Gestational diabetes mellitus: diagnosis and outcome.
Need for a revision of the Dutch perspective?
PhD ceremony: S.H. Koning, MSc
When: November 27, 2017
Promotors: prof. dr. B.H.R. (Bruce) Wolffenbuttel, P.P. van den Berg
Where: Academy building RUG, open to the public
Faculty: Medical Sciences / UMCG
Untreated gestational diabetes mellitus (GDM) is associated with an increased risk of complications for both mother and child. Many of these complications can be reduced by early diagnosis and treatment of GDM. However, worldwide there is a lack of agreement on the best way to diagnose and treat GDM.
In the Netherlands, the Dutch Society of Obstetrics and Gynaecology guideline “Diabetes and Pregnancy” for the screening and treatment of GDM was implemented in 2010. The diagnostic thresholds are based on the old WHO consensus originating from 1999 and have until now not been updated to the newest (more stringent) criteria, implemented in 2013. These new criteria have been adopted by many expert committees. However, evidence that applying the stricter criteria for GDM improves pregnancy outcomes is limited.
The research described in this thesis aimed to evaluate the current Dutch national guideline of GDM i.e. what is the outcome of GDM pregnancies using this guideline? And what are consequences when the current diagnostic criteria of GDM are to be revised?
In this thesis we have shown that the currently used national guideline for screening and treatment of GDM is successful in reducing the risk of short-term adverse outcomes, but not in reducing the likelihood of having a large-for-gestational-age neonate. We have also shown that the long-term care for GDM is far from optimal and requires further improvement. In order to further optimize GDM care and pregnancy outcomes we advise the use of more stringent blood glucose criteria for GDM diagnosis.
Background: Early diagnosis and treatment of high blood pressure (BP) and cholesterol is important to reduce cardiovascular risk. We compared BP and LDL-cholesterol (LDL-C) as well as the quality of treatment between obese subjects and normal weight and overweight individuals.
Methods: 87,648 participants of the Lifelines study were categorised according to obesity (normal weight/ overweight/obesity) and age. Mean systolic BP and LDL-C were calculated depending on treatment, BMI, age and sex.
Results: In all age groups, except those aged 70-80 years, women had a significantly lower BP than men. Use of BP-lowering medication did not result in BP levels comparable with non-users, except in those aged 70-80 years. Despite medication, the BP was insufficiently controlled in 20-50% of participants. BP was significantly higher in obese vs. normal weight and overweight individuals of all ages, but most apparently in men younger than 50 years. Mean LDL-C varied between 2.5- .0 mmol/l. Despite higher statin use, obese participants had a higher LDL-C than those with a normal weight. Statins abolished the age-dependent LDL-C increase. Many participants did not achieve target LDL-C < 2.5 mmol/l. A small percentage of individuals treated with BP-lowering drugs were also using statins (overall 32% in men, 17% in women).
Conclusion: Obese individuals, especially men younger than 50, have a higher BP and LDL-C compared with those with overweight and a normal weight. Use of BP-lowering drugs did not revert the BP back to levels normal for the specific age and BMI group, whereas statins abolished the age-related increase in LDL-C. These data suggest that more attention is needed for active screening and treatment of cardiovascular risk factors.
Read the full article at: http://www.njmonline.nl/getpdf.php?id=1911
Introduction and aim: Insight into the total economic burden of diabetes mellitus (DM) is essential for decision makers and payers. Currently available estimates for the Netherlands only include part of the total burden or are no longer up-to-date. Therefore, this study aimed to determine the current total economic burden of DM and its complications in the Netherlands, by including all the relevant cost components.
Methods: The study combined a systematic literature review to identify all relevant published information and a targeted review to identify relevant information in the grey literature. The identified evidence was then combined to estimate the current total economic burden.
Results: In 2016, there were an estimated 1.1 million DM patients in the Netherlands, of whom approximately 10% had type 1 and 90% had type 2 DM. The estimated current total economic burden of DM was € 6.8 billion in 2016. Healthcare costs (excluding costs of complications) were € 1.6 billion, direct costs of complications were € 1.3 billion and indirect costs due to productivity losses, welfare payments and complications were € 4.0 billion.
Conclusion: DM and its complications pose a substantial economic burden to the Netherlands, which is expected to rise due to changing demographics and lifestyle. Indirect costs, such as welfare payments, accounted for a large portion of the current total economic burden of DM, while these cost components are often not included in cost estimations. Publicly available data for key cost drivers such as complications were scarce.
Read the full article at: http://www.njmonline.nl/getpdf.php?id=1883
Epidemiology of metabolic health
Lifestyle determinants and health-related quality of life
PhD ceremony: S.N. Slagter
When: January 11, 2017
Promotor: prof. dr. B.H.R. (Bruce) Wolffenbuttel
Where: Academy building RUG, open to the public.
Faculty: Medical Sciences / UMCG
Overweight and obesity often lead to the development of a disturbed glucose metabolism, increased blood pressure and a disturbed fat profile (too low values of the “good” HDL-cholesterol and high triglycerides values). This combination of metabolic complications is called the metabolic syndrome. It is associated with an increased risk of type 2 diabetes and cardiovascular diseases. Approximately one in four Europeans have the metabolic syndrome. Even though it is usually caused by obesity, a sub-group of obese people seem to be less susceptible to the metabolic health risks. They have an equally healthy metabolism as lean people. In the literature, this is referred to as metabolically healthy obese.
In ten large population studies from seven different European countries the occurrence of the metabolic syndrome and metabolically healthy obesity has been estimated. The metabolic syndrome is common in Europe and the Netherlands. However, in the Dutch LifeLines study still nearly 1 out of 4 obese women and 1 out of 10 obese men are metabolically healthy (depending on their age). From studies with LifeLines data only, it seems that smoking-, drinking-, eating- and exercise behaviours of these people is important. The level of tobacco use and drinking more than one alcoholic beverage per day was already related to the development of the metabolic syndrome. However, a ‘healthy’ dietary pattern and intensive vigorous physical activity increased in obese people the chance of metabolically healthy obesity. Actively changing lifestyle factors will reduce the number of people developing the metabolic syndrome, and consequently will reduce the incidence of type 2 diabetes and cardiovascular diseases. However, even before these more serious chronic conditions occur, obese subjects (without metabolic complications) had an impaired quality of life. Therefore, in the treatment of obesity it is advisable to take into account aspects relating to the quality of life.
Erfelijke stofwisselingsziekten is een groep aangeboren aandoeningen waarbij er sprake is van een defect in een enzym, cofactor of transporter. Hierdoor ontstaat een stoornis in het koolhydraat-, vet- of eiwitmetabolisme, of in de synthese of afbraak van complexe moleculen. Er zijn momenteel ruim 800 erfelijke metabole ziekten beschreven, waarvan de meeste zeldzaam tot uiterst zeldzaam zijn. Er wordt echter geschat dat ten minste 1 op de 2500 levendgeborenen een stofwisselingsziekte heeft.
Voorheen waren erfelijke stofwisselingsziekten bij uitstek het terrein van de kinderarts en dit specialisme erkent dan ook het aandachtsgebied metabole ziekten. Door verbeterde zorg, uitbreiding van de diagnostische mogelijkheden en toegenomen bewustwording (‘awareness’) van erfelijke metabole aandoeningen, neemt het aantal volwassenen met een erfelijke stofwisselingsziekte sterk toe. Het zeldzame voorkomen en de specifieke problemen die zich op volwassen leeftijd voordoen maakt dat gespecialiseerde zorg voor hen belangrijk is. De zorg voor volwassenen heeft zijn eigen specifieke uitdagingen, zoals de zorg voor patiënten met een erfelijke stofwisselingsziekte tijdens de zwangerschap. Langdurig vasten, bijvoorbeeld rond een chirurgische ingreep, kan leiden tot levensbedreigende metabole ontregeling, vooral wanneer de nodige voorzorgsmaatregelen niet zijn genomen.
Het aantal patiënten met aangeboren afwijkingen van de stofwisseling dat wordt verwezen naar onze polikliniek, neemt gestaag toe. Sommige van deze patiënten worden doorverwezen door Kindergeneeskunde vanwege het feit dat ze de volwassenheid hebben bereikt, maar anderen zijn doorverwezen door hun huisarts en de regionale ziekenhuizen.
De meest voorkomende diagnoses bij de patiënten die we in onze polikliniek begeleiden, zijn: mitochondriale ademhalingsketen aandoeningen, galactosemie, vitamine B12 tekort en aanverwante stoornissen, glycogeen stapeling, fenylketonurie, en stoornissen van de vetzuurstofwisseling zoals MCADD. In het UMCG wordt nauw samengewerkt met de pediatrische afdeling ‘metabole ziekten’.
