Lipids and apolipoproteins in cardiovascular disease

Lipids and apolipoproteins in cardiovascular disease
PhD ceremony: P.J.W.H. Kappelle, MSc
When: December 14, 2016
Start: 09:00
Where: Academy building RUG
Faculty: Medical Sciences / UMCG
Promotor: prof. dr. B.H.R. (Bruce) Wolffenbuttel


The first part of this thesis describes the role of cholesterol particles and associated proteins, and their role in the development of cardiovascular disease. There seems to be an advantage in determining the balance between good and bad cholesterol, as compared to the separate measures when attempting to predict the development of cardiovascular disease. Certain genes that have an influence on proteins transporting cholesterol from one particle to the other, do not seem to have an effect on the predictive value of these measures. The inhibition of this protein does increase the level of the good cholesterol, but this does not seem to result in any survival benefit.

The second part of this thesis describes the effect of cholesterol lowering agents on different cholesterol particles and associated proteins. Cholesterol lowering agents seem to affect the number of particles less than their cholesterol content. This could lead to a lack of intensive cholesterol treatment when only the cholesterol concentration is considered.

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Thyroid cancer treatment

Thyroid cancer treatment
Long-term effects and new developments
PhD ceremony: Ms E.N. (Esther) Klein Hesselink
When: October 12, 2016
Start: 16:15
Promotor: prof. dr. T.P. Links
Where: Academy building RUG
Faculty: Medical Sciences / UMCG

Thyroid cancer is increasingly common. This is especially the case for differentiated thyroid cancer (DTC), which has a favorable prognosis. Treatment consists of surgical removal of the thyroid gland, radioiodine treatment, and life-long administration of relatively high doses of thyroid hormone. This treatment is effective, but also rather aggressive since it can result in the occurrence of both short- and long-term adverse effects. There used to be little attention for this issue, as cancer-related outcome was less favorable. Nowadays, we see a lot of DTC patients with small tumors who have a near-normal life expectancy. For these patients long-term adverse effects of treatment are very important since they can negatively impact quality of life.

In this thesis we therefore studied the occurrence of long-term effects of DTC treatment. We found that atrial fibrillation (a cardiac rhythm disturbance) and mortality due to cardiovascular diseases are more common in DTC patients as compared to the general population. Furthermore, we found that a part of patients have salivary glands dysfunction following radioiodine treatment. Fortunately, the adverse effects of treatment on bone marrow function were limited.

Furthermore, there is a small group of thyroid cancer patients with more aggressive disease. For these patients, cure is often not achievable. Therefore, we studied the efficacy and toxicity of tyrosine kinase inhibitors (a new class of drugs) that have been studied in these patients. In addition, we studied the hereditary material of several thyroid cancers in an attempt to understand more of thyroid cancer pathogenesis.

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Behandeling met GLP1-receptor agonist kosten-effectief

ScreenHunter_248 Jul. 04 16.12

The cost-effectiveness of exenatide twice daily (BID) versus insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes
Authors: J. Gordon, P. McEwan, U. Sabale, B. Kartman & B.H.R Wolffenbuttel

Objective: To evaluate the cost-effectiveness of exenatide twice daily (BID) versus bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is suboptimal with titrated basal insulin glargine and metformin.
Methods: The analysis was based on the recent 4B Study, which compared exenatide BID and lispro TID as add-on therapies in subjects with type 2 diabetes insufficiently controlled despite titrated insulin glargine. The Cardiff Diabetes Model was used to simulate patient costs and health benefits beyond the 4B Study. The Swedish healthcare perspective was adopted for this analysis; costs are reported in €EUR to aid interpretation. The main outcome measure was the cost per quality-adjusted life-year (QALY) gained with exenatide BID compared to lispro TID.
Results: Exenatide BID was associated with an incremental cost of €1,270 and a QALY increase of +0.64 compared with lispro TID over 40 years. The cost per QALY gained with exenatide BID compared with lispro TID was €1,971, which is within conventional limits of cost-effectiveness. Cost-effectiveness results were generally robust to alternative assumptions and values for key model parameters.
Limitations: Extrapolation of trial data over the longer term can be influenced by modelling and parameter uncertainty. Cost-effectiveness results were generally insensitive to alternative values of key model input parameters and across scenarios.
Conclusions: The addition of exenatide BID rather than insulin lispro to basal insulin is associated with similar or better clinical outcomes. Illustrated from the Swedish healthcare perspective, analysis with the Cardiff Diabetes Model demonstrated that exenatide BID represents a cost-effective treatment alternative to lispro TID as add-on therapy in type 2 diabetes patients insufficiently controlled on basal insulin.



