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5. Individualised versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome (IDEAL DVT): a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial

Author

ten Cate-Hoek, Arina J, ten Cate, Hugo, Joore, Manuela A, Prins, Martin H, Amin, Elham E, Bouman, Annemieke C, Meijer, Karina, Piersma-Wichers, Margriet, Tick, Lidwine W, Nijziel, Martin R, Middeldorp, Saskia, Lauw, Mandy, Cheung, Y Whitney, Mostard, Guy J M, ten Wolde, Marije, Bistervels, Ingrid M, van den Heiligenberg, Simone M, van Wissen, Sanne, van de Poel, Marlène H W, Otten, Hans-Martin, Serné, Erik H, Klappe, Edith H, Prandoni, Paolo, Vedovetto, Valentina, Villalta, Sabina, van de Poel, Marlène HW, and Lauw, Mandy N

Published
2018
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11. National diabetes registries: do they make a difference?:do they make a difference?

Author

Bak, Jessica C. G., Serne, Erik H., Kramer, Mark H. H., Nieuwdorp, Max, and Verheugt, Carianne L.

Abstract

Aims: The global epidemic of diabetes mellitus continues to expand, including its large impact on national health care. Measuring diabetes outcomes and their causes of variation highlights areas for improvement in care and efficiency gains; large registries carry this potential. By means of a systematic review, we aimed to give an overview of national registries worldwide by quantifying their data and assessing their influence on diabetes care. Methods: The literature on MEDLINE up to March 31, 2020, was searched, using keywords diabetes mellitus, national, registry, registration, and/or database. National disease-specific registries from corresponding articles were included. Database characteristics and clinical variables were obtained. All registries were compared to the ICHOM standard set of outcomes. Results: We identified 12 national clinical diabetes registries, comprising a total of 7,181,356 diabetic patients worldwide. Nearly all registries recorded weight, HbA1c, lipid profile, and insulin treatment; the recording of other variables varied to a great extent. Overall, registries corresponded fairly well with the ICHOM set. Most registries proved to monitor and improve the quality of diabetes care using guidelines as a benchmark. The effects on national healthcare policy were more variable and often less clear. Conclusions: National diabetes registries confer clear insights into diagnostics, complications, and treatment. The extent to which registries influenced national healthcare policy was less clear. A globally implemented standard outcome set has the potential to improve concordance between national registries, enhance the comparison and exchange of diabetes outcomes, and allocate resources and interventions where most needed.

Published
2021

14. Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice

Author

Meijer, Rick I., Bakker, Wineke, Alta, Caro-Lynn A.F., Sipkema, Pieter, Yudkin, John S., Viollet, Benoit, Richter, Erik A., Smulders, Yvo M., van Hinsbergh, Victor W.M., Serne, Erik H., and Eringa, Etto C.

Subjects
Obesity -- Physiological aspects -- Development and progression, Adipose tissues -- Physiological aspects -- Health aspects, Insulin -- Physiological aspects -- Health aspects, Blood vessels -- Dilatation, Health
Abstract

Microvascular recruitment in muscle is a determinant of insulin sensitivity. Whether perivascular adipose tissue (PVAT) is involved in disturbed insulin-induced vasoreactivity is unknown, as are the underlying mechanisms. This study investigates whether PVAT regulates insulin-induced vasodilation in muscle, the underlying mechanisms, and how obesity disturbs this vasodilation. Insulin-induced vasoreactivity of resistance arteries was studied with PVAT from C57BL/6 or db/db mice. PVAT weight in muscle was higher in db/db mice compared with C57BL/6 mice. PVAT from C57BL/6 mice uncovered insulin-induced vasodilation; this vasodilation was abrogated with PVAT from db/db mice. Blocking adiponectin abolished the vasodilator effect of insulin in the presence of C57BL/6 PVAT, and adiponectin secretion was lower in db/db PVAT. To investigate this interaction further, resistance arteries of [AMPKα2.sup.+/+] and [AMPKα2.sup.-/-] were studied. In [AMPKα2.sup.-/-] resistance arteries, insulin caused vasoconstriction in the presence of PVAT, and [AMPKα2.sup.+/+] resistance arteries showed a neutral response. On the other hand, inhibition of the inflammatory kinase Jun N[H.sub.2]-terminal kinase (JNK) in db/db PVAT restored insulin-induced vasodilation in an adiponectin-dependent manner. In conclusion, PVAT controls insulin-induced vasoreactivity in the muscle microcirculation through secretion of adiponectin and subsequent AMPKα2 signaling. PVAT from obese mice inhibits insulin-induced vasodilation, which can be restored by inhibition of JNK., Obesity is associated with insulin resistance in all organs, including skeletal muscle and the vasculature. The increase of adipose tissue mass in obesity is associated with an altered adipokine secretion [...]

