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ed before recommended routine screening period reflects early pathophysiological derangements in beta-cell function and glucose disposal that are characteristic of GDM development and may be useful in early risk stratification.

Intensification of therapy has been associated with early worsening of retinopathy prior to subsequent risk reduction. We sought to assess whether glycated hemoglobin (HbA1c) reduction, following flash monitoring, was associated with early worsening.

An observational study in 541 individuals with type 1 diabetes and paired HbA1c and eye assessment prior to and following flash monitoring commencement.

Change in HbA1c was -4 mmol/mol (IQR -9-1) (-0.4% (-0.8-0.1)) and 25% achieved a fall in HbA1c of ≥10 mmol/mol. The occurrence of the composite end point (panretinal photocoagulation, macular laser or anti-VEGF therapy) was associated with baseline HbA1c >75 mmol/mol (9.0%) (HR 4.0 (95% CI 2.0 to 7.9), p<0.001) but not with fall in HbA1c of ≥10 mmol/mol (0.9%) (HR 1.6 (95% CI 0.8 to 3.2), p=0.203) over a follow-up period of 615 days (527-863). In multivariate analysis, diabetes duration (p=0.035) and prior retinopathy (p<0.001) were most predictive of the composite end point. Baseline HbA1c was the strongest predictor of worsening retinopathy (p=0.002) or new retinopathy (p=0.002) in multivariate analysis whereas change in HbA1c was not independently associated with either (p=0.930 and p=0.830, respectively).

Progression of eye disease is associated with baseline HbA1c, diabetes duration and previous retinopathy and such individuals should be monitored during intensification of glycemic therapy. Reassuringly, the extent of glucose lowering does not appear to be an independent risk factor for early worsening of eye disease in this context.

Progression of eye disease is associated with baseline HbA1c, diabetes duration and previous retinopathy and such individuals should be monitored during intensification of glycemic therapy. Reassuringly, the extent of glucose lowering does not appear to be an independent risk factor for early worsening of eye disease in this context.

The insulinotropic capacity of exogenous glucagon like peptide-1 (GLP-1) is reduced in type 2 diabetes and the insulin-resistant obese. We have tested the hypothesis that this response is the consequence of a reduced pancreatic GLP-1 receptor (GLP-1r) density in insulin-resistant obese animals.

GLP-1r density was measured in lean and insulin-resistant adult miniature pigs after the administration of a

Ga-labeled GLP-1r agonist. The effect of hyperinsulinemia on GLP-1r was assessed using sequential positron emission tomography (PET), both in the fasted state and during a clamp. The impact of tissue perfusion, which could account for changes in GLP-1r agonist uptake, was also investigated using

Ga-DOTA imaging.

GLP-1r binding potential in the obese pancreas was reduced by 75% compared with lean animals. Similar reductions were evident for fat tissue, but not for the duodenum. In the lean group, induced hyperinsulinemia reduced pancreatic GLP-1r density to a level comparable with that of the obese group. The reduction in blood to tissue transfer of the GLP-1r ligand paralleled that of tissue perfusion estimated using

Ga-DOTA.

These observations establish that a reduction in abdominal tissue perfusion and a lower GLP-1r density account for the diminished insulinotropic effect of GLP-1 agonists in type 2 diabetes.

These observations establish that a reduction in abdominal tissue perfusion and a lower GLP-1r density account for the diminished insulinotropic effect of GLP-1 agonists in type 2 diabetes.

Patients with the ultra-rare Wolfram syndrome (WFS) develop insulin-dependent diabetes and progressive neurodegeneration. The aim of the study was to quantify microRNAs (miRNAs) in sera from patients with WFS, correlate their expression with neurological imaging over time and compare miRNA levels with those observed in patients with type 1 diabetes mellitus (T1DM).

We quantified miRNA expression (Qiagen, Germany) in two groups of patients with WFS at study entry (n=14) and after 2 years of follow-up and in 15 glycated hemoglobin-matched (p=0.72) patients with T1DM.

We observed dynamic changes in the expression of multiple miRNAs in patients with WFS parallel to disease progression and in comparison to the T1DM patients group. Among miRNAs that differed between baseline and follow-up WFS samples, the level of 5 increased over time (miR-375, miR-30d-5p, miR-30e-30, miR-145-5p and miR-193a-5p) and was inversely correlated with macular average thickness, while the expression of 2 (let-7g-5p and miR-22-3p) decreased and was directly correlated with neuroimaging indicators of neurodegeneration.

Our findings show for the first time that serum miRNAs can be used as easily accessible indicators of disease progression in patients with WFS, potentially facilitating clinical trials on mitigating neurodegeneration.

Our findings show for the first time that serum miRNAs can be used as easily accessible indicators of disease progression in patients with WFS, potentially facilitating clinical trials on mitigating neurodegeneration.

The aim of this study was to investigate the impact of acute left ventricular unloading by percutaneous left ventricular assist device on pulmonary congestion and pneumonia in patients with cardiogenic shock (CS).

In this retrospective study, we analysed patients with CS who received the Impella percutaneous left ventricular assist device (n=50) compared with those who received intra-aortic balloon pump (IABP) support (n=50). Pulmonary congestion was longitudinally assessed while on support by calculating characteristic findings on the chest X-ray using the Halperin score. GDC-0068 The rate of pneumonia and early mortality were assessed as a secondary endpoint.

The groups (Impella vs IABP) did not differ in terms of age, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology, Chronic Health Evaluation (APACHE) II score or serum lactate levels. Pulmonary congestion decreased in patient treated with Impella at each time point postimplantation. No change in congestion status was observed in patients supported with IABP.