Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes

Aims/hypothesis

Better understanding of type 2 diabetes and its prevention is a pressing need. Changes in human plasma N-glycome are associated with many diseases and represent promising diagnostic and prognostic biomarkers. Variations in glucose metabolism directly affect glycosylation through the hexosamine pathway but studies of plasma glycome in type 2 diabetes are scarce. The aim of this study was to determine whether plasma protein N-glycome is changed in individuals who are at greater risk of developing type 2 diabetes.

Methods

Using a chromatographic approach, we analysed N-linked glycans from plasma proteins in two populations comprising individuals with registered hyperglycaemia during critical illness (increased risk for development of type 2 diabetes) and individuals who stayed normoglycaemic during the same condition: AcuteInflammation (59 cases vs 49 controls) and AcuteInflammation Replication (52 cases vs 14 controls) populations. N-glycome was also studied in individuals from FinRisk (37 incident cases of type 2 diabetes collected at baseline vs 37 controls), Orkney Complex Disease Study (ORCADES; 94 individuals with HbA_1c > 6.5% [47.5 mmol/mol] vs 658 controls) and Southall and Brent Revisited (SABRE) cohort studies (307 individuals with HbA_1c > 6.5% [47.5 mmol/mol] vs 307 controls).

Results

Individuals with increased risk for diabetes type 2 development (AcuteInflammation and AcuteInflammation Replication populations), incident cases of type 2 diabetes collected at baseline (FinRisk population) and individuals with elevated HbA_1c (ORCADES and SABRE populations) all presented with increased branching, galactosylation and sialylation of plasma protein N-glycans and these changes were of similar magnitude.

Conclusions/interpretation

Increased complexity of plasma N-glycan structures is associated with higher risk of developing type 2 diabetes and poorer regulation of blood glucose levels. Although further research is needed, this finding could offer a potential new approach for improvement in prevention of diabetes and its complications.

     

Stem Cell Therapy in Patients with Heart Failure

Heart failure results from injury to the myocardium from a variety of causes, including ischemic and nonischemic etiologies. Severe heart failure carries a 50% 5-year mortality rate and is responsible for more than one-third of cardiovascular deaths in the United States.1 Heart failure progression is accompanied by activation of neurohormonal and cytokine systems as well as a series of adaptive changes within the myocardium, collectively referred to as left ventricular remodelling. The unfavorable alterations may be categorized broadly into changes that occur in the cardiac myocytes and changes that occur in the volume and composition of the extracellular matrix.2 Since remodelling in heart failure is progressive and eventually becomes detrimental, the majority of treatment strategies are aimed at stopping or reversing this process. Although medical management, cardiac resychronization therapy, and long-term or destination mechanical circulatory support have been successful in this regard, a considerable number of patients still progress to end-stage heart failure with limited therapeutic options. For these patients, stem cell therapies are being investigated as a safe treatment strategy for decreasing cardiac remodelling on top of conventional medical and device treatment.     

The electronic medical-student exchange: a low-cost alternative to overseas electives.

The authors report on an international collaboration that uses the Internet for medical education. In addition to introducing the students to electronic communication, the project aims to further international collaboration and understanding and to emphasize the importance of a population perspective for health and disease. Students and professors in Canada, England and Hungary participated.     

Data mining and visualization for decision support and modeling of public health-care resources

This paper proposes an innovative use of data mining and visualization techniques for decision support in planning and regional-level management of Slovenian public health-care. Data mining and statistical techniques were used to analyze databases collected by a regional Public Heath Institute. We also studied organizational aspects of public health resources in the selected Celje region with the objective to identify the areas that are atypical in terms of availability and accessibility of public health services for the population. The most important step was the detection of outliers and the analysis of availability and accessibility deviations. The results are applicable to health-care planning and support in decision making by local and regional health-care authorities. In addition to the practical results, which are directly useful for decision making in planning of the regional health-care system, the main methodological contribution of the paper are the developed visualization methods that can be used to facilitate knowledge management and decision making processes.     

Arterial hypertension in Croatia. Results of EH-UH study

Arterial hypertension (AH) is the most important independent risk factor of cardiovascular diseases. The prevalence of AH is higher than it was several decades before, and in Europe it is approximately 40%. A higher prevalence of AH has been reported in Europe than in the United States and Canada. According to the results of epidemiology of arterial hypertension in Croatia study (EH-UH), the prevalence of AH in Croatia is 37.5%. Women are more aware, they were treated more often, and blood pressure control was more frequently achieved than in men. However, body mass index and socioeconomic factors have a greater influence on blood pressure values and prevalence of AH in women. A low level of health education and inappropriate treatment are the most important reasons for the poor blood pressure control observed. Measures of primary prevention should be performed continuously and adjusted to special population subgroups. As an increase of obesity and hypertension was observed in school children, these measures should start at that age.     