Published
2013
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15. About the Author

Author

Serne, Erik H., primary, Meijer, Rick I., additional, de Boer, Michiel P., additional, de Jongh, Renate T., additional, IJzerman, Richard G., additional, Bakker, Wineke, additional, and Eringa, Etto C., additional

Published
2009
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16. Meal-related increases in microvascular vasomotion are impaired in obese individuals: a potential mechanism in the pathogenesis of obesity-related insulin resistance

Author

Jonk, Amy M., Houben, Alfons J., Schaper, Nicolaas C., de Leeuw, Peter W., Serne, Erik H., Smulders, Yvo M., and Stehouwer, Coen D.

Subjects
Obesity -- Complications and side effects -- Research, Insulin resistance -- Complications and side effects -- Research, Blood circulation disorders -- Risk factors -- Research, Health
Abstract

Obesity is associated with insulin resistance, hypertension, cardiovascular disease, and type 2 diabetes (1), but the mechanisms underlying these associations are incompletely understood. This article reviews and adds original data [...]

Published
2011
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18. Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy

Author

de Jongh, Renate T., Serne, Erik H., IJzerman, Richard G., de Vries, Greetje, and Stehouwer, Coen D.A.

Subjects
Risk factors, Causes of, Obesity -- Risk factors, Hypertension -- Causes of -- Risk factors, Insulin resistance -- Causes of -- Risk factors
Abstract

Obesity is an important contributor to the burden of cardiovascular disease because it increases risk not only of large artery disease (1,2) but also of disease entities that are in [...], To test the hypothesis that free fatty acids (FFAs) modulate microvascular function and that this contributes to obesity-associated insulin resistance, hypertension, and microangiopathy, we examined the effects of both FFA elevation in lean women and FFA lowering in obese women on skin microvascular function. A total of 16 lean and 12 obese women underwent, respectively, Intralipid plus heparin (or saline) infusion and overnight acipimox (or placebo) treatment. We measured capillary recruitment with capillaroscopy and endothelium-(in)dependent vasodilation by iontophoresis of acetylcholine and sodium nitroprusside before and during hyperinsulinemia (40 mU x [m.sup.-2] x [min.sup.-1]). FFA elevation impaired capillary recruitment and acetylcholine-mediated vasodilation before (44.6 ± 16.8 vs. 56.9 ± 18.9%, P < 0.05; and 338 ± 131 vs. 557 ± 162%, P < 0.01, respectively) and during (54.0 ± 21.3 vs. 72.4 ± 25.4%, P < 0.01; and 264 ± 186 vs. 685 ± 199%, P < 0.01, respectively) hyperinsulinemia. FFA lowering improved capillary recruitment before (50.9 ± 14.6 vs. 37.4 ± 9.3%, P < 0.01) and during (66.8 ± 20.6 vs. 54.8 ± 15.4%, P < 0.05) hyperinsulinemia. Changes in FFA levels were inversely associated with changes in capillary recruitment and insulin sensitivity in lean (r = -0.46, P = 0.08; and r = -0.56, P = 0.03) and in obese (r = -0.70, P = 0.02; and r = -0.62, P = 0.04) women. Regression analyses showed that changes in capillary recruitment statistically explained ~29% of the association between changes in FFA levels and insulin sensitivity. In conclusion, FFA levels modulate microvascular function and may contribute to obesity-associated insulin resistance, hypertension, and microangiopathy.

Published
2004

19. Direct evidence for insulin-induced capillary recruitment in skin of healthy subjects during physiological hyperinsulinemia

Author

Serne, Erik H., IJzerman, Richard G., Gans, Reinold O.B., Nijveldt, Robin, de Vries, Greetje, Evertz, Reinder, Donker, Ab J.M., and Stehouwer, Coen D.A.

