A subclass of serum anti-ZnT8 antibodies directed to the surface of live pancreatic β-cells.

The islet-specific zinc transporter ZnT8 is a major self-antigen found in insulin granules of pancreatic β-cells. Frequent insulin secretion exposes ZnT8 to the cell surface, but the humoral antigenicity of the surface-displayed ZnT8 remains unknown. Here we show that a membrane-embedded human ZnT8 antigen triggered a vigorous immune response in knock-out mice.

Fluctuation localization imaging-based fluorescence in situ hybridization (fliFISH) for accurate detection and counting of RNA copies in single cells.

Quantitative gene expression analysis in intact single cells can be achieved using single molecule-based fluorescence in situ hybridization (smFISH). This approach relies on fluorescence intensity to distinguish between true signals, emitted from an RNA copy hybridized with multiple oligonucleotide probes, and background noise. Thus, the precision in smFISH is often compromised by partial or nonspecific probe binding and tissue autofluorescence, especially when only a small number of probes can be fitted to the target transcript.

Change in hemoglobin A1c one year following the 2014 American Diabetes Association guideline update.

Aims: In June 2014, the American Diabetes Association lowered recommended hemoglobin A1c (HbA1c) targets from <8.5% (69mmol/mol) for children <6years of age and from <8.0% (64mmol/mol) for children 6-12years of age to <7.

A survey of youth with new onset type 1 diabetes: Opportunities to reduce diabetic ketoacidosis.

Objective: Pediatric patients in Colorado with new onset type 1 diabetes (T1D) presenting with diabetic ketoacidosis (DKA) increased from 29.9% to 46.2% from 1998 to 2012.

Predominance of DR3 in Somali children with type 1 diabetes in the twin cities, Minnesota.

Background: Minnesota is home to the largest Somali population in USA, and pediatric diabetes teams are seeing increasing numbers of Somali children with diabetes.

Objective: To assess the immune basis of diabetes in Somali children in the Twin Cities, Minnesota.

Methods: A total of 31 Somali children ≤19 yr were treated for type 1 diabetes (T1D) at the University of Minnesota Masonic Children's Hospital and Children's Hospitals and Clinics of Minnesota underwent analysis of human leukocyte antigen (HLA) alleles (n = 30) and diabetes autoantibodies [glutamic acid decarboxylase (GAD65), islet antigen 2 (IA-2), zinc transporter 8 (ZnT8); n = 31].

Low Level Pro-inflammatory Cytokines Decrease Connexin36 Gap Junction Coupling in Mouse and Human Islets through Nitric Oxide-mediated Protein Kinase Cδ.

Pro-inflammatory cytokines contribute to the decline in islet function during the development of diabetes. Cytokines can disrupt insulin secretion and calcium dynamics; however, the mechanisms underlying this are poorly understood. Connexin36 gap junctions coordinate glucose-induced calcium oscillations and pulsatile insulin secretion across the islet.

Updates in behavioural and psychosocial literature in adolescents with type 1 diabetes.

Purpose Of Review: Adolescence is a well known, high-risk time period for all youth, and in patients with type 1 diabetes, glycemic control is at its worst. This manuscript will review updates in adolescent diabetes literature between February 2014 and February 2015. The article will highlight new research in the behavioural and psychosocial literature focused on type 1 diabetes in adolescents, including compliance with standards of care, quality of life, depression, psychological burden of type 1 diabetes, parental involvement, the parent-child relationship, self-management, socioeconomic status and transition and transfer of care.

Beta-cell regeneration in human pancreas: the lessons of pancreatic pathology.

Diabetes mellitus has been traditionally classified as Type 1 and Type 2 on the basis of several criteria that generally reflect either insulin deficiency or functional defects in insulin secretion. In this chapter, we propose a new classification diabetes based on age of onset, body mass index and biomarkers such as islet autoantibodies and DR HLA alleles. In the second part of this chapter, we briefly discuss some novel hypotheses on the possibility of beta-cell regeneration in diabetes in relation to the islet pathology of the disease.

