Is Afamin a novel biomarker for gestational diabetes mellitus? A pilot study

Abstract Background In search of potential early biomarkers for timely prediction of gestational diabetes mellitus (GDM), we focused on afamin, a vitamin E–binding protein in human plasma.. Afamin plays a role in anti-apoptotic cellular processes related to oxidative stress and is associated with insulin resistance and other features of metabolic syndrome. During uncomplicated pregnancy its serum concentrations increase linearly. The aim of this study was to investigate the suitability of afamin as early marker for predicting GDM. Methods In a first-trimester cohort from a prospective observational study of adverse pregnancy outcomes we secondarily analyzed afamin concentrations in 59 patients diagnosed with GDM and 51 controls. Additionally, afamin concentrations were cross-sectionally examined in a mid-trimester cohort of 105 women and compared with results from a simultaneously performed oral glucose tolerance test (OGTT). Subgroup analysis comparing patients treated with either insulin (iGDM) or dietary intervention (dGDM) was performed in both cohorts. Patients were recruited at the University Hospital Essen, Germany, between 2003 and 2016. Results Results were adjusted for body-mass-index (BMI) and gestational age. First and mid-trimester cohorts yielded significantly elevated afamin concentrations in patients with pathological OGTT compared to patients without GDM (first trimester cohort: mean, 113.4 mg/l; 95% CI, 106.4–120.5 mg/l and 87.2 mg/l; 95% CI, 79.7–94.7 mg/l; mid-trimester cohort: mean, 182.9 mg/l; 95% CI, 169.6–196.2 mg/l and 157.3 mg/l; 95% CI, 149.1–165.4 mg/l, respectively). In the first-trimester cohort, patients developing iGDM later in pregnancy presented with significantly higher afamin concentrations compared to patients developing dGDM and compared to patients without GDM. In the mid-trimester cohort, mean concentrations of afamin differed significantly between patients with dGDM compared to controls and between patients with iGDM and controls. Patients with iGDM showed only slightly higher afamin levels compared to patients with dGDM. Conclusion Afamin may serve as a new early biomarker for pathological glucose metabolism during pregnancy. Further research is needed to determine afamin’s concentrations during pregnancy, its predictive value for early detection of pregnancies at high risk to develop GDM and its diagnostic role during the second trimester

Table_1_Effects of medication intake on the risk of hemorrhage in patients with sporadic cerebral cavernous malformations.docx

ObjectiveRecurrent intracerebral hemorrhage (ICH) poses a high risk for patients with cerebral cavernous malformations (CCMs). This study aimed to assess the influence of medication intake on hemorrhage risk in sporadic CCMs.MethodsFrom a database of 1,409 consecutive patients with CCM (2003–2021), subjects with sporadic CCMs and complete magnetic resonance imaging data were included. We evaluated the presence of ICH as a mode of presentation, the occurrence of ICH during follow-up, and medication intake, including beta blockers, statins, antithrombotic therapy, and thyroid hormones. The impact of medication intake on ICH at presentation was calculated using univariate and multivariate logistic regression with age and sex adjustment. The longitudinal cumulative 5-year risk for (re-)hemorrhage was analyzed using the Kaplan–Meier curves and the Cox regression analysis.ResultsA total of 1116 patients with CCM were included. Logistic regression analysis showed a significant correlation (OR: 0.520, 95% CI: 0.284–0.951, p = 0.034) between antithrombotic therapy and ICH as a mode of presentation. Cox regression analysis revealed no significant correlation between medication intake and occurrence of (re-)hemorrhage (hazard ratios: betablockers 1.270 [95% CI: 0.703–2.293], statins 0.543 [95% CI: 0.194–1.526], antithrombotic therapy 0.507 [95% CI: 0.182–1.410], and thyroid hormones 0.834 [95% CI: 0.378–1.839]).ConclusionIn this observational study, antithrombotic treatment was associated with the tendency to a lower rate of ICH as a mode of presentation in a large cohort of patients with sporadic CCM. Intake of beta blockers, statins, and thyroid hormones had no effect on hemorrhage as a mode of presentation. During the 5-year follow-up period, none of the drugs affected the further risk of (re-)hemorrhage.</p

SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe

Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe. Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe