The heritability of HbA1c and fasting blood glucose in different measurement settings.

In an extended twin study we estimated the heritability of fasting HbA1c and blood glucose levels. Blood glucose was assessed in different settings (at home and in the clinic). We tested whether the genetic factors influencing fasting blood glucose levels overlapped with those influencing HbA1c and whether the same genetic factors were expressed across different settings. Fasting blood glucose was measured at home and during two visits to the clinic in 77 healthy families with same-sex twins and siblings, aged 20 to 45 years. HbA1c was measured during the first clinic visit. A 4-variate genetic structural equation model was used that estimated the heritability of each trait and the genetic correlations among traits. Heritability explained 75% of the variance in HbA1c. The heritability of fasting blood glucose was estimated at 66% at home and lower in the clinic (57% and 38%). Fasting blood glucose levels were significantly correlated across settings (0.34 < r < 0.54), mostly due to a common set of genes that explained between 53% and 95% of these correlations. Correlations between HbA1c and fasting blood glucoses were low (0.11 < r < 0.23) and genetic factors influencing HbA1c and fasting glucose were uncorrelated. These results suggest that in healthy adults the genes influencing HbA1c and fasting blood glucose reflect different aspects of the glucose metabolism. As a consequence these two glycemic parameters can not be used interchangeably in diagnostic procedures or in studies attempting to find genes for diabetes. Both contribute unique (genetic) information

Health-related quality of life in adrenocortical carcinoma:Development of the disease-specific questionnaire ACC-QOL and results from the PROFILES registry

We aimed to develop a disease-specific adrenocortical carcinoma (ACC) health-related quality of life (HRQoL) questionnaire (ACC-QOL) and assess HRQoL in a population-based cohort of patients with ACC. Development was in line with European Organization for Research and Treatment of Cancer (EORTC) guidelines, though not an EORTC product. In phase I and II, we identified 90 potential HRQoL issues using literature and focus groups, which were reduced to 39 by healthcare professionals. Pilot testing resulted in 28 questions, to be used alongside the EORTC QLQ-C30. In Phase III, 100 patients with ACC were asked to complete the questionnaires twice in the PROFILES registry (3-month interval, respondents: first 67, second 51). Confirmatory factor analysis demonstrated the structural validity of 26 questions with their scale structure (mitotane side-effects, hypercortisolism/hydrocortisone effects, emotional effects). Internal consistency and reliability were good (Cronbach's alpha 0.897, Interclass correlation coefficient 0.860). Responsiveness analysis showed good discriminative ability (AUC 0.788). Patients diagnosed more than 5 years ago reported a good HRQoL compared with the Dutch reference population, but experienced residual fatigue and emotional problems. Patients who underwent recent treatment reported a lower HRQoL and problems in several domains. In conclusion, we developed an ACC-specific HRQoL questionnaire with good psychometric properties

Circulating adrenomedullin and B-type natriuretic peptide do not predict blood pressure fluctuations during pheochromocytoma resection: a cross-sectional study

Background: Despite adequate presurgical management, blood pressure fluctuations are common during resection of pheochromocytoma or sympathetic paraganglioma (PPGL). To a large extent, the variability in blood pressure control during PPGL resection remains unexplained. Adrenomedullin and B-type natriuretic peptide, measured as MR-proADM and NT-proBNP, respectively, are circulating biomarkers of cardiovascular dysfunction. We investigated whether plasma levels of MR-proADM and NT-proBNP are associated with blood pressure fluctuations during PPGL resection. Methods: Study subjects participated in PRESCRIPT, a randomized controlled trial in patients undergoing PPGL resection. MR-proADM and NT-proBNP were determined in a single plasma sample drawn before surgery. Multivariable linear and logistic regression analyses were used to explore associations between these biomarkers and blood pressure fluctuations, use of vasoconstrictive agents during surgery as well as the occurrence of perioperative cardiovascular events. Results: A total of 126 PPGL patients were included. Median plasma concentrations of MR-proADM and NT-proBNP were 0.51 (0.41-0.63) nmol/L and 68.7 (27.9-150.4) ng/L, respectively. Neither MR-proADM nor NT-proBNP were associated with blood pressure fluctuations. There was a positive correlation between MR-proADM concentration and the cumulative dose of vasoconstrictive agents (03B2 0.44, P = 0.001). Both MR-proADM and NT-proBNP were significantly associated with perioperative cardiovascular events (OR: 5.46, P = 0.013 and OR: 1.54, P = 0.017, respectively). Conclusions: plasma MR-proADM or NT-proBNP should not be considered as biomarkers for the presurgical risk assessment of blood pressure fluctuations during PPGL resection. Future studies are needed to explore the potential influence of these biomarkers on the intraoperative requirement of vasoconstrictive agents and the perioperative cardiovascular risk.Diabetes mellitus: pathophysiological changes and therap

Fibrodysplasia ossificans progressiva: what have we achieved and where are we now?: Follow-up to the 2015 Lorentz workshop

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare progressive genetic disease effecting one in a million individuals. During their life, patients with FOP progressively develop bone in the soft tissues resulting in increasing immobility and early death. A mutation in the ACVR1 gene was identified as the causative mutation of FOP in 2006. After this, the pathophysiology of FOP has been further elucidated through the efforts of research groups worldwide. In 2015, a workshop was held to gather these groups and discuss the new challenges in FOP research. Here we present an overview and update on these topics.Diabetes mellitus: pathophysiological changes and therap

Bisfosfonaatgerelateerde osteonecrose van de kaak

Bisfosfonaatgerelateerde osteonecrose van de kaak is een complicatie die zich kan voordoen bij patiënten die zijn behandeld met bisfosfonaten. De pathogenese is niet geheel duidelijk. Predisponerende factoren zijn invasieve behandelingen in de mond, waarvan gebitsextractie het grootste risico vormt. Gelet op de complexiteit van de behandeling van deze kaakbotnecrose is preventie uiterst belangrijk. Noodzakelijke invasieve behandelingen in de mond moeten bij voorkeur worden uitgevoerd voordat wordt begonnen met het gebruik van bisfosfonaten. Aangezien deze vorm van osteonecrose relatief zelden voorkomt, is het begrijpelijk dat de richtlijnen betreffende preventie en behandeling niet zijn gebaseerd op wetenschappelijk bewijs

Een adolescente jongen met fibreuze dysplasie van het kaakbot

Een 16-jarige jongen bleek na diagnostisch onderzoek met computertomografie en een skeletscan de monostotische verschijningsvorm van fibreuze dysplasie in de maxilla te hebben. De diagnose is bevestigd aan de hand van een botbiopt. Tijdens een periode van 8 jaar afwachtend beleid hebben zich geen tekenen van progressie van de afwijking voorgedaan. Fibreuze dysplasie is een enigszins onbegrepen, benigne botafwijking die overal in het skelet kan voorkomen. Om de diagnose met zekerheid te kunnen stellen, wordt over het algemeen geadviseerd een botbiopt te nemen. Er wordt onderscheid gemaakt tussen 3 verschijningsvormen: 1. monostotisch, 2. polyostotisch en 3. polyostotisch met endocriene problemen. In de meeste gevallen kan worden volstaan met een afwachtend beleid. Maligne ontaarding is uiterst zeldzaam en doet zich vrijwel uitsluitend voor bij de polyostotische verschijningsvorm