3.3.0.0 Immune-Mediated Diabetes
This form, previously called “insulin-dependent diabetes” or “juvenile-onset diabetes,” accounts for 5–10% of diabetes and is due to cellular-mediated autoimmune destruction of the pancreatic β-cells. Autoimmune markers include islet cell autoantibodies and autoantibodies to GAD (GAD65), insulin, the tyrosine phosphatases IA-2 and IA-2β, and ZnT8. Type 1 diabetes is defined by the presence of one or more of these autoimmune markers. The disease has strong HLA associations, with linkage to the DQA and DQB genes. These HLA-DR/DQ alleles can be either predisposing or protective.
The rate of β-cell destruction is quite variable, being rapid in some individuals (mainly infants and children) and slow in others (mainly adults). Children and adolescents may present with DKA as the first manifestation of the disease. Others have modest fasting hyperglycemia that can rapidly change to severe hyperglycemia and/or DKA with infection or other stress. Adults may retain sufficient β-cell function to prevent DKA for many years; such individuals eventually become dependent on insulin for survival and are at risk for DKA. At this latter stage of the disease, there is little or no insulin secretion, as manifested by low or undetectable levels of plasma C-peptide. Immune-mediated diabetes commonly occurs in childhood and adolescence, but it can occur at any age, even in the 8th and 9th decades of life.
Autoimmune destruction of β-cells has multiple genetic predispositions and is also related to environmental factors that are still poorly defined. Although patients are not typically obese when they present with type 1 diabetes, obesity should not preclude the diagnosis. People with type 1 diabetes are also prone to other autoimmune disorders such as Hashimoto thyroiditis, Graves disease, Addison disease, celiac disease, vitiligo, autoimmune hepatitis, myasthenia gravis, and pernicious anemia (see Section 4 “Comprehensive Medical Evaluation and Assessment of Comorbidities”).