. In contrast, in premenopausal women, the only identified predictor of fasting VLDL-TG in univariate and multivariate analysis was insulin (r = 0.72, P =.001). Our results show that the association of androgens with TG varied depending on androgen concentrations, the relative androgenic potential, and most importantly on hormonal milieu. Endogenous androgens were only related to plasma VLDL-TG in the estrogen-deficient state.
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- 2004
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35. Normalization of daytime triglyceridemia by simvastatin in fasting normotriglyceridemic patients with premature coronary sclerosis.
- Author
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van Wijk JP, Halkes CJ, De Jaegere PP, Plokker HW, Erkelens DW, and Cabezas MC
- Subjects
- Adult, Aged, Apolipoprotein A-I blood, Apolipoprotein A-I drug effects, Apolipoproteins B blood, Apolipoproteins B drug effects, Area Under Curve, Biomarkers blood, Blood Pressure drug effects, Body Mass Index, Coronary Artery Disease epidemiology, Dietary Fats administration & dosage, Dose-Response Relationship, Drug, Energy Intake drug effects, Female, Humans, Hypertriglyceridemia epidemiology, Hypolipidemic Agents administration & dosage, Male, Metabolic Syndrome blood, Metabolic Syndrome drug therapy, Metabolic Syndrome epidemiology, Middle Aged, Netherlands, Predictive Value of Tests, Risk Factors, Sex Factors, Simvastatin administration & dosage, Treatment Outcome, Circadian Rhythm physiology, Coronary Artery Disease blood, Coronary Artery Disease drug therapy, Fasting blood, Hypertriglyceridemia blood, Hypertriglyceridemia drug therapy, Hypolipidemic Agents therapeutic use, Simvastatin therapeutic use, Triglycerides blood
- Abstract
Postprandial hyperlipidemia is associated with premature coronary sclerosis in fasting normolipidemic subjects. Self-determined daytime capillary triglyceride (cTG) profiles were compared between 26 fasting normotriglyceridemic patients with premature coronary artery disease (CAD) and 26 controls matched for gender, age and BMI. Daytime triglyceridemia was calculated as total area under the cTG-curve (cTG-AUC). Total and LDL cholesterol were not different between CAD patients (5.4+/-0.8 mmol/l and 3.6+/-0.7 mmol/l, respectively) and controls (5.0+/-0.9 mmol/l and 3.3+/-0.8 mmol/l, respectively). Patients with CAD were characterized by a 44% higher cTG-AUC than matched controls (P<0.01). Using logistic regression analysis, cTG-AUC was the strongest predictor of the presence of CAD (P<0.001). Adding apo AI to the model improved the predictive power from 71 to 77%. Sixteen patients were studied after increasing doses of simvastatin up to 80 mg/day. Although the target for LDL cholesterol was reached by simvastatin 20mg/day, significant effects on cTG-AUC were found only by higher doses of simvastatin. Simvastatin 40 mg/day decreased cTG-AUC by 28% (P<0.05 versus baseline), reaching comparable values as in controls, without further improvement with simvastatin 80 mg/day (26% reduction versus baseline; P<0.05). Daytime triglyceridemia is linked to premature coronary sclerosis in fasting normotriglyceridemic patients. A higher dose of simvastatin was needed to normalize daytime triglyceridemia than was required to "normalize" LDL cholesterol.
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- 2003
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36. Gender differences in postprandial ketone bodies in normolipidemic subjects and in untreated patients with familial combined hyperlipidemia.
