👤 Tonia de Las Heras Gala

Conflicting results have been reported regarding the effect of word predictability when reading with eccentric vision. The present study aims to shed light on these discrepancies by investigating how in-context word predictability influences reading performance with a simulated scotoma, while considering the visual and lexical features of words. Thirty-five healthy young people read aloud sentences presented using the self-paced reading paradigm. A group of 22 participants practiced reading with a 10° diameter, gaze-contingent simulated central scotoma, with the other group serving as controls. Each participant underwent two in-lab sessions, reading 304 sentences (2-4 hours, depending on their group). Reading time, fixation number, and duration were analyzed for each target word using mixed-effect models. When reading with a simulated scotoma, in-context predictability shows a significant effect on performance, with a 35% decrease in reading time for highly predictable words compared with unpredictable ones (2.5 seconds vs. 1.6 seconds). This effect is modulated by practice, with the decrease dropping to 22% (1.3 seconds vs. 1.0 seconds) after only few hours of scotoma exposure. This effect seems to be driven by the total number of fixations required to identify words and is absent in the control group. These results support the hypothesis that reading with eccentric vision, which limits visual access to text, results in a stronger in-context predictability advantage. Moreover, this effect has a greater impact early in eccentric reading practice. This suggests greater reliance on linguistic inferences to compensate for impaired visual input, compared with central reading, at least until functional adaptation occurs. Show less

Hypertriglyceridemia is characterized by elevated triglyceride levels in the blood, which increases the risk of cardiovascular disease and pancreatitis. This condition stems from multiple factors including lifestyle choices, genetics, and conditions such as diabetes and metabolic syndrome. Apolipoprotein C-III (APOC3), a protein for lipid metabolism, hinders enzymes necessary for breaking down triglycerides and thus plays a key role in hypertriglyceridemia. Variations in the APOC3 gene are associated with varying triglyceride levels among individuals. Recent genetic studies and clinical trials have shed light on the potential of targeting APOC3 as a potentially promising therapeutic modality of hypertriglyceridemia. Antisense oligonucleotides like volanesorsen have displayed effectiveness in lowering triglyceride levels in individuals with severe hypertriglyceridemia. This review article delves into how APOC3 influences triglyceride control and its potential use in targeting APOC3 to manage severe hypertriglyceridemia. Show less

The objective of the present study was to identify proteins that contribute to pathophysiology and allow prediction of incident type 2 diabetes or incident prediabetes. We quantified 14 candidate proteins using targeted mass spectrometry in plasma samples of the prospective, population-based German KORA F4/FF4 study (6.5-year follow-up). 892 participants aged 42-81 years were selected using a case-cohort design, including 123 persons with incident type 2 diabetes and 255 persons with incident WHO-defined prediabetes. Prospective associations between protein levels and diabetes, prediabetes as well as continuous fasting and 2 h glucose, fasting insulin and insulin resistance were investigated using regression models adjusted for established risk factors. The best predictive panel of proteins on top of a non-invasive risk factor model or on top of HbA1c, age, and sex was selected. Mannan-binding lectin serine peptidase (MASP) levels were positively associated with both incident type 2 diabetes and prediabetes. Adiponectin was inversely associated with incident type 2 diabetes. MASP, adiponectin, apolipoprotein A-IV, apolipoprotein C-II, C-reactive protein, and glycosylphosphatidylinositol specific phospholipase D1 were associated with individual continuous outcomes. The combination of MASP, apolipoprotein E (apoE) and adiponectin improved diabetes prediction on top of both reference models, while prediabetes prediction was improved by MASP plus CRP on top of the HbA1c model. In conclusion, our mass spectrometric approach revealed a novel association of MASP with incident type 2 diabetes and incident prediabetes. In combination, MASP, adiponectin and apoE improved type 2 diabetes prediction beyond non-invasive risk factors or HbA1c, age and sex. Show less

