Herpes Simplex Virus 1 Infection of Human Brain Organoids and Pancreatic Stem Cell-Islets Drives Organoid-Specific Transcripts Associated with Alzheimer's Disease and Autoimmune Diseases.

Viral infections leading to inflammation have been implicated in several common diseases, such as Alzheimer's disease (AD) and type 1 diabetes (T1D). Of note, herpes simplex virus 1 (HSV-1) has been reported to be associated with AD. We sought to identify the transcriptomic changes due to HSV-1 infection and anti-viral drug (acyclovir, ACV) treatment of HSV-1 infection in dissociated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) to gain potential biological insights into the relevance of HSV-1-induced inflammation in AD and T1D.

Digital Health Tools and Behavioral Strategies to Increase Engagement With Diabetes Self-Management Education and Support: Design and Feasibility of DM-BOOST.

Purpose: The purpose of the study was to describe the development and feasibility of implementing the DM-BOOST program in support of an established diabetes self-management education and support (DSMES) program.

Methods: A patient panel of 4 adults with type 2 diabetes (T2DM) codesigned DM-BOOST. DM-BOOST is a patient-focused program that includes peer-written text messages about diabetes self-management behaviors and digital health training to improve patient portal use and initiate goal setting prior to a scheduled DSMES appointment.

An Early Islet Transcriptional Signature Is Associated With Local Inflammation in Autoimmune Diabetes.

Identifying the early islet cellular processes of autoimmune type 1 diabetes (T1D) in humans is challenging given the absence of symptoms during this period and the inaccessibility of the pancreas for sampling. In this article, we study temporal events in pancreatic islets in LEW.1WR1 rats, in which autoimmune diabetes can be induced with virus infection, by performing transcriptional analysis of islets harvested during the prediabetic period.

The Noble and Often Nobel Role Played by Insulin-Focused Research in Modern Medicine.

Since diabetes was first described over 3,000 years ago, clinicians and scientists alike have sought ever improving treatments en route to a cure. As we approach the 100th anniversary of insulin's first therapeutic use, this article will recount the glorious history associated with research surrounding insulin's isolation, purification, cloning, and subsequent modification. The discovery path we will relate tells the story of many relentless and passionate investigators pursuing ground-breaking research.

Integrated Analysis of the Pancreas and Islets Reveals Unexpected Findings in Human Male With Type 1 Diabetes.

Clinical and pathologic heterogeneity in type 1 diabetes is increasingly being recognized. Findings in the islets and pancreas of a 22-year-old male with 8 years of type 1 diabetes were discordant with expected results and clinical history (islet autoantibodies negative, hemoglobin A1c 11.9%) and led to comprehensive investigation to define the functional, molecular, genetic, and architectural features of the islets and pancreas to understand the cause of the donor's diabetes.

Evaluation of a Diabetes Remote Monitoring Program Facilitated by Connected Glucose Meters for Patients With Poorly Controlled Type 2 Diabetes: Randomized Crossover Trial.

Background: Patients with poorly controlled type 2 diabetes (T2D) experience increased morbidity, increased mortality, and higher cost of care. Self-monitoring of blood glucose (SMBG) is a critical component of diabetes self-management with established diabetes outcome benefits. Technological advancements in blood glucose meters, including cellular-connected devices that automatically upload SMBG data to secure cloud-based databases, allow for improved sharing and monitoring of SMBG data.

Modeling Type 1 Diabetes In Vitro Using Human Pluripotent Stem Cells.

Understanding the root causes of autoimmune diseases is hampered by the inability to access relevant human tissues and identify the time of disease onset. To examine the interaction of immune cells and their cellular targets in type 1 diabetes, we differentiated human induced pluripotent stem cells into pancreatic endocrine cells, including β cells. Here, we describe an in vitro platform that models features of human type 1 diabetes using stress-induced patient-derived endocrine cells and autologous immune cells.

Decreased pancreatic acinar cell number in type 1 diabetes.

Aims/hypothesis: Individuals with longstanding and recent-onset type 1 diabetes have a smaller pancreas. Since beta cells represent a very small portion of the pancreas, the loss of pancreas volume in diabetes is primarily due to the loss of pancreatic exocrine mass. However, the structural changes in the exocrine pancreas in diabetes are not well understood.

Proteomic and Transcriptional Profiles of Human Stem Cell-Derived β Cells Following Enteroviral Challenge.

Enteroviral infections are implicated in islet autoimmunity and type 1 diabetes (T1D) pathogenesis. Significant β-cell stress and damage occur with viral infection, leading to cells that are dysfunctional and vulnerable to destruction. Human stem cell-derived β (SC-β) cells are insulin-producing cell clusters that closely resemble native β cells.

Recovery of viable endocrine-specific cells and transcriptomes from human pancreatic islet-engrafted mice.