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Halkes CJ, van Dijk H, Verseyden C, de Jaegere PP, Plokker HW, Meijssen S, Erkelens DW, and Cabezas MC
- Subjects
- 3-Hydroxybutyric Acid blood, Adult, Area Under Curve, Complement C3 metabolism, Dietary Fats administration & dosage, Dietary Fats metabolism, Fatty Acids, Nonesterified blood, Female, Humans, Hyperlipidemia, Familial Combined blood, Male, Middle Aged, Postprandial Period, Sex Characteristics, Triglycerides blood, Fatty Acids, Nonesterified metabolism, Hyperlipidemia, Familial Combined metabolism, Ketone Bodies metabolism
- Abstract
Objective: An increased hepatic flow of free fatty acids (FFAs) is associated with impaired peripheral FFA trapping by malfunctioning of the complement component 3 (C3)/acylation-stimulating protein system and overproduction of VLDL in familial combined hyperlipidemia (FCHL). Postprandial ketone bodies reflect FFA oxidation in the liver, but the postprandial changes in male and female patients separately have not been determined yet. Gender differences in postprandial ketone bodies and C3 changes were investigated in normolipidemic patients and patients with untreated FCHL., Methods and Results: Thirty-two normolipidemic patients (16 female and 16 male) and 19 patients with untreated normolipidemia (9 female and 10 male) underwent an oral fat-loading test. Total and incremental areas under the curves (AUC and dAUC, respectively) after the oral fat load were calculated. Triglyceride AUC was similar between genders in each group. Normolipidemic female subjects showed a higher levels of dAUC-hydroxybutyric acid than male subjects (1.37+/-0.49 and 0.98+/-0.43 mmol x h/L). In FCHL, a similar trend was observed in female (1.92+/-0.38) compared with male (1.55+/-0.87) subjects. In contrast to normolipidemia, FCHL did not show a postprandial increase in C3, although C3 was higher in FCHL., Conclusions: Women have higher postprandial ketone bodies than men, probably reflecting enhanced postprandial hepatic FFA oxidation. In FCHL, both genders have higher postprandial ketone bodies and therefore higher hepatic FFA delivery. The higher fasting and postprandial C3 levels in FCHL may reflect resistance of the C3/acylation-stimulating protein system to promote peripheral fatty acid trapping.
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- 2003
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37. [The growth hormone/insulin-like growth factor axis. What is its role in the atherosclerotic process?].
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Twickler TB, Bruckert E, Cramer MJ, Erkelens DW, and Koppeschaar HP
- Subjects
- Age of Onset, Humans, Risk Factors, Arteriosclerosis physiopathology, Human Growth Hormone deficiency, Human Growth Hormone pharmacology, Somatomedins pharmacology
- Abstract
Unlabelled: GROWTH HORMONE AND ATHEROSCLEROSIS: Adult-onset growth hormone (GH) deficiency is associated with an increase in cardiovascular morbidity and mortality., Mechanisms: Other than classical risk factors, such as dyslipidemia, a direct interaction between the activity of the GH/IGF-1 axis and the endothelium also plays a part. It is possible that the modulating effect of IGF-1 on nitric oxide (NO) synthesis is also important, together with the anabolic effect on the myocardiocytes. Substitution of recombinant GH induces rapid reduction in the atherosclerotic plaques, suggesting a direct effect of the GH/IGF axis on the atherosclerotic process. In addition to the acquired GH deficiency, as in non-substituted patients following hypophysectomy, attention has recently been focused on the relative GH deficiency as is seen in obesity and in the course of ageing. PERSPECTIVES FOR CARDIOVASCULAR ENDOCRINOLOGY: Therapeutic intervention in the GH/IGF axis might influence the atherosclerotic process. Study of the GH/IGF axis activity and of its correlation with atherosclerosis opens new perspectives in the understanding of the role of this axis in cardiovascular diseases.
