Changes in markers of hepatic steatosis and fibrosis in patients with type 2 diabetes during treatment with glucagon-like peptide-1 receptor agonists. A multicenter retrospective longitudinal study

AimsMetabolic dysfunction-associated fatty liver disease (MAFLD) is common in people with type 2 diabetes (T2D) and can progress to advanced fibrosis and cirrhosis. In this retrospective study, we explored the longitudinal changes in markers of hepatic steatosis and fibrosis during T2D treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs).MethodsWe analysed observational data from six diabetes outpatient clinics. In the whole T2D population, we calculated the hepatic steatosis index (HSI), which we previously validated against liver ultrasonography, and the Fibrosis (Fib)-4 index. We then identified patients who initiated a GLP-1RA from 2010 to 2018 and for whom data were available to evaluate changes in both HSI and Fib-4 scores over 24 months.ResultsFrom 83,116 outpatients with T2D, 41,302 (49.7%) had complete data for calculating HSI and Fib-4. Most of these T2D patients (∼70%) had MAFLD (defined as HSI>36), 9.7% of whom had advanced fibrosis based on Fib-4 thresholds. Patients with low compared to high risk of advanced fibrosis were 5-times more likely to be treated with GLP-1RA. In 535 patients who initiated a GLP-1RA, the prevalence of MAFLD based on HSI declined significantly at 6 and 24 months, but Fib-4 categories did not. HSI improved significantly only in patients receiving human-based but not exendin-based GLP-1RA, while patients concomitantly receiving metformin had less worsening in Fib-4 categories.ConclusionsMAFLD is very common among outpatients with T2D (∼70%) and the estimated prevalence of advanced fibrosis was ∼10%. Treatment with GLP-1RAs significantly improved MAFLD, but not MAFLD-associated advanced fibrosis.     

Changes in DNA content,number of nuclei and cellular dimensions of young rat atrial myocytes in response to left coronary artery ligation

Studies of enzymatically isolated myocytes from atria of young male Sprague-Dawley rats at 11 days after left coronary artery ligation show that a major response of atrial myocytes to ventricular infarction is binucleation. In sham-operated animals, 23.2% of left and 15.5% of right atrial myocytes were binucleated, compared to 77.8% of left and 40.5% of right atrial myocytes of infarcted animals. Examination of 150 g and 250 g unoperated control animals indicate that this response is occurring at a time when a small but significant amount of binucleation is also occurring as a normal part of growth. Using a Feulgen-acriflavine-SO₂ method for cytofluorometry, a significant increase in ploidy was seen in left atrial myocytes of infarcted animals over those of sham or control animals. The number of left atrial myocytes in infarcted animals having a ploidy level above 3C was 10.8% above sham values. The mean length of binucleated myocytes of left atrium was significantly greater in infarcted animals (119.8 μm) than in sham-operated animals (97 μm) and the mean length of mononucleated myocytes was greater in infarcted animals (104.1 μm) than in sham-operated animals (77 μm). Thus, cardiac myocytes are capable of a substantial response to a stressful situation by increases in cell length, number of nuclei and ploidy. Study of a model system such as the rat atrium may yield an understanding of the mechanisms involved in the induction of these nuclear changes.     

Workplace bullying and violence as risk factors for type 2 diabetes: a multicohort study and meta-analysis

Aims/hypothesis

The aim of this multicohort study was to examine whether employees exposed to social stressors at work, such as workplace bullying and violence, have an increased risk of type 2 diabetes.

Methods

The study included 45,905 men and women (40–65 years of age and free of diabetes at baseline) from four studies in Sweden, Denmark and Finland. Workplace bullying and violence were self-reported at baseline. Incident diabetes was ascertained through national health and medication records and death registers. Marginal structural Cox models adjusted for age, sex, country of birth, marital status and educational level were used for the analyses.

Results

Nine per cent of the population reported being bullied at work and 12% were exposed to workplace violence or threats of violence. Bullied participants had a 1.46 (95% CI 1.23, 1.74) times higher risk of developing diabetes compared with non-bullied participants. Exposure to violence or threats of violence was also associated with a higher risk of diabetes (HR 1.26 [95% CI 1.02, 1.56]). The risk estimates attenuated slightly when taking BMI into account, especially for bullying. The results were similar for men and women, and were consistent across cohorts.

