Latent autoimmune diabetes in adults: A distinct but heterogeneous clinical entity

Abstract

Latent autoimmune diabetes in adults (LADA) accounts for 2%-12% of all cases of diabetes. Patients are typically diagnosed after 35 years of age and are often misdiagnosed as type II Diabetes Mellitus (DM). Glycemic control is initially achieved with sulfonylureas but patients eventually become insulin dependent more rapidly than with type II DM patients. Although they have a type II DM phenotype, patients have circulating beta (β) cell autoantibodies, a hallmark of type I DM. Alternative terms that have been used to describe this condition include type 1.5 diabetes, latent type I diabetes, slowly progressive Insulin Dependent Diabetes Mellitus, or youth onset diabetes of maturity. With regards to its autoimmune basis and rapid requirement for insulin, it has been suggested that LADA is a slowly progressive form of type I DM. However, recent work has revealed genetic and immunological differences between LADA and type I DM. The heterogeneity of LADA has also led to the proposal of criteria for its diagnosis by the Immunology of Diabetes Society. Although many workers have advocated a clinically oriented approach for screening of LADA, there are no universally accepted criteria for autoantibody testing in adult onset diabetes. Following recent advances in immunomodulatory therapies in type I DM, the same strategy is being explored in LADA. This review deals with the contribution of the genetic, immunological and metabolic components involved in the pathophysiology of LADA and recent approaches in screening of this distinct but heterogeneous clinical entity.

The hereditary predisposition features of latent autoimmune diabetes of adults

“…Исходя из предположе-ния, что в основе развития СД1 и МПАДВ лежат различные патогенетические процессы, общими для которых являются аутоиммунные нарушения, а клиническая манифестация МПАДВ протекает ана-логично СД2, предлагалось введение термина СД1,5 типа [2]. К. Hamaguchi и соавт.…”

“…К. Hamaguchi и соавт. [2] оставляют откры-тым вопрос о том, является ли заболевание у этих пациентов отдельной формой СД, либо имеет место СД1 с поздней манифестацией. На долю МПАДВ приходятся 2-12% всех случаев СД и 10-20% слу-чаев СД взрослых [3].…”

“…По мере развития патологического процесса (в среднем от 6 мес до 5 лет после диагностирования СД) на фоне пер-оральной сахароснижающей терапии ухудшаются показатели гликемического контроля и возникает необходимость в переводе больных на инсулин [1]. С учетом основного механизма поражения β-клеток верификация диагноза МПАДВ основана на выяв-лении аутоантител к GAD (GAD ab), цитоплазмати-ческому антигену (ICA ab), тирозинфосфатазе (IA-2A ab), инсулину (IAA ab) [2]. В отличие от СД1 при МПАДВ может наблюдаться иммунотолерантность к антигенам β-клеток, что способствует спонтанной защите клеток поджелудочной железы от обширной Т-клеточной деструкции [5].…”

Diabetic Ketoacidosis With Acute Necrotizing Pancreatitis as First Presentation in Latent Autoimmune Diabetes in Adult

“…The current diagnostic criteria for LADA include: 1) being over 30 years of age, 2) not requiring insulin for 6 months, 3) having specific diabetes associated autoantibodies, including autoantibodies to glutamic acid decarboxylase 65 (GADA), insulinoma-associated antigen IA-2 (IA-2A), islet cells (ICA) and zinc transporter 8 (ZnT8A) [1]. LADA is seen in 2-12% of all diabetic cases, but is presumed to be underdiagnosed due to the difficulty of making the diagnosis clinically [2]. In some unusual cases, the first presentation of LADA is diabetic ketoacidosis (DKA).…”

Upregulation of Proinflammatory Cytokine Production in Response to Bacterial Pathogen-Associated Molecular Patterns in Dogs with Diabetes Mellitus Undergoing Insulin Therapy

“…1,2 Insulin-deficiency diabetes mellitus is characterized by progressive loss of pancreatic beta cells or beta-cell hypoplasia/abiotrophy and an absolute deficiency of insulin and is synonymous with type 1 diabetes mellitus (T1DM) in people with features of latent autoimmune diabetes of adults (type 1.5 diabetes mellitus). [1][2][3][4] With dogs, there are genetic, sex (female phenotype), as well as breed predilections, and age distribution is predominately middle age to early geriatric. 2,5 Standard medical management for T1DM in dogs consists of administration of intermediate or longacting insulin and dietary alterations.…”