- Published
- 2003
38. Fasting and daylong triglycerides in obesity with and without type 2 diabetes.
- Author
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van Wijk JP, Halkes CJ, Erkelens DW, and Castro Cabezas M
- Subjects
- Adult, Aged, Anthropometry, Area Under Curve, Circadian Rhythm physiology, Diet, Female, Humans, Male, Middle Aged, Point-of-Care Systems, Reference Values, Diabetes Mellitus, Type 2 blood, Fasting metabolism, Obesity blood, Triglycerides blood
- Abstract
Postprandial hypertriglyceridemia associated with insulin resistance is one of the cardiovascular risk factors in obesity and type 2 diabetes. It is not known whether diabetics have a more pronounced postprandial hypertriglyceridemia than obese subjects. Daylong triglyceridemia, representing postprandial lipemia, was determined in obese subjects with and without type 2 diabetes and in lean subjects. Nineteen type 2 diabetics (F/M: 7/12, body mass index [BMI]: 30.6 +/- 5.4 kg/m(2)), 45 obese nondiabetics (F/M: 16/29, BMI: 29.5 +/- 2.6 kg/m(2)) and 78 lean subjects (F/M: 28/50, BMI: 23.7 +/- 2.2 kg/m(2)) measured capillary triglycerides (TGc) during 3 days on 6 fixed time-points each day in an out-of-hospital situation. Daylong TGc profiles were calculated as mean integrated area under the TGc-curve (TGc-AUC). Fasting plasma TG were higher in diabetics and obese nondiabetics (1.81 +/- 0.79 and 1.77 +/- 0.80 mmol/L) compared with lean subjects (1.23 +/- 0.67 mmol/L, P <.001). TGc-AUC was similarly increased in both diabetics and obese nondiabetics (35.0 +/- 12.1 and 35.2 +/- 10.6 mmol.1 h/L) compared with lean controls (25.5 +/- 12.0 mmol.1 h/L, P <.001). Self-reported energy intake was not significantly different between the groups. Fasting TGc (r =.87, P <.001) and waist circumference (r =.51, P <.001) were the parameters best associated with TGc-AUC. Using stepwise multiple regression analysis, fasting TGc, BMI, total cholesterol, and high-density lipoprotein (HDL) cholesterol were the best predictors of TGc-AUC, explaining 77% of the variation. The cut-off level for "normal" TGc-AUC, calculated as the 75th percentile of TGc-AUC in lean subjects, was 30.7 mmol.1 h/L and corresponded with a fasting TGc of 1.8 mmol/L (eg, 1.6 mmol/L in plasma), calculated using univariate regression analysis. In conclusion, daylong triglyceridemia is similarly increased in diabetics and obese nondiabetics compared with lean subjects. Fasting TG and central obesity largely determine daylong triglyceridemia, independent of the presence of type 2 diabetes. Decreasing fasting plasma TG below 1.6 mmol/L could lead to a normalization of postprandial lipemia in obese subjects with and without diabetes.
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- 2003
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39. Adult-onset growth hormone deficiency: Relation of postprandial dyslipidemia to premature atherosclerosis.
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Twickler TB, Cramer MJ, Dallinga-Thie GM, Chapman MJ, Erkelens DW, and Koppeschaar HP
- Subjects
- Age of Onset, Humans, Hyperlipidemias genetics, Phenotype, Postprandial Period, Arteriosclerosis etiology, Human Growth Hormone deficiency, Hyperlipidemias complications
- Published
- 2003
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40. Common cholesteryl ester transfer protein gene polymorphisms and the effect of atorvastatin therapy in type 2 diabetes.