Subsidie DiabetesFonds voor bestuderen ‘endocrine disruptors’ en diabetes

Onderzoekers UMCG krijgen subsidie Diabetesfonds voor ontrafelen mechanismen diabetes

Onderzoekers van het UMCG ontvangen een subsidie van 275.000 euro van het Diabetesfonds. Met dit geld gaat Jana van Vliet-Ostaptchouk van de afdeling Endocrinologie onderzoek doen naar verstoringen van het endocriene systeem in het lichaam, die worden veroorzaakt door blootstelling aan bepaalde milieuverontreinigende stoffen. Haar onderzoek richt zich vooral op het zichtbaar maken van de onderliggende mechanismen van het ontstaan van diabetes.

diabetes photoDe huidige epidemie van type2-diabetes (T2D) vormt een belangrijk risico voor de moderne samenleving. Recente gegevens wijzen erop dat blootstelling aan bepaalde milieuverontreinigende stoffen, zogeheten endocriene disruptors (EDC), een belangrijke rol kan spelen in de wereldwijde toename van diabetes. Onderzoek laat zien dat EDC het endocriene systeem in het lichaam op diverse manieren verstoren.

Van Vliet-Ostaptchouk wil in haar onderzoek de relatie tussen EDC, verstoring van de glucosestofwisseling en verhoogd risico op type2-diabetes nagaan. Tevens wil zij nagaan of dit risico verandert door genetische aanleg en leefstijl. Zij vergelijkt de bloostellingen aan EDC’s en de interactie met erfelijke factoren en voedingsgewoonten en hoeveelheid lichaamsbeweging, tussen gezonde mensen, mensen met overgewicht en een groep van 1500 patiënten met type2-diabetes.

Voor haar onderzoek maakt Van Vliet gebruik van de gegevens van de LifeLines-biobank. Het onderzoek wordt uitgevoerd in samenwerking met Dr. A.M. Andersson van het Center of Endocrine Disruptors, Copenhagen University Hospital. Mede-aanvrager voor de subsidie is Prof. B. Wolffenbuttel van het UMCG. De studie gaat in totaal 4 jaar duren.

23 juni 2014

Photo by GDS Infographics

Gunstige cardiovasculaire effecten van liraglutide


Recent zijn de resultaten van de eerste studie naar de cardiovasculaire benefits van behandeling met een GLP1RA gepresenteerd op het Amerikaanse Diabetes Congres, en gepubliceerd in het New England Journal of Medicine.

Een korte samenvatting van de studie:
The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown.
In a double-blind trial, randomly assigned patients with type 2 diabetes and high cardiovascular risk were to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes.
In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo.

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Bijniernet website steeds professioneler en completer

adrenalBijnierNET is een platform voor zorgaanbieders, patiënten, mantelzorgers en geïnteresseerden rondom de Bijnieraandoeningen: Bijnierschorsinsufficiëntie (Addison), Syndroom van Cushing, AGS, Primair Hyperaldosteronisme (Ziekte van Conn),  Feochromocytoom en Bijnierschorscarcinoom.

De zorg voor patiënten met zeldzame bijnieraandoeningen is van oudsher specialistisch, complex, kostbaar en arbeidsintensief. Er bestaat slechts beperkt inzicht in de organisatie, het proces en de uitkomsten van deze zorg. Teneinde de zorg voor deze bijzondere groep patiënten te verbeteren, hebben de participanten in het BijnierNET de mogelijkheden die een landelijke (digitale) community hiervoor met zich meebrengen nader uitgezocht. In het BijnierNET kunnen patiënten, zorgverleners en mantelzorgers elkaar (virtueel) ontmoeten, ervaringen uitwisselen en de kennis rond de zorg voor bijnierpatiënten – ook bij afnemend zorgaanbod – op een hoog peil behouden, mogelijk op een hoger peil brengen.

Door een betere verspreiding van de beschikbare kennis bij/van alle deelnemers kan goede zorg beschikbaar blijven.Deze inbreng van kennis kan mogelijk kostenbesparend gaan werken.


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