Gliptins act by increasing endogenous incretin levels. Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic peptide receptor (GIPR) are their indirect drug targets. Variants of GLP1R and GIPR have previously been associated with the incretin effect. The aim of the present pilot study was to examine associations of the GLP1R and GIPR gene variants with the glycaemic response to gliptins. A total of 140 consecutive patients with type 2 diabetes were followed-up 6 months after initiation of gliptin treatment. GLP1R rs6923761 (Gly168Ser) and GIPR rs10423928 genotyping was performed using real-time PCR, with subsequent high-resolution melting analysis. The main study outcome was reduction in glycated haemoglobin (HbA1c) after treatment. GLP1R Gly168Ser variant was significantly associated with reduction in HbA1c in an additive model (β = -0.33, p = 0.011). The mean reduction in HbA1c in Ser/Ser homozygotes was significantly lower compared with Gly-allele carriers [0.12 ± 0.23% vs. 0.80 ± 0.09% (1.3 ± 2.5 mmol/mol vs. 8.7 ± 1.0 mmol/mol); p = 0.008]. In conclusion, GLP1R missense variant was associated with a reduced response to gliptin treatment. The genotype-related effect size of ∼0.7% (8 mmol/mol) is equal to an average effect of gliptin treatment and makes this variant a candidate for use in precision medicine. Show less

Maternal obesity is a worldwide problem associated with increased risk of metabolic diseases in the offspring. Genetic deletion of the gastric inhibitory polypeptide (GIP) receptor (GIPR) prevents high-fat diet (HFD)-induced obesity in mice due to specific changes in energy and fat cell metabolism. We investigated whether GIP-associated pathways may be targeted by fetal programming and mimicked the situation by exposing pregnant mice to control or HFD during pregnancy (intrauterine [IU]) and lactation (L). Male wild-type (WT) and Gipr(-/-) offspring received control chow until 25 weeks of age followed by 20 weeks of HFD. Gipr(-/-) offspring of mice exposed to HFD during IU/L became insulin resistant and obese and exhibited increased adipose tissue inflammation and decreased peripheral tissue substrate utilization after being reintroduced to HFD, similar to WT mice on regular chow during IU/L. They showed decreased hypothalamic insulin sensitivity compared with Gipr(-/-) mice on control diet during IU/L. DNA methylation analysis revealed increased methylation of CpG dinucleotides and differential transcription factor binding of promoter regions of genes involved in lipid oxidation in the muscle of Gipr(-/-) offspring on HFD during IU/L, which were inversely correlated with gene expression levels. Our data identify GIP-regulated metabolic pathways that are targeted by fetal programming. Show less

Individuals at a high risk of type 2 diabetes demonstrate moderate impairments in glucose metabolism years before the clinical manifestation of type 2 diabetes, a state called 'prediabetes'. In order to elucidate the pathophysiological processes leading to type 2 diabetes, we aimed to identify protein biomarkers associated with prediabetes. In a proteomics study, we used targeted selected reaction monitoring (SRM)-MS to quantify 23 candidate proteins in the plasma of 439 randomly selected men and women aged 47-76 years from the population-based German KORA F4 study. Cross-sectional associations of protein levels with prediabetes (impaired fasting glucose and/or impaired glucose tolerance), type 2 diabetes, glucose levels in both the fasting state and 2 h after an OGTT, fasting insulin and insulin resistance were investigated using regression models adjusted for technical covariables, age, sex, BMI, smoking, alcohol intake, physical inactivity, actual hypertension, triacylglycerol levels, total cholesterol/HDL-cholesterol ratio, and high-sensitivity C-reactive protein levels. Mannan-binding lectin serine peptidase 1 (MASP1; OR per SD 1.77 [95% CI 1.26, 2.47]), thrombospondin 1 (THBS1; OR per SD 1.55 [95% CI 1.16, 2.07]) and glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1; OR per SD 1.40 [95% CI 1.01, 1.94]) were positively associated with prediabetes, and apolipoprotein A-IV (ApoA-IV; OR per SD 0.75 [95% CI 0.56, 1.00]) was inversely associated with prediabetes. MASP1 was positively associated with fasting and 2 h glucose levels. ApoA-IV was inversely and THBS1 was positively associated with 2 h glucose levels. MASP1 associations with prediabetes and fasting glucose resisted Bonferroni correction. Type 2 diabetes associations were partly influenced by glucose-lowering medication. We discovered novel and independent associations of prediabetes and related traits with MASP1, and some evidence for associations with THBS1, GPLD1 and ApoA-IV, suggesting a role for these proteins in the pathophysiology of type 2 diabetes. Show less