In Nederland en België wordt door de diverse (academische) afdelingen nauw samengewerkt. U vindt hierover informatie op de website www.investof.nl, die wordt bijgehouden door de collega’s van het AMC (dr. Linthorst). Nog meer informatieover stofwisselingsziekten vindt u in dit artikel in het Nederlands Tijdschrift voor Geneeskunde: https://www.ntvg.nl/artikelen/volwassenen-met-een-erfelijke-stofwisselingsziekte/icmje
En natuurlijk op goede en informatieve websites als:
mitochondriale aandoeningen: www.mitoinfo.nl
Radboud Center for Mitochondrial Medicine: www.rcmm.info
Lipids and apolipoproteins in cardiovascular disease
PhD ceremony: P.J.W.H. Kappelle, MSc
When: December 14, 2016
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.
For more information: http://www.rug.nl/research/portal/en/publications/lipids-and-apolipoproteins-in-cardiovascular-disease(431d2a57-3e66-4136-bfff-0198e09914d7).html
Thyroid cancer treatment
Long-term effects and new developments
PhD ceremony: Ms E.N. (Esther) Klein Hesselink
When: October 12, 2016
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.
For more information: http://www.rug.nl/research/portal/en/publications/thyroid-cancer-treatment(c182a5fa-f154-459e-ad70-1c137df8c142).html
In de afgelopen jaren bleek regelmatig dat mensen met een bijnierziekte verschillende instructies ontvingen van hun behandelaars hoe om te gaan met stress. Dit kan ernstige gevolgen hebben omdat het verwarring veroorzaakt en direct van invloed kan zijn op het welzijn van de patiënt en zijn naasten. Daarom is – onder de paraplu van het BijnierNET – in 2015 een nieuwe uniforme stressinstructie gemaakt, samen met diverse internist-endocrinologen, verpleegkundig specialisten en patiënten, voor die gevallen dat de patiënt thuis of onderweg niet goed wordt en er een bijniercrisis dreigt. Ook vanuit het UMCG is hieraan intensief meegewerkt. De nieuwe stressinstructie is verkrijgbaar via uw behandelend internist-endocrinoloog, maar kan ook gedownload worden via de website van Bijniernet.
Effects of radioiodine treatment on salivary gland function in patients with differentiated thyroid carcinoma: a prospective study
Authors: Esther N. Klein Hesselink1, Adrienne H. Brouwers1, Johan R. de Jong1, Anouk N.A. van der Horst-Schrivers1, Rob P. Coppes1, Joop D. Lefrandt1, Piet L. Jager2, Arjan Vissink1 and Thera P. Links1
1 University of Groningen, University Medical Center Groningen, Netherlands;
2 Isala Hospital, Zwolle
For correspondence or reprints contact: Thera P. Links, University of Groningen, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, Groningen 9700 RB, Netherlands. E-mail: firstname.lastname@example.org
Introduction: Complaints of a dry mouth (xerostomia) and sialoadenitis are frequent side effects of radioiodine treatment in differentiated thyroid cancer (DTC) patients. However, detailed prospective data on alterations in salivary gland functioning after radioiodine treatment (131I) are scarce. Therefore, the primary aim of this study was to prospectively assess the effect of high-activity radioiodine treatment on stimulated whole saliva flow rate. Secondary aims were to study unstimulated whole and stimulated glandular (i.e., parotid and submandibular) saliva flow rate and composition alterations, development of xerostomia, characteristics of patients at risk for salivary gland dysfunction, and whether radioiodine uptake in salivary glands on diagnostic scans correlates to flow rate alterations.
Methods: In a multicenter prospective study, whole and glandular saliva were collected both before and five months after radioiodine treatment. Furthermore, patients completed the validated xerostomia inventory (XI). Alterations in salivary flow rate, composition and XI score were analyzed. Salivary gland radioiodine uptake on diagnostic scans was correlated with saliva flow rate changes after radioiodine treatment.
Results: Sixty-seven patients (mean age 48±17 years, 63% female, 84% underwent ablation therapy) completed both study visits. Stimulated whole saliva flow rate decreased after ablation therapy (from 0.92 [IQR 0.74-1.25] to 0.80 [0.58-1.18] ml/min, P = .003), as well as unstimulated whole- and stimulated glandular flow rates (p<.05). The concentration of salivary electrolytes was similar at both study visits, whereas the output of proteins, especially amylase (p<.05), was decreased. The subjective feeling of dry mouth increased (P = 0.001). Alterations in saliva flow rate were not associated with (semi)-quantitatively assessed radioiodine uptake in salivary glands on diagnostic scans. For the small cohort of patients undergoing repeat radioiodine therapy, we could not demonstrate alterations in salivary parameters.
Conclusion: We prospectively showed that salivary gland function is affected after high-activity radioiodine ablation therapy in patients with DTC. Therefore, more emphasis should be placed on salivary gland dysfunction during follow-up for DTC patients receiving high-activity radioiodine treatment.
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.