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van Venrooij FV, Stolk RP, Banga JD, Sijmonsma TP, van Tol A, Erkelens DW, and Dallinga-Thie GM
- Subjects
- Aged, Atorvastatin, Base Sequence, Cholesterol blood, Cholesterol Ester Transfer Proteins, Cholesterol Esters metabolism, DNA Primers, Diabetes Mellitus, Type 2 blood, Double-Blind Method, Female, Genotype, Glycated Hemoglobin metabolism, Humans, Male, Middle Aged, Patient Selection, Placebos, Restriction Mapping, Triglycerides blood, Carrier Proteins genetics, Diabetes Mellitus, Type 2 drug therapy, Glycoproteins, Heptanoic Acids therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Polymorphism, Genetic, Pyrroles therapeutic use
- Abstract
Objective: The cholesteryl ester transfer protein (CETP) plays a key role in the remodeling of triglyceride (TG)-rich and HDL particles. Sequence variations in the CETP gene may interfere with the effect of lipid-lowering treatment in type 2 diabetes., Research Design and Methods: We performed a 30-week randomized double-blind placebo-controlled trial with atorvastatin 10 mg (A10) and 80 mg (A80) in 217 unrelated patients with diabetes., Results: CETP TaqIB and A-629C polymorphisms were tightly concordant (P < 0.001). At baseline, B1B1 carriers had lower plasma HDL cholesterol (0.99 +/- 0.2 vs. 1.11 +/- 0.2 mmol/l, P < 0.05), higher CETP mass (2.62 +/- 0.8 vs. 2.05 +/- 0.4 mg/l, P < 0.001), and slightly increased, though not significant, plasma TGs (2.7 +/- 1.05 vs. 2.47 +/- 0.86, P = 0.34) compared with B2B2 carriers. Atorvastatin treatment significantly reduced CETP mass dose-dependently by 18% (A10) and 29% (A80; both vs. placebo P < 0.001, A10-A80 P < 0.001). CETP mass and activity were strongly correlated (r = 0.854, P < 0.0001). CETP TaqIB polymorphism appeared to modify the effect of atorvastatin on HDL cholesterol elevation (B1B1 7.2%, B1B2 6.1%, B2B2 0.5%; P < 0.05), TG reduction (B1B1 39.7%, B1B2 38.4%, B2B2 18.4%; P = 0.08), and CETP mass reduction (B1B1 32.1%, B1B2 29.6%, B2B2 21.9%; P = 0.27, NS). Similar results were obtained for the A-629C polymorphism., Conclusions: In conclusion, the B1B1/CC carriers of the CETP polymorphisms have a more atherogenic lipid profile, including low HDL, and they respond better to statin therapy. These results favor the hypothesis that CETP polymorphisms modify the effect of statin treatment and may help to identify patients who will benefit most from statin therapy.
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- 2003
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41. Six-month efficacy of benfluorex vs. placebo or metformin in diet-failed type 2 diabetic patients.
- Author
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Del Prato S, Erkelens DW, and Leutenegger M
- Subjects
- Appetite Depressants adverse effects, Blood Glucose analysis, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 diet therapy, Double-Blind Method, Fasting blood, Female, Fenfluramine adverse effects, Glycated Hemoglobin antagonists & inhibitors, Humans, Hypoglycemic Agents adverse effects, Male, Metformin adverse effects, Middle Aged, Placebos adverse effects, Placebos therapeutic use, Retreatment, Treatment Failure, Treatment Outcome, Appetite Depressants therapeutic use, Diabetes Mellitus, Type 2 drug therapy, Fenfluramine analogs & derivatives, Fenfluramine therapeutic use, Hypoglycemic Agents therapeutic use, Metformin therapeutic use
- Abstract
Six-month efficacy of benfluorex (Mediator) (150-450 mg/day) was assessed in a double-blind multicenter study vs. placebo or metformin hydrochloride (850-2550 mg/day). After a 2-month run-in period of strict dieting, 722 type 2 diabetic patients were randomized (1:2:2) to receive placebo (n=144), benfluorex (n=294) or metformin (n=284). After a 5-week dose-finding phase, the efficacy of benfluorex was compared with that of placebo (test for difference, main analysis) and metformin (non-inferiority test, secondary analysis) during a 6-month fixed-dose treatment. At entry after strict dieting, there was no difference between groups for HbA(1C) (placebo, 7.4%+/-1.5%; benfluorex, 7.7%+/-1.6%; metformin, 7.8%+/-1.6%) and fasting plasma glucose (FPG; placebo, 9.7+/-2.3 mmol/l; benfluorex, 10.0+/-2.0 mmol/l; metformin, 10.2+/-2.5 mmol/l). At the end of the dose-finding phase, mean doses were 2.71 tablets/day for placebo group, 2.65 tablets/day for benfluorex (397.5 mg/day) and 2.50 tablets/day for metformin (2125 mg/day). At the end of treatment, HbA(1C) level decreased by 0.60% ( p<0.001) in benfluorex patients while it increased by 0.50% ( p<0.001) with placebo (intent-to-treat analysis). The mean endpoint difference was -0.86% (SE, 0.17%; p<0.001). Mean endpoint difference in HbA(1C) between benfluorex and metformin was 0.28% (SE, 0.12%) [90% CI, 0.07 to 0.48] (non-inferiority test, p=0.037). Treatment with benfluorex was well tolerated; 39% of these patients reported one or more emergent adverse events (compared to 38% on placebo and 43% on metformin) and only two patients suffered a treatment-related, serious adverse event. This study demonstrates that benfluorex: (1) significantly reduces HbA1C and fasting plasma glucose when compared to placebo; (2) has a good safety profile; and (3) has relatively lower potency compared to metformin, although the non-inferiority test (equivalence limit for HbA(1C) of 0.5%) was significant.
