Autoimmune diabetes in adults
المؤلف:
Holt, Richard IG, and Allan Flyvbjerg
المصدر:
Textbook of diabetes (2024)
الجزء والصفحة:
6th ed , page217-218
2025-11-16
26
In the early 1980s, among people of white European ancestry, over 90% of all individuals with diabetes diagnosed young were considered to have classic type 1 diabetes due to autoimmune islet destruction with acute ketosis and absolute insulin deficiency. Autoantibodies against pancreatic islet antigens, such as glutamic acid decarboxylase (GAD), are markers for type 1 diabetes. In the early 1990s, Zimmet et al. first described a form of adult- onset auto immune diabetes, albeit with phenotypes resembling type 2 diabetes, so called latent autoimmune diabetes in adults (LADA). In 2019, the World Health Organization (WHO) formally recognized this form of diabetes and renamed it as a slowing evolving immune- mediated diabetes of adults under the classification category of a hybrid form of diabetes, although the nomenclature of LADA is still widely used. Individuals with LADA often carry other autoantibodies associated with coeliac disease and adrenal and thyroid disorders, suggesting it is part of a spectrum of autoimmune diseases. More recent studies indicate that LADA might be a hybrid of type 2 diabetes and autoimmune diabetes. Individuals with LADA have a high frequency of both type 1 diabetes–susceptibility genotype and type 2 diabetes–susceptibility genotypes, suggesting that these aetiologies were not mutually exclusive. In the UK Prospective Diabetes Study (UKPDS), approximately 10% of individuals with type 2 diabetes had GAD autoantibodies, the majority of whom eventually progressed to insulin dependency.
Depending on the selection criteria of clinical definition, age of diagnosis, ethnicity, and assay methodologies, the prevalence of LADA in individuals with type 2 diabetes might vary considerably. Reports from other ethnic groups suggested an estimated 10% prevalence of LADA in adult populations with a clinical presentation of type 2 diabetes. In a prospective cohort of Chinese adults with young- onset diabetes, 8.1% of individuals had GAD autoantibodies suggestive of LADA. Compared to their counterparts without GAD autoantibodies, individuals with LADA were highly responsive to insulin treatment with a reduction of glycated haemoglobin (HbA1c) of 2.3% (25 mmol/mol) versus 0.7% (7 mmol/ mol) in individuals without LADA at 12 months. Although individuals with LADA had fewer cardiometabolic risk factors and were less likely to have cardiovascular events than their counter parts with a type 2 diabetes presentation, they were three times more likely to develop end- stage kidney disease than those with a type 1 diabetes presentation. The levels of GAD autoantibodies correlate with pancreatic β- cell function. Individuals with high GAD autoantibody titre had more rapid decline in β- cell function as measured using homeostasis model assessment (HOMA2- B) and were more likely to reach β- cell failure.
The prompt diagnosis of LADA is clinically important, since early use of insulin was often needed to improve glycaemic levels to prevent accelerated loss of β- cell function. Impaired β- cell response is often evident at diagnosis and early use of insulin might reduce the adverse effects of glucotoxicity on β cells. However, there is no evidence that early insulin implementation has any effects on the risk of late diabetes complications. Limited evidence suggests that treatment with sulfonylureas was associated with more rapid progression to β- cell failure, whereas treatment with dipeptidyl- peptidase 4 inhibitors might be protective.
Apart from clinical suspicion, HLA studies might distinguish LADA from classic type 1 diabetes. In white European populations, LADA was associated with HLA DQA1- DQB1*0102(3)-*0602(3)/X, which was uncommon in individuals with typical type 1 diabetes. In a consensus statement from an international expert panel, measurement of C- peptide levels as a proxy for endogenous pancreatic β- cell function was recommended to guide diagnosis and management in LADA. For C- peptide levels 0.7 nmol/l, individuals should be managed as type 1 diabetes and type 2 diabetes, respectively. For those in the grey zone (C- peptide ≥0.3 and ≤0.7 nmol/l), insulin should be considered in combination with other therapies to attenuate the progression of β- cell failure.
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