Baseline plasma proinsulin response to glucose for predicting therapeutic response to otelixizumab in recent-onset type 1 diabetes.

Aims: In recent-onset type 1 diabetes, clamp-derived C-peptide predicts good response to anti-CD3. Elevated proinsulin and proinsulin/C-peptide ratio (PI/CP) suggest increased metabolic/inflammatory beta cell burden. We reanalyzed trial data to compare the ability of baseline acutely glucose-stimulated proinsulin, C-peptide and PI/CP to predict functional outcome.

Prognostic value of left ventricular global constructive work in patients with cardiac amyloidosis.

Purpose: The aim of the present study was to evaluate the role of ejection fraction (EF), left ventricular (LV) global longitudinal strain (LVGLS) and global constructive work (GCW) as prognostic variables in patients with cardiac amyloidosis (CA).

Methods: CA patients were retrospectively identified between 2015 and 2021 at a tertiary care hospital. Comprehensive clinical, biochemical, and imaging evaluation including two-dimensional (2D) echocardiography with myocardial work (MW) analysis was performed.

Performance of Abbott Alinity hq hematology analyzer for automated cell counting of body fluids.

Introduction: Body fluid cell counting and differentiation provide essential information for diagnosis and monitoring of diverse pathologies. We evaluated the performance of the newly launched Abbott Alinity hq hematology analyzer for automated cell counting in body fluids and compared red blood cell (RBC) and total nucleated cell (TNC) counts with the Cell-Dyn Sapphire automated hematology analyzer. Differential counts were compared with microscopic differentiation on cytocentrifuged preparations.

SLC30A8 polymorphism and BMI complement HLA-A*24 as risk factors for poor graft function in islet allograft recipients.

Aims/hypothesis: HLA-A*24 carriership hampers achievement of insulin independence in islet allograft recipients. However, less than half of those who fail to achieve insulin independence carry the allele. We investigated whether genetic polymorphism at the recipients' zinc transporter 8-encoding SLC30A8 gene (rs13266634) could complement their HLA-A*24 status in predicting functional graft outcome.

Accelerated Progression to Type 1 Diabetes in the Presence of and Is Restricted to Multiple Islet Autoantibody-Positive Individuals With Distinct and Autoantibody Risk Profiles.

Objective: We investigated the effect of HLA class I risk alleles on disease progression in various phases of subclinical islet autoimmunity in first-degree relatives of patients with type 1 diabetes.

Research Design And Methods: A registry-based group of siblings/offspring (aged 0-39 years) was monitored from single- to multiple-autoantibody positivity ( = 267) and from multiple-autoantibody positivity to clinical onset ( = 252) according to , , , and status. Genetic markers were determined by PCR sequence-specific oligotyping.

Twenty-Year Progression Rate to Clinical Onset According to Autoantibody Profile, Age, and Genotype in a Registry-Based Group of Children and Adults With a First-Degree Relative With Type 1 Diabetes.

Objective: We investigated whether islet autoantibody profile, genotype, and age influenced a 20-year progression to diabetes from first autoantibody positivity (autoAb) in first-degree relatives of patients with type 1 diabetes.

Research Design And Methods: Persistently islet autoAb siblings and offspring ( = 462) under 40 years of age were followed by the Belgian Diabetes Registry. AutoAbs against insulin (IAA), GAD (GADA), IA-2 antigen (IA-2A), and zinc transporter 8 (ZnT8A) were determined by radiobinding assay.

Correction: Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio.

[This corrects the article DOI: 10.1371/journal.pone.

Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio.

Background: The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive function tests such as the proinsulin:C-peptide ratio (PI:C). The present study aims to optimize precision of PI:C measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA), and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release.

Methods: Between-day imprecision (n = 20) and split-sample analysis (n = 95) were used to compare TT-TRFIA (AutoDelfia, Perkin-Elmer) with separate methods for proinsulin (in-house TRFIA) and C-peptide (Elecsys, Roche).