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- 2003
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42. Induction of postprandial inflammatory response in adult onset growth hormone deficiency is related to plasma remnant-like particle-cholesterol concentration.
- Author
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Twickler TB, Dallinga-Thie GM, Visseren FL, de Vries WR, Erkelens DW, and Koppeschaar HP
- Subjects
- Adult, Aged, Case-Control Studies, Cytokines blood, Female, Humans, Male, Middle Aged, Cholesterol blood, Human Growth Hormone deficiency, Inflammation etiology, Lipoproteins blood, Postprandial Period immunology, Triglycerides blood
- Abstract
Increased cardiovascular mortality due to premature atherosclerosis is a clinical feature in the adult-onset GH deficiency (AGHD) syndrome. Inflammation is a key feature in atherogenesis and may be triggered by postprandial lipoprotein remnants. We hypothesized that increased postprandial lipoprotein remnant levels in AGHD may be associated with an inflammatory response. In this case-control study, 10 AGHD patients [6 males and 4 females; age, 48 +/- 9 yr; body mass index (BMI), 26.9 +/- 2.6 kg/m(2)] and 10 healthy control subjects (matched for age, BMI, gender, baseline lipid levels, and apolipoprotein E genotype) were included. They all ingested an oral fat load. Fasting and postprandial levels of plasma remnant-like particle-cholesterol (RLP-C; 0.31 +/- 0.13 mmol/liter and 4.14 +/- 1.37 mmol/liter.h in GHD; 0.18 +/- 0.06 mmol/liter and 2.56 +/- 1.02 mmol/liter.h in controls, respectively) were significantly increased in AGHD patients compared with control subjects. The median inflammatory cytokines, IL-6 and TNF-alpha, were higher in the fasting [3.9 (range, 3.1-11.9) pg/ml and 6.8 (range, 2.5-27.6) pg/ml, respectively] and postprandial [151.7 (range, 87.0-294.3) pg/ml.24 h and 289.9 (range, 87.5-617.6) pg/ml.24 h, respectively] states in AGHD than in controls [fasting, 0.9 (range, 0.2-5.2) pg/ml and 2.8 (range, 2.5-5.7) pg/ml; and postprandial, 54.5 (range, 11.50-126.5) pg/ml.24 h and 118.3 (range, 81.2-243.1) pg/ml.24 h, respectively]. In addition, postprandial profile of RLP-C and IL-6 in AGHD and in the total group were significantly associated (r(2) = 0.44, P < 0.05; and r(2) = 0.38, P < 0.01, respectively). In conclusion, the increased postprandial RLP-C level in GHD is associated with an inflammatory response that may result in increased susceptibility for premature atherosclerosis.
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- 2003
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43. Differential effect of female gender on coronary artery disease and peripheral artery disease.