Subjects
Biological transport -- Research -- Measurement, Diabetes -- Research, Insulin -- Research, Regional blood flow -- Measurement -- Research, Health, Research, Measurement
Abstract

It has been proposed that insulin-mediated changes in muscle perfusion modulate insulin-mediated glucose uptake. However, the putative effects of insulin on the microcirculation that permit such modulation have not been [...]

Published
2002

20. Individualised versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome (IDEAL DVT): a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial

Author

ten Cate-Hoek, Arina J., ten Cate-Hoek, Arina J., Amin, Elham E., Bouman, Annemieke C., Meijer, Karina, Tick, Lidwine W., Middeldorp, Saskia, Mostard, Guy J. M., ten Wolde, Marije, van den Heiligenberg, Simone M., van Wissen, Sanne, van de Poel, Marlene H. W., Villalta, Sabina, Serne, Erik H., Otten, Hans-Martin, Klappe, Edith H., Bistervels, Ingrid M., Lauw, Mandy N., Piersma-Wichers, Margriet, Prandoni, Paolo, Joore, Manuela A., Prins, Martin H., ten Cate, Hugo, IDEAL DVT Investigators, ten Cate-Hoek, Arina J., ten Cate-Hoek, Arina J., Amin, Elham E., Bouman, Annemieke C., Meijer, Karina, Tick, Lidwine W., Middeldorp, Saskia, Mostard, Guy J. M., ten Wolde, Marije, van den Heiligenberg, Simone M., van Wissen, Sanne, van de Poel, Marlene H. W., Villalta, Sabina, Serne, Erik H., Otten, Hans-Martin, Klappe, Edith H., Bistervels, Ingrid M., Lauw, Mandy N., Piersma-Wichers, Margriet, Prandoni, Paolo, Joore, Manuela A., Prins, Martin H., ten Cate, Hugo, and IDEAL DVT Investigators

Abstract

Background Therapy with elastic compression stockings has been the cornerstone for prevention of post-thrombotic syndrome for decades in patients after acute deep venous thrombosis. It is uncertain who benefits most from therapy, and what the optimum duration of therapy should be. We therefore aimed to assess the safety and efficacy of individualised duration of compression therapy versus the standard duration of 24 months following an initial treatment period of 6 months. Methods We did a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial at 12 hospitals in the Netherlands and two in Italy. We randomly assigned patients (1:1) with acute proximal deep vein thrombosis of the leg and without pre-existent venous insufficiency (Clinical Etiological Anatomical and Pathophysiological score

Published
2018

22. The Presence of Cerebral White Matter Lesions and Lower Skin Microvascular Perfusion Predict Decline in General Cognitive Ability in Type 1 Diabetes Patients but Not in Healthy Controls

Author

EMANUEL, ANNA L., primary, DUINKERKEN, EELCO VAN, additional, WATTJES, MIKE P., additional, KLEIN, MARTIN, additional, BARKHOF, FREDERIK, additional, SNOEK, FRANK J., additional, ERINGA, ETTO C., additional, IJZERMAN, RICHARD, additional, and SERNE, ERIK H., additional

Published
2018
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25. Perivascular fat in human muscle

Author

Meijer, Rick I, primary, Serne, Erik H, additional, Yudkin, John S, additional, van Hinsbergh, Victor WM, additional, Smulders, Yvo M, additional, and Eringa, Etto C, additional

Published
2016
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26. Effects of insulin and atrial natriuretic peptide on renal tubular sodium handling in sickle cell disease

Author

TER MAATEN, JAN C., SERNE, ERIK H., VAN EPS, WIM STATIUS, TER WEE, PIETER M., DONKER, AB J. M., and GANS, RIJK O. B.

