Type I Diabetes I: Introduction

Type 1 diabetes mellitus is a chronic metabolic disorder characterized by an absolute deficiency of insulin resulting from the autoimmune destruction of pancreatic β-cells. Although it can occur at any age, it is most commonly diagnosed in childhood, adolescence, or early adulthood. The loss of insulin production impairs cellular glucose uptake, resulting in persistent hyperglycemia and necessitating lifelong insulin therapy.

Autoimmune Destruction of β-Cells

The hallmark of type 1 diabetes is an immune-mediated attack on the β-cells of the pancreatic islets. This process develops gradually and often remains clinically silent until most β-cell mass is lost. Autoreactive T lymphocytes play a central role, infiltrating the islets and initiating cell-mediated cytotoxicity. The autoimmune response is accompanied by the production of autoantibodies directed against key β-cell antigens, including insulin, glutamic acid decarboxylase 65 (GAD65), and the tyrosine phosphatase IA-2. These autoantibodies serve as important markers of disease risk and are frequently detectable long before symptoms appear.

Genetic Susceptibility and Environmental Triggers

Genetic predisposition significantly influences the development of type 1 diabetes. Variants in the Human Leukocyte Antigen (HLA) region on chromosome 6, particularly the HLA-DRB103 and HLA-DRB104 alleles, confer the strongest known genetic risk. These alleles shape antigen presentation and may promote loss of immune tolerance to β-cell antigens. Individuals with a first-degree relative affected by type 1 diabetes have a higher likelihood of developing the disease, reflecting shared genetic and environmental factors.

Environmental influences further modify risk in genetically susceptible individuals. Viral infections, early-life exposures, and other environmental triggers may initiate or accelerate autoimmunity by altering β-cell antigens or stimulating immune activation. Together, these mechanisms culminate in progressive β-cell destruction and the clinical onset of type 1 diabetes.