Effectiveness of an informational video method to improve enrollment and retention of a pediatric cohort.

Objective: The Environmental Determinants of Diabetes in the Young (TEDDY), a multinational epidemiological study, is designed to identify environmental exposures triggering autoimmunity and type 1 diabetes (T1D) in children at increased genetic risk. The objective of this analysis was to evaluate the use of an informational video in the enrollment and retention of eligible participants at the Colorado TEDDY clinical center.

Study Design And Setting: Eligible participants were divided into two groups based on the inclusion of the video in the enrollment materials: the No-Video Group (n=449) did not receive the video and were contacted between 7/1/07 and 6/30/08.

Wolfram Syndrome: a rare optic neuropathy in youth with type 1 diabetes.

Wolfram Syndrome (WS) is a rare, autosomal recessive disorder that causes non-autoimmune type 1 diabetes. The etiology involves a single gene mutation of the wolframin protein inducing endoplasmic reticulum stress and apoptosis in selected cell types with resultant diabetes insipidus, diabetes mellitus, optic atrophy, and sensory-neural deafness. Symptoms are initially absent and signs within the posterior segment of the eye are usually the earliest indicator of WS.

The past, present, and future of genetic associations in type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease affecting approximately one in 300 individuals in the United States. The majority of genetic research to date has focused on the heritability that predisposes to islet autoimmunity and T1DM. The evidence so far points to T1DM being a polygenic, common, complex disease with major susceptibility lying in the major histocompatibility complex (MHC) on chromosome 6 with other smaller effects seen in loci outside of the MHC.

Lipoprotein-associated phospholipase A₂ activity predicts progression of subclinical coronary atherosclerosis.

Background: Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a lipoprotein-associated enzyme that cleaves oxidized phosphatidylcholines, generating pro-atherosclerotic lysophosphatidylcholine and oxidized free fatty acids. Lp-PLA₂ is independently associated with cardiovascular disease (CVD) in a variety of populations. Coronary calcium is a measure of subclinical CVD, and progression of coronary calcification predicts future CVD events.

Beta cell regeneration in human pancreas.

The issue of beta cell regeneration in human pancreas is probably one of the most controversial aspects of type 1 diabetes research. In this review, we will first describe the known mechanisms underlying beta cell development and expansion in normal human pancreatic development because it is likely that such mechanisms might also play a role in beta cell regeneration. The sensu strictiori definition of beta cells implies replacement of lost beta cell mass by new beta cells.

Prevention strategies for type 1 diabetes.

Type 1 diabetes (T1D) is a common chronic disease of childhood. Patients with T1D are at significant risk for developing serious health complications. Understanding of the genetics, environmental factors, and natural history of diabetes has lead to greater understanding of the etiology and epidemiology of T1D.

Clinical review: Type 1 diabetes-associated autoimmunity: natural history, genetic associations, and screening.

Context: Type 1 diabetes (T1D) is associated with autoimmune thyroid disease (AIT), celiac disease (CD), Addison's disease (AD), and other autoimmune diseases. These diseases can occur together in defined syndromes with distinct pathophysiology and characteristics: autoimmune polyendocrine syndrome I, autoimmune polyendocrine syndrome II, and the immunodysregulation polyendocrinopathy enteropathy X-linked syndrome.

Evidence Acquisition: Review of the medical literature was performed with particular attention to the natural history, genetic factors, and syndromes associated with T1D, AIT, CD, and AD.

Increased incidence and severity of diabetic ketoacidosis among uninsured children with newly diagnosed type 1 diabetes mellitus.

Objectives: (a) To determine the incidence and severity of diabetic ketoacidosis (DKA) and (b) to stratify according to insurance status at the initial diagnosis of type 1 diabetes (T1DM).