- Author
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van Lennep HW, Westerveld HT, Zwinderman AH, van Lennep JE, Slot HB, Erkelens DW, and van der Wall EE
- Abstract
Background: Women are relatively protected against coronary artery disease (CAD). Whether female gender has a similar protective influence on the development of peripheral artery disease (PAD) has not been extensively investigated and was the main subject of our study., Methods: We analysed 2707 consecutive patients (2008 men and 699 women) who underwent a first diagnostic coronary angiography for suspicion of CAD and 2367 consecutive patients (1426 men and 941 women) who underwent a first ankle arm index measurement because of suspicion of PAD., Results: We found that a positive diagnosis for CAD and PAD was more common in men compared with women (80.7% vs 57.9%, p<0.0001 and 68.0% vs 60.7%, p<0.0001). Once CAD or PAD was established, severity of disease was similar for men and women, which pleads against a referral bias. Women had a reduced risk of CAD after adjustment for risk factors (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.22-0.46, p<0.0001), but not of PAD (OR 0.82, 95% CI 0.66-1.03, p=NS). In patients with CAD and in those with PAD, women were older, more often had diabetes and hypertension, while men were more likely to be current smokers. Hypertension, smoking and diabetes were associated with CAD in both men and women. Current smoking was associated with PAD in men and women. Hypertension and diabetes were associated with PAD in women but not in men., Conclusion: After adjustment for risk factors, the female protection for CAD seems to less present for PAD.
- Published
- 2002
44. Modern aspects of atherosclerosis and treatment of lipid disorders.
- Author
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Erkelens DW and Schwandt P
- Subjects
- Coronary Artery Disease etiology, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Hyperlipidemias complications, Risk Factors, Stroke etiology, Stroke prevention & control, Coronary Artery Disease epidemiology, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hyperlipidemias drug therapy
- Published
- 2002
- Full Text
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45. Delayed and exaggerated postprandial complement component 3 response in familial combined hyperlipidemia.
- Author
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Meijssen S, van Dijk H, Verseyden C, Erkelens DW, and Cabezas MC
- Subjects
- Adult, Blood Proteins metabolism, Cerebrovascular Disorders blood, Chylomicrons blood, Dietary Fats metabolism, Fasting blood, Fasting metabolism, Fatty Acids, Nonesterified blood, Female, Humans, Hydroxybutyrates blood, Hyperlipidemias blood, Male, Myocardial Infarction blood, Triglycerides blood, Complement C3 metabolism, Complement C3a analogs & derivatives, Hyperlipidemia, Familial Combined blood, Postprandial Period physiology
- Abstract
Very low density lipoprotein overproduction is the major metabolic characteristic in familial combined hyperlipidemia (FCHL). Peripheral handling of free fatty acids (FFAs) in vitro may be impaired in FCHL by decreased action of acylation-stimulating protein (ASP), which is identical to the immunologically inactive complement component 3a (C3adesArg). Because decreased FFA uptake by impaired complement component 3 (C3) response (as the precursor for ASP) may result in enhanced FFA flux to the liver in FCHL, we have evaluated postprandial C3 changes in vivo in FCHL patients. Accordingly, 10 untreated FCHL patients and 10 matched control subjects underwent an oral fat loading test. Fasting plasma C3 and ASP levels were higher in FCHL patients (1.33+/-0.09 g/L and 70.53+/-4.37 mmol/L, respectively) than in control subjects (0.91+/-0.03 g/L and 43.21+/-8.96 mmol/L, respectively; P=0.01 and P<0.05). In control subjects, C3 concentrations increased significantly after 4 hours (to 1.03+/-0.04 g/L). In FCHL, plasma C3 was unchanged after 4 hours. The earliest postprandial C3 rise in FCHL patients occurred after 8 hours (1.64+/-0.12 g/L). The maximal apolipoprotein B-48 concentration was reached after 6 hours in FCHL patients and control subjects. Postprandial FFA and hydroxybutyric acid (as a marker of hepatic FFA oxidation) were significantly higher in FCHL patients than in control subjects, and the early postprandial C3 rise was negatively correlated with the postprandial FFA and hydroxybutyric acid concentrations. The present data suggest an impaired postprandial plasma C3 response in FCHL patients, most likely as a result of a delayed response by C3, as the precursor for the biologically active ASP, acting on FFA metabolism. Therefore, an impaired postprandial C3 response may be associated with impaired peripheral postprandial FFA uptake and, consequently, lead to increased hepatic FFA flux and very low density lipoprotein overproduction.