Subjects
Physiology -- Research, Hemoglobin -- Research, Blood flow -- Analysis, Peptides -- Research, Insulin -- Research, Kidney tubules -- Research, Sickle cell anemia -- Causes of, Biological sciences
Abstract

Ter Maaten, Jan C., Erik H. Serne, Wim Statius van Eps, Pieter M. ter Wee, Ab J. M. Donker, and Rijk O. B. Gans. Effects of insulin and atrial natriuretic peptide on renal tubular sodium handling in sickle cell disease. Am. J. Physiol. Renal Physiol. 278: F499-F505, 2000.--We assessed the effect of insulin and atrial natriuretic peptide (ANP) on renal sodium handling in eight patients with sickle cell disease (SCD), who are characterized by loss of vasa recta and long loops of Henle, and matched control subjects. During insulin infusion (50 mU [multiplied by] [kg.sup.-1] [multiplied by] [h.sup.-1]), fractional sodium excretion decreased by 0.44 [+ or -] 0.72% (P = 0.13) in patients with SCD and by 0.57 [+ or -] 0.34% (P = 0.002) in control subjects, whereas fractional distal sodium reabsorption increased by 4.1 [+ or -] 1.5% (P [is less than] 0.001) and 3.0 [+ or -] 1.5% (P [is less than] 0.001), respectively. Low-dose (0.3 pmol [multiplied by] [kg.sup.-1] [multiplied by] [h.sup.-1]) ANP infusion did not affect renal sodium handling in patients with SCD but increased fractional sodium excretion by 0.34 [+ or -] 0.22% (P = 0.003) in control subjects. High-dose (2 [micro]g/min) ANP increased natriuresis to a similar extent in both groups. Insulin's antinatriuretic effects predominated over the natriuretic effects of low-dose, but not high-dose, ANP. These data suggest that insulin's antinatriuretic effect is localized at a distal tubular site other than the long loops of Henle and that the long loops are involved in the natriuretic effect of low-dose ANP, possibly mediated by changes in medullary blood flow. loop of Henle; sickle hemoglobin; lithium; medullary blood flow

Published
2000

27. Microvascular Dysfunction: A Potential Mechanism in the Pathogenesis of Obesity-associated Insulin Resistance and Hypertension

Author

de Boer, Michiel P., Meijer, Rick I., Wijnstok, Nienke J., Jonk, Amy M., Houben, Alphons J. H. M., Stehouwer, Coen D., Smulders, Yvo M., Eringa, Etto C., Serne, Erik H., Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), and RS: CARIM School for Cardiovascular Diseases

Subjects
obesity, hypertension, diabetes, microvascular dysfunction, insulin resistance
Abstract

The intertwined epidemics of obesity and related disorders such as hypertension, insulin resistance, type 2 diabetes, and subsequent cardiovascular disease pose a major public health challenge. To meet this challenge, we must understand the interplay between adipose tissue and the vasculature. Microvascular dysfunction is important not only in the development of obesity-related target-organ damage but also in the development of cardiovascular risk factors such as hypertension and insulin resistance. The present review examines the role of microvascular dysfunction as an explanation for the associations among obesity, hypertension, and impaired insulin-mediated glucose disposal. We also discuss communicative pathways from adipose tissue to the microcirculation.

Published
2012

29. Insuline resistentie

Author

Serne, Erik H., Maaten, ter, J.C., Gans, Reinold O.B., Birkenhager, W.H., de Leeuw, P.W., Lifelong Learning, Education & Assessment Research Network (LEARN), Lifestyle Medicine, and Kidney Health Institute - Khis

Published
2003

30. Rapid Decrease in Delivery of Chemotherapy to Tumors after Anti-VEGF Therapy : Implications for Scheduling of Anti-Angiogenic Drugs

Author

van der Veldt, Astrid A. M., Lubberink, Mark, Bahce, Idris, Walraven, Maudy, de Boer, Michiel P., Greuter, Henri N. J. M., Hendrikse, N. Harry, Eriksson, Jonas, Windhorst, Albert D., Postmus, Pieter E., Verheul, Henk M., Serne, Erik H., Lammertsma, Adriaan A., Smit, Egbert F., van der Veldt, Astrid A. M., Lubberink, Mark, Bahce, Idris, Walraven, Maudy, de Boer, Michiel P., Greuter, Henri N. J. M., Hendrikse, N. Harry, Eriksson, Jonas, Windhorst, Albert D., Postmus, Pieter E., Verheul, Henk M., Serne, Erik H., Lammertsma, Adriaan A., and Smit, Egbert F.

