Diagnosis of Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is associated with a high risk of obstetric and neonatal complications. Adequate diagnosis and appropriate treatment are key to prevention of these complications. Most international guidelines have adopted the IADPSG 2010/WHO 2013 diagnostic criteria, for the diagnosis of GDM by recommending the following glycemic thresholds for a 75 g OGTT: fasting plasma glucose value =5.1 mmol/l (92 mg/dl); 1-h value =10.0 mmol/l (180 mg/dl); and 2-h value =8.5 mmol/l (153 mg/dl). These specific cut-off values were chosen because they predict a 75% higher chance of adverse pregnancy outcomes compared to normal glucose values. Some countries have adopted either higher levels for fasting glucose (5.6 or 7.0 mmol/l) or lower levels for 2-h post-OGTT glucose (7.8 mmol/l). There still is some debate whether it is desirable to lower the diagnostic 2-h glucose thresholds to =7.5 mmol/l for Caucasian women and =7.2 mmol/l for women from South Asian background. Several studies have shown that about 20-30% (depending on the applied diagnostic criteria) of the women screened for GDM had/have abnormal OGTT results, necessitating referral, active counseling, and treatment. By adopting the new IADPSG/WHO diagnostic criteria, the prevalence of GDM has increased, which has a major impact on the costs and the capacity of healthcare systems. Screening for GDM may follow either a one-step or a two-step approach. In the one-step approach, GDM is diagnosed based on the results of a single 75 g OGTT. The two-step screening strategy makes use of a non-fasting 50 g glucose challenge test (GCT), whereby an abnormal test result (i.e., a 1-h plasma glucose value =7.8 mmol/l) is followed by a 100 g OGTT. There also is no international consensus on whether universal or risk factor-based screening is preferred. Universal screening implies that all pregnant women will undergo screening between 24 and 28 weeks of pregnancy, while in selective screening, only women who have specific risk factors for developing GDM or who exhibit a possible consequence of hyperglycemia, i.e., macrosomia or polyhydramnios, will undergo an OGTT. Most studies comparing these strategies have mainly reported data on GDM classification, not on GDM treatment or, even better, pregnancy outcomes. Some countries, therefore, follow a hybrid approach of partly risk factor-based and partly universal screening. Recently published systematic economic evaluations support universal screening and the one-step approach as a more likely cost-effective strategy.</p

Vitamin B12

What is vitamin B12? Vitamin B12 (cobalamin) is a water soluble vitamin required for several physiological processes, including normal nervous system functioning, and red blood cell development and maturation. It has antioxidant effects, is a co-factor in mitochondrial energy metabolism, and contributes to DNA synthesis, the methylation cycle, and epigenetic regulation. 1 2 B12 is present in foods of animal origin, such as meat, eggs, and milk, or via food fortification. Healthy adults require an average intake of 4-7 mcg daily to maintain B12 status. 3 4 Indications for B12 treatment, administration routes, and preparations Treatment with B12 may be required for a variety of reasons (table 1).</p

From shared care to disease management: key-influencing factors

BACKGROUND: In order to improve the quality of care of chronically ill patients the traditional boundaries between primary and secondary care are questioned. To demolish these boundaries so-called ‘shared care’ projects have been initiated in which different ways of substitution of care are applied. When these projects end, disease management may offer a solution to expand the achieved co-operation between primary and secondary care. OBJECTIVE: Answering the question: What key factors influence the development and implementation of shared care projects from a management perspective and how are they linked? THEORY: The theoretical framework is based on the concept of the learning organisation. DESIGN: Reference point is a multiple case study that finally becomes a single case study. Data are collected by means of triangulation. The studied cases concern two interrelated Dutch shared care projects for type 2 diabetic patients, that in the end proceed as one disease management project. RESULTS: In these cases the predominant key-influencing factors appear to be the project management, commitment and local context, respectively. The factor project management directly links the latter two, albeit managing both appear prerequisites to its success. In practice this implies managing the factors' interdependency by the application of change strategies and tactics in a committed and skilful way. CONCLUSION: Project management, as the most important and active key factor, is advised to cope with the interrelationships of the influencing factors in a gradually more fundamental way by using strategies and tactics that enable learning processes. Then small-scale shared care projects may change into a disease management network at a large scale, which may yield the future blueprint to proceed

Data-driven assessment, contextualisation and implementation of 134 variables in the risk for type 2 diabetes:an analysis of Lifelines, a prospective cohort study in the Netherlands

Aims/hypothesis We aimed to assess and contextualise 134 potential risk variables for the development of type 2 diabetes and to determine their applicability in risk prediction. Methods A total of 96,534 people without baseline diabetes (372,007 person-years) from the Dutch Lifelines cohort were included. We used a risk variable-wide association study (RV-WAS) design to independently screen and replicate risk variables for 5-year incidence of type 2 diabetes. For identified variables, we contextualised HRs, calculated correlations and assessed their robustness and unique contribution in different clinical contexts using bootstrapped and cross-validated lasso regression models. We evaluated the change in risk, or 'HR trajectory', when sequentially assigning variables to a model. Results We identified 63 risk variables, with novel associations for quality-of-life indicators and non-cardiovascular medications (i.e., proton-pump inhibitors, anti-asthmatics). For continuous variables, the increase of 1 SD of HbA(1c), i.e., 3.39 mmol/mol (0.31%), was equivalent in risk to an increase of 0.53 mmol/l of glucose, 19.8 cm of waist circumference, 8.34 kg/m(2) of BMI, 0.67 mmol/l of HDL-cholesterol, and 0.14 mmol/l of uric acid. Other variables required an increase of >3 SD, which is not physiologically realistic or a rare occurrence in the population. Though moderately correlated, the inclusion of four variables satiated prediction models. Invasive variables, except for glucose and HbA(1c), contributed little compared with non-invasive variables. Glucose, HbA(1c) and family history of diabetes explained a unique part of disease risk. Adding risk variables to a satiated model can impact the HRs of variables already in the model. Conclusions Many variables show weak or inconsistent associations with the development of type 2 diabetes, and only a handful can reliably explain disease risk. Newly discovered risk variables will yield little over established factors, and existing prediction models can be simplified. A systematic, data-driven approach to identify risk variables for the prediction of type 2 diabetes is necessary for the practice of precision medicine

Preventive use of nitisinone in alkaptonuria

Abstract Alkaptonuria (AKU, OMIM 203500) is a rare congenital disorder caused by a deficiency of the enzyme homogentisate-1,2,-dioxygenase. The long-term consequences of AKU are joint problems, cardiac valve abnormalities and renal problems. Landmark intervention studies with nitisinone 10 mg daily, suppressing an upstream enzyme activity, demonstrated its beneficial effects in AKU patients with established complications, which usually start to develop in the fourth decade. Lower dose of nitisinone in the range of 0.2–2 mg daily will already reduce urinary homogentisic acid (uHGA) excretion by > 90%, which may prevent AKU-related complications earlier in the course of the disease while limiting the possibility of side-effects related to the increase of plasma tyrosine levels caused by nitisinone. Future preventive studies should establish the lowest possible dose for an individual patient, the best age to start treatment and also collect evidence to which level uHGA excretion should be reduced to prevent complications