- Published
- 2002
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46. In vivo modulation of plasma free fatty acids in patients with familial combined hyperlipidemia using lipid-lowering medication.
- Author
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Meijssen S, Derksen RJ, Bilecen S, Erkelens DW, and Cabezas MC
- Subjects
- Adult, Catecholamines physiology, Female, Humans, Hyperlipidemia, Familial Combined physiopathology, Hyperlipidemia, Familial Combined psychology, Insulin blood, Insulin physiology, Male, Middle Aged, Reference Values, Sterol Esterase antagonists & inhibitors, Stress, Psychological complications, Sympathetic Nervous System physiopathology, Fatty Acids, Nonesterified blood, Hyperlipidemia, Familial Combined blood, Hyperlipidemia, Familial Combined drug therapy, Hypolipidemic Agents therapeutic use
- Abstract
One of the best studied aspects of the insulin resistance syndrome in familial combined hyperlipidemia (FCHL) is impaired insulin-mediated suppression of FFA by diminished inhibition of hormone-sensitive lipase (HSL). In vitro experiments have shown that stimulation of HSL activity by catecholamines is decreased in FCHL. The aim of this study was to investigate HSL inhibition by insulin and stimulation by endogenous catecholamines in vivo in FCHL patients. Twelve FCHL subjects using lipid-lowering medication and 12 controls underwent a mental stress test after random ingestion of either 50 g glucose or placebo. After ingestion of glucose, insulin concentrations increased from 76.8 +/- 21.5 pM to a maximum of 520.2 +/- 118.4 pM (P < 0.01) in FCHL and from 38.0 +/- 5.0 to 221.7 +/- 25.1 pM (P < 0.01) in controls. The percent decreases in plasma FFA during the first hour after glucose ingestion were similar in FCHL and controls (67 +/- 5% vs. 72 +/- 3%, respectively), suggesting a comparable inhibition of HSL in both. During the placebo test, FFA increased similarly in FCHL (56 +/- 9%) and controls (57 +/- 19%). In contrast, FFA concentrations did not change during mental stress after ingestion of glucose (from 0.17 +/- 0.02 to 0.15 +/- 0.02 mmol/liter in FCHL and from 0.11 +/- 0.02 to 0.12 +/- 0.02 mmol/liter in controls). In conclusion, the present study provides in vivo evidence for intact insulin-mediated suppression of FFA in FCHL, although this inhibition of HSL was achieved by higher insulin levels, suggesting insulin resistance at the level of HSL. Secondly, the induction of HSL activity by endogenous catecholamines in vivo is not decreased in FCHL, in contrast to earlier in vitro findings. Finally, catecholamine-induced HSL activation can be inhibited by insulin in a similar manner in both FCHL and controls.
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- 2002
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47. Additional lunchtime basal insulin during insulin lispro intensive therapy in a randomized, multicenter, crossover study in adults : a real-life design.
