Immune therapy in type 1 diabetes mellitus

  title={Immune therapy in type 1 diabetes mellitus},
  author={{\AA}ke Lernmark and Helena Elding Larsson},
  journal={Nature Reviews Endocrinology},
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder directed against the β cells of the pancreatic islets. The genetic risk of the disease is linked to HLA-DQ risk alleles and unknown environmental triggers. In most countries, only 10–15% of children or young adults newly diagnosed with T1DM have a first-degree relative with the disease. Autoantibodies against insulin, GAD65, IA-2 or the ZnT8 transporter mark islet autoimmunity. These islet autoantibodies may already have developed in… 

Advances in immunotherapy of type I diabetes.

Diabetes as autoimmune disease-Diabetes type

T1D remains the most common form of diabetes in childhood, accounting for approximately two-thirds of new diagnoses in patients ≤19 years of age in the United States, despite the increasing rate of type 2 diabetes.

Depleting T Cells in Newly Diagnosed Autoimmune (Type 1) Diabetes—Are We Getting Anywhere?

The prevalence and incidence of type 1 diabetes are diverse, explained in part by the heterogeneous distribution of HLA genetic factors on chromosome 6 that control the body’s way of dealing with infectious diseases.

Risk Factors and Primary Prevention Trials for Type 1 Diabetes

The purpose of this review is to provide an overview of this disorder's pathogenesis, risk factors that cause the disease, as well as to bring forward an ideal approach to prevent and cure the disorder.

Risk Factors and Primary Prevention Trials for Type 1

The purpose of this review is to provide an overview of this disorder’s pathogenesis, risk factors that cause the disease, as well as to bring forward an ideal approach to prevent and cure the disorder.

Overcoming barriers in clinical islet transplantation: current limitations and future prospects.

Development of the “artificial pancreas,” an integrated closed-loop control system that combines continuous glucose monitoring with subcutaneous insulin infusion, has been shown to significantly improve glycemic control, although refinement for routine ambulatory use is still in evolution.

Islet-Derived CD4 T Cells Targeting Proinsulin in Human Autoimmune Diabetes

It is shown that proinsulin peptides are targeted by islet-infiltrating T cells from patients with type 1 diabetes with a short disease duration with high-risk HLA genes using a direct T-cell receptor (TCR) sequencing approach without long-term cell culture.

Advances in the cellular immunological pathogenesis of type 1 diabetes

This review outlines the cellular immunological mechanism of type 1 diabetes, with a particular emphasis to T lymphocyte and natural killer cells, and provides the effective immune therapy in T1D, which is approached at three stages.



Modulating the natural history of type 1 diabetes in children at high genetic risk by mucosal insulin immunization

The proposed Pre-POINT (Primary Oral/intranasal INsulin Trial) aims to identify an optimal insulin dose and route of application that is well tolerated and can induce an immune response to insulin for additional use in a phase II/III primary prevention trial in children at risk.

Pancreatic Islet Autoantibodies as Predictors of Type 1 Diabetes in the Diabetes Prevention Trial–Type 1

The data indicate that the number of autoantibodies is predictive of type 1 diabetes, however, mIAA is less predictive ofType 1 diabetes than other autoantibia, and must be carefully considered in planning prevention trials fortype 1 diabetes.

GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus.

Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period, and the primary outcome did not differ significantly between the combined active-drug groups and the placebo group.

Immunomodulatory therapy to preserve pancreatic β-cell function in type 1 diabetes

The current knowledge of the immunopathogenesis of type 1 diabetes and how this information has been translated into clinical trials is discussed and next-generation combination immunotherapies that may be administered as adjuvant therapy at time of diagnosis are discussed.

Primary Dietary Intervention Study to Reduce the Risk of Islet Autoimmunity in Children at Increased Risk for Type 1 Diabetes

Delaying gluten exposure until the age of 12 months is safe but does not substantially reduce the risk for islet autoimmunity in genetically at-risk children.

Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes.

Short-term treatment with CD3 antibody preserves residual beta-cell function for at least 18 months in patients with recent-onset type 1 diabetes, as suggested by the results of a phase 1 study.

T Cell Recognition of Autoantigens in Human Type 1 Diabetes: Clinical Perspectives

Developing T-cell assays in diabetes autoimmunity is expected to help defining autoantigens and epitopes that drive the disease process, to pinpoint key functional features of epitope-specific T lymphocytes along the natural history of diabetes and to pave the way towards therapeutic strategies to induce immune tolerance to β-cells.

Neonatal Bacille Calmette-Guerin vaccination and type 1 diabetes.

There is substantial interest in whether immunostimulation with BCG could be used as a primary, secondary, or tertiary vaccination strategy for type 1 diabetes.

Dietary intervention in infancy and later signs of beta-cell autoimmunity.

Dietary intervention during infancy appears to have a long-lasting effect on markers of beta-cell autoimmunity--markers that may reflect an autoimmune process leading to type 1 diabetes.