Latent Autoimmune Diabetes in Adults (LADA): From Immunopathogenesis to Immunotherapy

Abstract

Latent autoimmune diabetes in adults (LADA) is a type of diabetes characterized by slow autoimmune damage of pancreatic β cells without insulin treatment in the early clinical stage. There are differences between LADA and classical type 1 diabetes (T1D) and type 2 diabetes (T2D) in genetic background, autoimmune response, rate of islet function decline, clinical metabolic characteristics, and so on. The disease progression and drug response of patients with LADA are closely related to the level of islet autoimmunity, thus exploring the pathogenesis of LADA is of great significance for its prevention and treatment. Previous studies reported that adaptive immunity and innate immunity play a critical role in the etiology of LADA. Recent studies have shown that the intestinal microbiota which impacts host immunity hugely, participates in the pathogenesis of LADA. In addition, the progression of autoimmune pancreatic β cell destruction in LADA is slower than in classical T1D, providing a wider window of opportunities for intervention. Therefore, therapies including antidiabetic drugs with immune-regulation effects and immunomodulators could contribute to promising interventions for LADA. We also shed light on potential interventions targeting the gut microbiota and gut-associated immunity, which may be envisaged to halt or delay the process of autoimmunity in LADA.

Morphofunctional State of Pancreas in Rats With Diabetes Mellitus

“…In histological sections of pancreas from a patient with a long, progressive course of type 1 diabetes, it was found that endocrine part of human pancreas, unlike in animals, presents a mosaic pattern with areas containing only insulinocytes and, conversely, areas of islets without insulinocytes. These results indicate the heterogeneity of disease and are evidence of high frequency of a latent autoimmune course in humans [28].…”

Newly diagnosed type 1 diabetes mellitus in a human immunodeficiency virus-infected patient with antiretroviral therapy-induced immune reconstitution inflammatory syndrome: a case report

“…LADA is a slow-progressing type of autoimmune diabetes. As with T1DM, LADA may occur due to pancreatic beta cell dysfunction resulting in inadequate production of insulin [ 13 ]. Autoimmune antibodies can slowly destroy the pancreatic beta cells, with both LADA and T1DM reported to share characteristics of immunological dysfunction, such as pancreatic β cell-specific autoantibodies and alterations in the immunophenotype of immune cells [ 14 ].…”

Gut Microbiota, LADA, and Type 1 Diabetes Mellitus: An Evolving Relationship

“…In conclusion, LADA patients have a change in gut microbiota which closely resembles that of type 1 diabetes mellitus patients and has significant variations compared to the microbiota of healthy people. The role of immunity resulting from the proper development and functioning of the gut microbiota and the onset of LADA has therefore been examined again in some recent work [ 64 ], and the role of short-chain fatty acids produced by symbiotic microorganisms, with their regulatory function towards cytokines and T cells, has once again become increasingly crucial.…”