Conclusions/interpretation

We found a higher risk of incident type 2 diabetes among employees exposed to bullying or violence in the workplace. Further research is needed to determine whether policies to reduce bullying and violence at work may reduce the incidence of type 2 diabetes in working populations. Research on the mechanisms is also highly warranted.

     

Association Between Knee Joint Muscle Activation and Knee Joint Moment Patterns During Walking in Moderate Medial Compartment Knee Osteoarthritis: Implications for Secondary Prevention

ObjectiveTo determine associations between knee moment features linked to osteoarthritis (OA) progression, gait muscle activation patterns, and strength.DesignCross-sectional secondary analysis.SettingGait laboratory.ParticipantsConvenience sample of 54 patients with moderate, medial knee OA (N=54).InterventionsNone.Main Outcome MeasuresKnee moments and quadriceps and hamstrings activation were examined during walking. Knee extensor and flexor strength were measured. Waveform patterns were extracted using principal component analysis. Each measured waveform was scored against principal components (PCs) that captured overall magnitude (PC1) and early to midstance difference (PC2) features, with higher PC2 scores interpreted as greater moment differential and more prolonged muscle activity. Correlations were calculated between moment PC scores and muscle PC and strength scores. Regression analyses determined moment PC score variance explained by muscle PC scores and strength.ResultsAll correlations for knee adduction moment difference feature (KAMPC2) and prolonged muscle activity (PC2) were significant (r=−0.40 to −0.54). Knee flexion moment difference feature (KFMPC2) was significantly correlated with all quadriceps and medial hamstrings PC2 scores (r=−0.47 to −0.61) and medial hamstrings magnitude feature (PC1) (r=−0.52). KAMPC2 was significantly correlated with knee flexor strength (r=0.43), and KFMPC2 was significantly correlated with knee extensor (r=0.60) and flexor (r=0.55) strength. Regression models including muscle PC2 scores and knee flexor strength explained 46% of KAMPC2 variance, whereas muscle PC2 scores and knee extensor strength explained 59% of KFMPC2 variance.ConclusionsMuscle activation patterns and strength explained significant variance in moment difference features, highest for the knee flexion moment. This supports that exercises such as neuromuscular training, focused on appropriate muscle activation patterns, and strengthening have the potential to alter dynamic loading gait patterns associated with knee OA clinical progression.     

Current research status of blood biomarkers in Alzheimer’s disease: Diagnosis and prognosis

Alzheimer’s disease (AD), which mainly occurs in the elderly, is a neurodegenerative disease with a hidden onset, which leads to progressive cognitive and behavioral changes. The annually increasing prevalence rate and number of patients with AD exert great pressure on the society. No effective disease-modifying drug treatments are available; thus, there is no cure yet. The disease progression can only be delayed through early detection and drug assistance. Therefore, the importance of exploring associated biomarkers for the early diagnosis and prediction of the disease progress is highlighted. The National Institute on Aging— Alzheimer’s Association (NIA-AA) proposed A/T/N diagnostic criteria in 2018, including Aβ42, p-tau, t-tau in cerebrospinal fluid (CSF), and positron emission tomography (PET). However, the invasiveness of lumbar puncture for CSF assessment and non-popularity of PET have prompted researchers to look for minimally invasive, easy to collect, and cost-effective biomarkers. Therefore, studies have largely focused on some novel molecules in the peripheral blood. This is an emerging research field, facing many obstacles and challenges while achieving some promising results.     

The effect of zirconia and titanium surfaces on biofilm formation and on host-derived immunological parameters

The aim of this study was to analyse the effect of zirconia and titanium surfaces on biofilm formation and host-derived parameters. Studies comparing zirconia and titanium surfaces were selected up to September 1, 2019. The outcome measures were surface roughness, contact angle, bacterial count, bacterial adherence, biofilm thickness, bacterial distribution, and specifically investigated biofilm and specific host-derived immunological parameters. Random-effects meta-analyses of in vitro and in vivo studies were conducted. A total of 39 studies were included for data extraction. In the systematic review data, 10 studies stated that zirconia accumulated less initial oral biofilm parameters, 16 investigations showed negligible inter-material differences, and only one study showed that zirconia attracted the most biofilm. However, in the meta-analysis, the bacterial coverage was found to be significantly superior for zirconia surfaces (P <  0.00001); the other outcome measures did not show any statistically significant differences between zirconia and titanium for the remaining parameters and the studies presented a substantial degree of heterogeneity. Overall, on the basis of the meta-analysis, the current data situation does not allow a clear preference for the use of zirconia or titanium.