- Author
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Stades AM, Hoekstra JB, van den Tweel I, Erkelens DW, and Holleman F
- Subjects
- Adult, Body Mass Index, Cross-Over Studies, Diabetes Mellitus, Type 1 blood, Drug Administration Schedule, Eating, Female, Glycated Hemoglobin metabolism, Humans, Hypoglycemic Agents administration & dosage, Insulin administration & dosage, Insulin Lispro, Male, Blood Glucose metabolism, Diabetes Mellitus, Type 1 drug therapy, Hypoglycemia epidemiology, Hypoglycemic Agents therapeutic use, Insulin analogs & derivatives, Insulin therapeutic use, Insulin, Isophane therapeutic use
- Abstract
Objective: This study was performed to evaluate whether an additional dose of NPH insulin at lunchtime might overcome the deleterious effects of waning basal insulinemia on pre-dinner and evening glucose values during insulin lispro intensive therapy with once daily basal insulin at night., Research Design and Methods: The study was a 10-month multicenter, randomized, crossover trial. After a 2-month run-in period, subjects injected NPH insulin once (1 x NPH) or twice (2 x NPH) daily for 4 months in a randomized order. Adult patients were included if they had HbA(1c) levels <8.5%. Efficacy measures were HbA(1c) levels, 8-point glucose profiles, and the frequency of hypoglycemia. The statistical analysis included a within-patient comparison for crossover trials., Results: In all, 104 patients completed the trial. The mean HbA(1c) level before randomization was 7.1 +/- 0.85%. The HbA(1c) levels did not change significantly within patients (t test, mean difference = 0.06%; 95% confidence interval [CI] -0.073 to 0.20). The pre-dinner blood glucose values were significantly lower during the 2 x NPH daily protocol, with a mean difference of 0.76 mmol/l (t test, P = 0.004; CI 0.25 to 1.3). In the evening, the frequency of hypoglycemia increased significantly during the 2 x NPH daily protocol with a median difference of 0.56 mild episodes/30 days (P = 0.001) and 6.9 severe episodes/patient year (P = 0.007), respectively., Conclusions: Equal HbA(1c) levels and increasing frequencies of hypoglycemia in the evening overshadow the slight improvement of the evening glucose profiles during a regimen with 2 x NPH daily insulin. Therefore, generalized use of a second injection of NPH insulin at lunchtime cannot be recommended to all adult patients with type 1 diabetes using intensive insulin lispro therapy.
- Published
- 2002
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48. The continuous postprandial state of man and its influence on atherosclerosis.
- Author
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Twickler TB, Cramer MJ, Dallinga-Thie GM, and Erkelens DW
- Published
- 2002
49. Primary and secondary prevention in cardiovascular disease: an old-fashioned concept?
- Author
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van Venrooij FV, Stolk RP, Banga JD, Erkelens DW, and Grobbee DE
- Subjects
- Adult, Aged, Aging, Cardiovascular Diseases etiology, Child, Humans, Obesity complications, Risk Factors, Smoking adverse effects, Cardiovascular Diseases prevention & control, Primary Prevention methods
- Abstract
Objective: Is the concept of primary and secondary cardiovascular prevention an old-fashioned concept that needs to be re-defined?, Design: Discussion paper., Results: Cardiovascular prevention means reduction of absolute risk for cardiovascular disease (CVD), irrespective of clinical stage., Conclusion: For the calculation of an individual probability to develop CVD all factors that contribute to the risk must be taken into account, including previous CVD events.
- Published
- 2002
- Full Text
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50. Risk factors for coronary heart disease: implications of gender.
- Author
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Roeters van Lennep JE, Westerveld HT, Erkelens DW, and van der Wall EE
- Subjects
- Aged, Bacterial Infections complications, Biomarkers blood, C-Reactive Protein metabolism, Coronary Disease genetics, Diabetes Complications, Estrogens metabolism, Female, Fibrinogen metabolism, Homocysteine metabolism, Humans, Hypertension complications, Inflammation, Lipid Metabolism, Male, Middle Aged, Obesity complications, Psychosocial Deprivation, Risk Factors, Smoking adverse effects, Triglycerides metabolism, Coronary Disease etiology, Sex
- Abstract
It has been recognized over the past years that women form a distinct subpopulation within patients with coronary heart disease. This phenomenon should be acknowledged in the management and in the assessment of coronary heart disease. Over the past years remarkable progress has been made concerning our knowledge of cardiovascular risk factors related to gender. For instance, diabetes, high density lipoproteins and triglycerides levels have been found to have a greater impact on coronary heart disease risk in women compared to men. On the other hand, evidence showing that lipoprotein (a) is a cardiovascular risk factor seems to be stronger in men than in women. For optimal treatment and prevention of coronary heart disease it is necessary to acknowledge that it is not self-evident that women and men show similar responses to risk factors or to treatment. This review article addresses the role of cardiovascular risk factors focusing on the differential impact they might have on men and women.
- Published
- 2002
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