Human pancreatic islets engrafted into immunodeficient mice serve as an important model for in vivo human diabetes studies. Following engraftment, islet function can be monitored in vivo by measuring circulating glucose and human insulin; however, it will be important to recover viable cells for more complex graft analyses. Moreover, RNA analyses of dissected grafts have not distinguished which hormone-specific cell types contribute to gene expression.

HLA Class II Antigen Processing and Presentation Pathway Components Demonstrated by Transcriptome and Protein Analyses of Islet β-Cells From Donors With Type 1 Diabetes.

Type 1 diabetes studies consistently generate data showing islet β-cell dysfunction and T cell-mediated anti-β-cell-specific autoimmunity. To explore the pathogenesis, we interrogated the β-cell transcriptomes from donors with and without type 1 diabetes using both bulk-sorted and single β-cells. Consistent with immunohistological studies, β-cells from donors with type 1 diabetes displayed increased Class I transcripts and associated mRNA species.

Human islets expressing HNF1A variant have defective β cell transcriptional regulatory networks.

Using an integrated approach to characterize the pancreatic tissue and isolated islets from a 33-year-old with 17 years of type 1 diabetes (T1D), we found that donor islets contained β cells without insulitis and lacked glucose-stimulated insulin secretion despite a normal insulin response to cAMP-evoked stimulation. With these unexpected findings for T1D, we sequenced the donor DNA and found a pathogenic heterozygous variant in the gene encoding hepatocyte nuclear factor-1α (HNF1A). In one of the first studies of human pancreatic islets with a disease-causing HNF1A variant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction leads to insulin-insufficient diabetes reminiscent of T1D by impacting the regulatory processes critical for glucose-stimulated insulin secretion and suggest a rationale for a therapeutic alternative to current treatment.

IMPROVING AFTER-HOURS CALLS TO ENDOCRINOLOGY FELLOWS.

Objective: To analyze the frequency and nature of after-hours calls to endocrinology fellows and employ interventions to direct appropriate care to primary endocrinologists.

Methods: The on-call fellows logged calls that came to them during the after-hours and marked them as urgent or nonurgent. We analyzed these calls and then implemented interventions to educate patients on calls that can wait until the next business day.

Modifying Enzymes Are Elicited by ER Stress, Generating Epitopes That Are Selectively Recognized by CD4 T Cells in Patients With Type 1 Diabetes.

In spite of tolerance mechanisms, some individuals develop T-cell-mediated autoimmunity. Posttranslational modifications that increase the affinity of epitope presentation and/or recognition represent one means through which self-tolerance mechanisms can be circumvented. We investigated T-cell recognition of peptides that correspond to modified β-cell antigens in subjects with type 1 diabetes.

α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes.

Many patients with type 1 diabetes (T1D) have residual β cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual β cells and α cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant β cells appeared to maintain several aspects of regulated insulin secretion.

Clinical Diabetes Centers of Excellence: A Model for Future Adult Diabetes Care.

Although diabetes research centers are well defined by National Institutes of Health, there is no clear definition for clinical Diabetes Centers of Excellence (DCOEs). There are multiple clinical diabetes centers across the United States, some established with philanthropic funding; however, it is not clear what defines a DCOE from a clinical perspective and what the future will be for these centers. In this Perspective we propose a framework to guide advancement for DCOEs.

Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes.

Enteroviral infections have been associated with the development of type 1 diabetes (T1D), a chronic inflammatory disease characterized by autoimmune destruction of insulin-producing pancreatic beta cells. Cultured human islets, including the insulin-producing beta cells, can be infected with coxsackievirus B4 (CVB4) and thus are useful for understanding cellular responses to infection. We performed quantitative mass spectrometry analysis on cultured primary human islets infected with CVB4 to identify molecules and pathways altered upon infection.

Possible type 1 diabetes risk prediction: Using ultrasound imaging to assess pancreas inflammation in the inducible autoimmune diabetes BBDR model.

Background/aims: Studies of human cadaveric pancreas specimens indicate that pancreas inflammation plays an important role in type 1 diabetes pathogenesis. Due to the inaccessibility of pancreas in living patients, imaging technology to visualize pancreas inflammation is much in need. In this study, we investigated the feasibility of utilizing ultrasound imaging to assess pancreas inflammation longitudinally in living rats during the progression leading to type 1 diabetes onset.

The upside down world of diabetes care medical economics and what we might do to improve it.

Purpose Of Review: Increasingly over the past generation, the American healthcare delivery system has received consistently poor marks with regard to public health outcomes and costs. This review by two seasoned diabetes care providers is intended to shed light on the fundamental flaws we believe to underlie that poor performance, and suggest options for better outcomes and cost efficiencies.

Recent Findings: Despite major advances in diabetes management medications and tools, overall public health with regard to diabetes outcomes remains poor.