Differences in the genetic background of latent autoimmune diabetes in adults (LADA) and type 1 diabetes mellitus

Vatay, Ágnes; Rajczy, Katalin; Pozsonyi, Éva; Hosszúfalusi, Nóra; Prohászka, Zoltán; Füst, George; Karádi, István; Szalai, Csaba; Grosz, Andrea; Bártfai, Zoltán; Pánczél, Pál

doi:10.1016/s0165-2478(02)00156-6

Cited by 44 publications

(35 citation statements)

References 28 publications

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“…The gene for tumor necrosis factor-␣ is also in the major histocompatibility complex region and there is an allelic polymorphism within the promoter region. The TNF2 allele was significantly lower in LADA compared with type 1 diabetes or nondiabetic control subjects (33).…”

Section: Geneticsmentioning

confidence: 85%

Is Latent Autoimmune Diabetes in Adults Distinct From Type 1 Diabetes or Just Type 1 Diabetes at an Older Age?

et al. 2005

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Diabetes is classified clinically into two types: type 1 and type 2 diabetes. Type 1 diabetes is an autoimmune diabetes, whereas, in contrast, type 2 diabetes is nonautoimmune. However, there is a group of phenotypic adult type 2 diabetic patients (ϳ10%) who have islet autoantibodies similar to type 1 diabetes. These patients are said to have latent autoimmune diabetes in adults (LADA) or type 1.5 diabetes. T-cells reacting with islet proteins have been demonstrated in type 1 and type 1.5 diabetic patients. In contrast, classic autoantibody-negative type 2 diabetic patients are also negative for T-cell responses to islet proteins. Therefore, we questioned whether type 1 and type 1.5 diabetes are similar or different autoimmune diseases. We have investigated the immunological and metabolic differences between type 1, type 1.5, and classic type 2 diabetic patients. We have identified autoantibody differences, differences in islet proteins recognized by T-cells, and differences in insulin resistance. We have also identified a small group of patients who have T-cells responsive to islet proteins but who are autoantibody negative. These patients appear to be similar to type 1.5 patients in having decreased stimulated C-peptide values. These immunological differences between type 1 and type 1.5 diabetes suggest at least partially distinct disease processes. Diabetes 54 (Suppl. 2):S62-S67, 2005 T he finding nearly simultaneously by two groups in 1974 (1,2) that islet cell antibodies (ICAs) were common in the sera of patients with type 1 diabetes (type 1 diabetes) provided strong evidence that the ␤-cell lesion of type 1 diabetes was autoimmune in nature. Shortly thereafter, it was published that ϳ11% of patients with type 2 diabetes were also positive for ICAs and that this ICA ϩ subset of type 2 diabetic patients tended to fail sulfonylurea therapy and needed insulin treatment earlier than ICA Ϫ type 2 diabetic patients (3). Many other groups have also identified a subset of phenotypic type 2 diabetic patients who are positive for the antibodies commonly found in type 1 diabetes; this subset has been said to have type 1.5 diabetes, latent autoimmune diabetes in adults (LADA), slowly progressive IDDM, latent type 1 diabetes, youth-onset diabetes of maturity, latent-onset type 1 diabetes, and antibody-positive non-insulin-dependent diabetes (4 -6) ( Table 1). Although the different names have caused some confusion, the finding of this subset of phenotypic type 2 diabetic patients by many different investigators rather than just one or two groups confirms their existence as an important subset of phenotypic type 2 diabetic patients.Probably the greatest area of confusion involves the distinction of LADA from type 1 diabetes occurring in individuals over the age of 30 -35 years. Epidemiologic evidence suggests that type 1 diabetes peaks around puberty and again around age 40 years (7), and Nerup and colleagues (8) have suggested that the incidence of type 1 diabetes is approximately equivalent below and above age 20 years...

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Section: Geneticsmentioning

confidence: 85%

Is Latent Autoimmune Diabetes in Adults Distinct From Type 1 Diabetes or Just Type 1 Diabetes at an Older Age?

et al. 2005

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“…Compared with nonautoimmune T2D patients, autoimmune T2D patients are reportedly more commonly positive for HLA-DR3 and -DR4 and their associated DQ␤1 alleles 0201 and 0302, which are haplotypes strongly linked to a predisposition to childhood T1D (29, 30, 47 ). Other non-HLA genetic differences between T1D and T2D are seen in the MICA 4 (MHC class I polypeptide-related sequence A) gene (48,49 ) and an allelic polymorphism within the promoter region of the TNF (tumor necrosis factor) gene (the TNF2 allele) (50 ). Recent genomewide association studies have demonstrated a link between the polymorphisms in the SLC30A10 (solute carrier family 30, member 10; also known as ZNT8) gene and T2D, although ZnT8 autoantibodies are rarely detected in phenotypic T2D (51-53 ) but are common in T1D patients.…”

Section: Geneticsmentioning

confidence: 99%

Is Diabetes Mellitus a Continuous Spectrum?

Brooks-Worrell

Palmer

2011

Clinical Chemistry

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BACKGROUND Diabetes mellitus has been historically divided into type 1 and type 2 diabetes, with type 1 being an autoimmune disease and type 2 being primarily a metabolic disease. CONTENT The current diabetes classification scheme needs to be reevaluated because of the accumulating evidence of immune system involvement in the pathophysiology of type 2 diabetes. SUMMARY There are similarities and differences between type 1 and type 2 diabetes with regard to pathogenesis, pathophysiology, and genetics. We propose a resolution to the dilemma of the current classification scheme.

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“…Other candidate genes in LADA include those for cytotoxic T lymphocyte-associated protein 4 [12] and TNF-2 [30].…”

Section: Other Genesmentioning

confidence: 99%

Latent autoimmune diabetes in adults (LADA) should be less latent

et al. 2005

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'Latent autoimmune diabetes in adults' (LADA) is the term coined to describe adults who have a slowly progressive form of autoimmune or type 1 diabetes that can be treated initially without insulin injections. The diagnosis of LADA is currently based on three clinical criteria: (1) adult age at onset of diabetes; (2) the presence of circulating islet autoantibodies, which distinguishes LADA from type 2 diabetes; and (3) insulin independence at diagnosis, which distinguishes LADA from classic type 1 diabetes. The prevalence of LADA in adults presenting with non-insulin-requiring diabetes is approximately 10%. Recognition of LADA expands the concept and prevalence of autoimmune diabetes, but LADA remains poorly understood at both a clinical and research level. In this perspective, we review the nomenclature, diagnostic criteria, genetics, pathology and therapy of LADA, to arrive at recommendations that might advance knowledge and management of this form of diabetes.

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Differences in the genetic background of latent autoimmune diabetes in adults (LADA) and type 1 diabetes mellitus

Cited by 44 publications

References 28 publications

Is Latent Autoimmune Diabetes in Adults Distinct From Type 1 Diabetes or Just Type 1 Diabetes at an Older Age?

Is Latent Autoimmune Diabetes in Adults Distinct From Type 1 Diabetes or Just Type 1 Diabetes at an Older Age?

Is Diabetes Mellitus a Continuous Spectrum?

Latent autoimmune diabetes in adults (LADA) should be less latent

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