Abstract

Current strategies combining anti-angiogenic drugs with chemotherapy provide clinical benefit in cancer patients. It is assumed that anti-angiogenic drugs, such as bevacizumab, transiently normalize abnormal tumor vasculature and contribute to improved delivery of subsequent chemotherapy. To investigate this concept, a study was performed in non-small cell lung cancer (NSCLC) patients using positron emission tomography (PET) and radiolabeled docetaxel ([11C]docetaxel). In NSCLC, bevacizumab reduced both perfusion and net influx rate of [11C]docetaxel within 5 hr. These effects persisted after 4 days. The clinical relevance of these findings is notable, as there was no evidence for a substantial improvement in drug delivery to tumors. These findings highlight the importance of drug scheduling and advocate further studies to optimize scheduling of anti-angiogenic drugs.

Published
2012
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36. Effects of insulin and atrial natriuretic peptide on renal tubular sodium handling in sickle...

Author

Maaten, Jan C. Ter and Serne, Erik H.

Subjects
*INSULIN, *ATRIAL natriuretic peptides, *PHYSIOLOGY
Abstract

Assesses the tubular localization of the effects of insulin and two doses of atrial natriuretic peptide (ANP) on renal sodium handling in patients with sickle cell disease and normal control subjects. Interaction of insulin and ANP regarding renal sodium handling by concomitant infusion of both hormones in each group of subjects.

Published
2000
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38. Protein kinase C theta activation induces insulin-mediated constriction of muscle resistance arteries.

Author

Bakker W, Sipkema P, Stehouwer CD, Serne EH, Smulders YM, van Hinsbergh VW, and Eringa EC

Subjects
Animals, Arteries physiology, Endothelin-1 metabolism, Humans, Isoenzymes genetics, Mice, Mice, Knockout, Mitogen-Activated Protein Kinase 3 metabolism, Mitogen-Activated Protein Kinase 6 metabolism, Nitric Oxide metabolism, Palmitic Acid pharmacology, Protein Kinase C genetics, Protein Kinase C-theta, Proto-Oncogene Proteins c-akt metabolism, Arteries drug effects, Insulin pharmacology, Isoenzymes metabolism, Muscle, Skeletal blood supply, Protein Kinase C metabolism, Vasoconstriction drug effects
Abstract

Objective: Protein kinase C (PKC) theta activation is associated with insulin resistance and obesity, but the underlying mechanisms have not been fully elucidated. Impairment of insulin-mediated vasoreactivity in muscle contributes to insulin resistance, but it is unknown whether PKC theta is involved. In this study, we investigated whether PKC theta activation impairs insulin-mediated vasoreactivity and insulin signaling in muscle resistance arteries., Research Design and Methods: Vasoreactivity of isolated resistance arteries of mouse gracilis muscles to insulin (0.02-20 nmol/l) was studied in a pressure myograph with or without PKC theta activation by palmitic acid (PA) (100 micromol/l)., Results: In the absence of PKC theta activation, insulin did not alter arterial diameter, which was caused by a balance of nitric oxide-dependent vasodilator and endothelin-dependent vasoconstrictor effects. Using three-dimensional microscopy and Western blotting of muscle resistance arteries, we found that PKC theta is abundantly expressed in endothelium of muscle resistance arteries of both mice and humans and is activated by pathophysiological levels of PA, as indicated by phosphorylation at Thr(538) in mouse resistance arteries. In the presence of PA, insulin induced vasoconstriction (21 +/- 6% at 2 nmol/l insulin), which was abolished by pharmacological or genetic inactivation of PKC theta. Analysis of intracellular signaling in muscle resistance arteries showed that PKC theta activation reduced insulin-mediated Akt phosphorylation (Ser(473)) and increased extracellular signal-related kinase (ERK) 1/2 phosphorylation. Inhibition of PKC theta restored insulin-mediated vasoreactivity and insulin-mediated activation of Akt and ERK1/2 in the presence of PA., Conclusions: PKC theta activation induces insulin-mediated vasoconstriction by inhibition of Akt and stimulation of ERK1/2 in muscle resistance arteries. This provides a new mechanism linking PKC theta activation to insulin resistance.

Published
2008
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