HLA-A*24 Carrier Status and Autoantibody Surges Posttransplantation Associate With Poor Functional Outcome in Recipients of an Islet Allograft.

Objective: We investigated whether changes in islet autoantibody profile and presence of HLA risk markers, reported to predict rapid β-cell loss in pre-type 1 diabetes, associate with poor functional outcome in islet allograft recipients.

Research Design And Methods: Forty-one patients received ≥2.3 million β-cells/kg body wt in one to two intraportal implantations.

Relationship between glycaemic variability and hyperglycaemic clamp-derived functional variables in (impending) type 1 diabetes.

Aims/hypothesis: We examined whether measures of glycaemic variability (GV), assessed by continuous glucose monitoring (CGM) and self-monitoring of blood glucose (SMBG), can complement or replace measures of beta cell function and insulin action in detecting the progression of preclinical disease to type 1 diabetes.

Methods: Twenty-two autoantibody-positive (autoAb(+)) first-degree relatives (FDRs) of patients with type 1 diabetes who were themselves at high 5-year risk (50%) for type 1 diabetes underwent CGM, a hyperglycaemic clamp test and OGTT, and were followed for up to 31 months. Clamp variables were used to estimate beta cell function (first-phase [AUC5-10 min] and second-phase [AUC120-150 min] C-peptide release) combined with insulin resistance (glucose disposal rate; M 120-150 min).

Preexisting insulin autoantibodies predict efficacy of otelixizumab in preserving residual β-cell function in recent-onset type 1 diabetes.

Objective: Immune intervention trials in recent-onset type 1 diabetes would benefit from biomarkers associated with good therapeutic response. In the previously reported randomized placebo-controlled anti-CD3 study (otelixizumab; GlaxoSmithKline), we tested the hypothesis that specific diabetes autoantibodies might serve this purpose.

Research Design And Methods: In the included patients (n = 40 otelixizumab, n = 40 placebo), β-cell function was assessed as area under the curve (AUC) C-peptide release during a hyperglycemic glucose clamp at baseline (median duration of insulin treatment: 6 days) and every 6 months until 18 months after randomization.

Hyperglycemic clamp and oral glucose tolerance test for 3-year prediction of clinical onset in persistently autoantibody-positive offspring and siblings of type 1 diabetic patients.

Context And Objective: In preparation of future prevention trials, we aimed to identify predictors of 3-year diabetes onset among oral glucose tolerance test (OGTT)- and hyperglycemic clamp-derived metabolic markers in persistently islet autoantibody positive (autoAb(+)) offspring and siblings of patients with type 1 diabetes (T1D).

Design: The design is a registry-based study.

Setting: Functional tests were performed in a hospital setting.

HLA-A*24 is an independent predictor of 5-year progression to diabetes in autoantibody-positive first-degree relatives of type 1 diabetic patients.

We investigated whether HLA-A*24 typing complements screening for HLA-DQ and for antibodies (Abs) against insulin, GAD, IA-2 (IA-2A), and zinc transporter-8 (ZnT8A) for prediction of rapid progression to type 1 diabetes (T1D). Persistently Ab(+) siblings/offspring (n = 288; aged 0-39 years) of T1D patients were genotyped for HLA-DQA1-DQB1 and HLA-A*24 and monitored for development of diabetes within 5 years of first Ab(+). HLA-A*24 (P = 0.

Evaluation of the multipotent character of human foreskin-derived precursor cells.

In the present study, the trilineage differentiation capacity of human foreskin-derived precursor cells (hSKP) was evaluated upon exposure to various (non)commercial (i and ii) ectodermal, (iii) mesodermal and (iv) endodermal differentiation media. (i) Upon sequential exposure of the cells to keratinocyte growth (CnT-07® or CnT-057®) and differentiation (CnT-02® or Epilife®) media, keratinocyte-like cells (filaggrin(+)/involucrin(+)) were obtained. The preferred keratinocyte differentiation strategy was exposure to CnT-07®.