Adult metachromatic leukodystrophy: a new mutation in the schizophrenia-like phenotype with early neurological signs

OBJECTIVES: The adult type of metachromatic leukodystrophy can manifest itself as motor or as psycho-cognitive form, the latter is very similar to schizophrenia. We report on two sisters with adult metachromatic leukodystrophy who display symptoms of both forms. METHODS: Presented are genotype analyses and 4-year follow-up data regarding clinical manifestations as well as neurocognitive and neuroimaging results for two adult sisters with metachromatic leukodystrophy. RESULTS: Whereas the younger sister developed disorganized schizophrenia-like symptoms, the other exhibited schizophrenia-like, negative symptoms. In both sisters, neurological signs were already present at the onset of the disease and progression towards dementia was documented within 1-2 years. In peripheral leukocytes, the activity of arylsulphatase A was reduced to 2 and 5% of the mean normal activity in both women. Genotype analysis revealed compound heterozygosity for a known severe splice site mutation, (c.459+1G>A) together with two known polymorphisms, [(c.937G>T), (p.Trp193Asp)] and [(c.1530C>G), (p.Thr391Ser)], and a novel missense mutation, (c.1194C>T). The latter results in the exchange of a conserved polar amino acid, threonine 279, to hydrophobic isoleucine (Thr279Ileu), which could not be found among >100 control alleles. A family analysis identified T279I as the paternal allele, whereas (c.459+1G>A) as well as the two polymorphisms were inherited from the mother. This is consistent with a disease-causing effect of the novel mutation. CONCLUSIONS: The novel mutation, T279I detected in our patients, correlates with a specific phenotype with schizophrenia-like symptoms, neurological signs and cognitive impairment early in the course of the disease and a relatively fast progression towards dementia. This is in contrast to previous reports on adult metachromatic leukodystrophy patients with the psycho-cognitive phenotype who did not show any neurological signs for decades, however, most of these patients were heterozygous for another specific missense mutation, I179S.     

Chronic Dietary Exposure to Aristolochic Acid and Kidney Function in Native Farmers from a Croatian Endemic Area and Bosnian Immigrants

Background and objectives

Improvements in agricultural practices in Croatia have reduced exposure to consumption of aristolochic acid-contaminated flour and development of endemic (Balkan) nephropathy. Therefore, it was hypothesized that Bosnian immigrants who settled in an endemic area in Croatia 15–30 years ago would be at lower risk of developing endemic nephropathy because of reduced exposure to aristolochic acid. To test this hypothesis, past and present exposure to aristolochic acid, proximal tubule damage as a hallmark of endemic nephropathy, and prevalence of CKD in Bosnian immigrants were analyzed.

Design, setting, participants, & measurements

In this cross-sectional observational study from 2005 to 2010, 2161 farmers were divided into groups: indigenous inhabitants from endemic nephropathy and nonendemic nephropathy villages and Bosnian immigrants; α-1 microglobulin-to-creatinine ratio >31.5 mg/g and eGFR<60 ml/min per 1.73 m² were considered to be abnormal.

Results

CKD and proximal tubule damage prevalence was significantly lower in Bosnian immigrants than inhabitants of endemic nephropathy villages (6.9% versus 16.6%; P<0.001; 1.3% versus 7.3%; P=0.003, respectively); 20 years ago, Bosnian immigrants observed fewer Aristolochia clematitis in cultivated fields (41.9% versus 67.8%) and fewer seeds among wheat seeds (6.1% versus 35.6%) and ate more purchased than homemade bread compared with Croatian farmers from endemic nephropathy villages (38.5% versus 14.8%, P<0.001). Both Croatian farmers and Bosnian immigrants observe significantly fewer Aristolochia plants growing in their fields compared with 15–30 years ago. Prior aristolochic acid exposure was associated with proximal tubule damage (odds ratio, 1.64; 95% confidence interval, 1.04 to 2.58; P=0.02), whereas present exposure was not (odds ratio, 1.31; 95% confidence interval, 0.75 to 2.30; P=0.33). Furthermore, immigrant status was an independent negative predictor of proximal tubule damage (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.86; P=0.02).

Conclusions

Bosnian immigrants and autochthonous Croats residing in endemic areas are exposed significantly less to ingestion of aristolochic acid than in the past. The prevalence of endemic nephropathy and its associated urothelial cancers is predicted to decrease over time.     

Scapular Notching on Kinematic Simulated Range of Motion After Reverse Shoulder Arthroplasty Is Not the Result of Impingement in Adduction

Impingement after reverse shoulder arthroplasty (RSA) is believed to occur from repetitive contact in adduction between the humeral component and the inferior scapular pillar. The primary purpose of this biomechanical study was to confirm the presence of different types of impingement and to examine which daily-life movements are responsible for them. A secondary aim was to provide recommendations on the type of components that would best minimize notching and loss of range of motion (ROM).The study included 12 fresh frozen shoulder specimens; each had a computed tomography (CT) image of the entire scapula and humerus in order to acquire topological information of the bones before RSA implantation. Cyclic tests were run postimplantation with 3 shoulders in each modalities. To quantify bone loss due to impingement, 3-dimensional anatomical models of the scapula were reconstructed from the CT scans and compared to their intact states.We found 8 bony impingements in 7 specimens: 2 at the lateral acromion, 1 at the inferior acromion, 4 scapular notching, and 1 with the glenoid resulting to wear at the 3:00 to 6:00 clock-face position. Impingements occurred in all kinds of tested motions, except for the internal/external rotation at 90° of abduction. The 3 specimens tested in abduction/adduction presented bone loss on the acromion side only. Scapular notching was noted in flexion/extension and in internal/external rotation at 0° of abduction. The humeral polyethylene liner was worn in 2 specimens—1 at the 6:00 to 8:00 clock-face position during internal/external rotation at 0° of abduction and 1 at the 4:00 clock-face position during flexion/extension.The present study revealed that 2 types of impingement interactions coexist and correspond to a frank abutment or lead to a scapular notching (friction-type impingement). Scapular notching seems to be caused by more movements or combination of movements than previously considered, and in particular by movements of flexion/extension and internal/external rotation with the arm at the side. Polyethylene cups with a notch between 3 and 9 o’clock and lower neck-shaft angle (145° or 135°) may play an important role in postoperative ROM limiting scapular notching.