Research Design And Methods: Subjects included children <18 yr who presented with new-onset T1DM from January 2002 to December 2003 and were subsequently followed at the Barbara Davis Center. Insurance status and initial venous pH were obtained.

Real-time glucose sensing using transdermal fluid under continuous vacuum pressure in children with type 1 diabetes.

Background: This study was designed to evaluate the accuracy and tolerance in children of an experimental device for continuous glucose monitoring. This real-time glucose sensing (RTGS) system measures transdermal fluid glucose through micropores in the stratum corneum that are kept open by continuous vacuum pressure.

Design And Methods: A comparison of self-monitored blood glucose values and RTGS values was obtained in 110 children with type 1 diabetes ranging in age from 2 to 18 years.

The stages of type 1A diabetes: 2005.

Type 1A diabetes is a chronic autoimmune disease usually preceded by a long prodrome during which autoantibodies to islet autoantigens are present. These antibodies are directed to a variety of antigens, but the best characterized are glutamic acid decarboxylase-65, insulinoma-associated antigen-2, and insulin. We hypothesize that the natural history of type 1A diabetes can be represented by several stages, starting from genetic susceptibility and ending in complete beta-cell destruction and overt diabetes.

Elevated C-reactive protein levels in the development of type 1 diabetes.

Elevated C-reactive protein (CRP) levels have previously been described before the onset of type 2 diabetes and gestational diabetes. We hypothesized that inflammation, as reflected by elevated CRP levels, can help predict development of islet autoimmunity or type 1 diabetes. Children at risk for type 1 diabetes and followed in the Diabetes Autoimmunity Study of the Young (DAISY) had blood samples drawn and frozen serum saved at various intervals after birth.

A major role for host MHC class I antigen presentation for promoting islet allograft survival.

The purpose of this study was to determine the role for CD8 T cells versus generalized MHC class I-restricted antigen presentation in islet allograft rejection and tolerance. Diabetic C57BI/6 (B6, H-2(b)) controls, C57BI/6 CD8-deficient (CD8 KO), or MHC class I-deficient C57BI/6 (beta 2m KO) recipients were grafted with allogeneic BALB/c (H-2(d)) islets. Islet allografts were acutely rejected in untreated B6, CD8 KO, and in beta 2m KO mice, indicating that neither CD8 T cells nor host MHC class I is required for allograft rejection.

Distinct requirements for host CD80/CD86 costimulatory molecules in cardiac versus islet rejection.

The role of B7 family members CD80 and CD86 in providing costimulatory signals to T cells is well established. Interestingly, previous studies show that host CD80/CD86 expression is required for cardiac allograft rejection. However, the role for host costimulation by CD80/CD86 molecules for the rejection of neovascularized islet allografts and xenografts is unknown.

Life with continuous subcutaneous insulin infusion (CSII) therapy: child and parental perspectives and predictors of metabolic control.

Objective: The purpose of this study was twofold (i): to evaluate metabolic control in patients receiving CSII therapy in a routine pediatric diabetes clinic by describing reasons for initiating therapy and daily management issues, including needle fear; and (ii) to assess the change in parental involvement and anxiety once their child initiated CSII therapy.

Research Design And Methods: The study included 52 subjects (aged 7.6-23.

Rapid assays for detection of anti-islet autoantibodies: implications for organ donor screening.

The purpose of the current study was to develop and evaluate rapid assays for autoantibodies to GAD65 (GAA), ICA512bdc/IA-2 (ICA512AA), and insulin (microIAA, mIAA) as a potential tool for identification of cadaveric pancreas donors who were at high risk for developing diabetes. The study included 154 new onset diabetic, prediabetic, and healthy control subjects. Subjects were evaluated for all three autoantibodies in three separate assays: (1) standard (std) assay with a 24-h or 72-h incubation at 4 degrees C (combined GAA/ICA512AA or mIAA, respectively), (2) rapid assay with 1-h room temperature (RT) incubation, and (3) rapid assay with 2-h RT incubation.