**Latent Autoimmune Diabetes in Adults**

**Latent Autoimmune Diabetes in Adults**

#### Javier Eduardo Escober Torres Javier Eduardo Escober Torres Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.72685

#### **Abstract**

Latent Autoimmune Diabetes in Adults (LADA) is the term used to describe adults who have a slowly progressive form of diabetes mellitus (DM) of autoimmune etiology, but that may be treated initially without insulin. Although the American Diabetes Association (ADA) currently does not recognize this disease as a specific type, there is increasing information about it, as well as groups dedicated to its study. LADA shares some immunological and genetic aspects with DM type 1, it affects an age group that is typically affected by type 2 DM. Therefore, it could be considered a type of intermediate diabetes. This process can be detected by specific antibodies in the peripheral blood, months or even years before the clinical onset of the disease. Diagnosis is based on clinical and laboratory criteria: age of onset, initial response to oral hypoglycemic agents and the presence of specific antibodies for diabetes. Although the definitive treatment is insulin, glitazones may be useful in early stages of the disease. Currently, its management represents a challenge for the physician, including specialists, and it is a form of DM to keep in mind.

DOI: 10.5772/intechopen.72685

**Keywords:** diabetes mellitus type 1, diabetes mellitus type 2, adult latent autoimmune diabetes, autoimmunity, glutamic acid decarboxylase

#### **1. Introduction**

Diabetes mellitus (DM) is a complex and heterogeneous disease from a physiopathological point of view and often exceeds the somewhat rigid margins of the categories included in the current classification [1].

In 1986 Groop et al. reported a subgroup of diabetic patients who had cells specific for pancreatic beta cell (c-β) function, with characteristics different from the classic type 1 and type 2 DM [2]. Type 1 DM is caused by an autoimmune response that produces a progressive destruction of pancreatic (c-β). This process can be detected by specific antibodies in the peripheral blood, months or even years before the clinical onset of the disease [3].

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

The term Latent Autoimmune Diabetes in the Adult (LADA, Latent Autoimmune Diabetes of the Adult) by its abbreviations in English; it was coined by Tuomi et al. to describe patients with a slowly progressive form of autoimmune or type 1 DM who could be treated initially without insulin [4].

Both diseases, both DM type 1 and LADA; present specific antibodies: anti-decarboxylase of glutamic acid (anti-GAD), anti-beta cells (ICA), anti-tyrosine phosphatase (IA-2) and anti-insulin, the first of which is the most prevalent, followed by ICA [5, 6]; in more than 10% of adults with presumed DM type 2 (DM2) [7, 8], so LADA is the most prevalent form of autoimmune diabetes in adults and probably also the most prevalent form of autoimmune diabetes in general [9].

Clinically, these patients are difficult to distinguish from type 2 diabetic subjects who are positive for the markers that characterize patients with type 1 diabetes.

The presence or absence of islet autoantibodies is one of the most direct ways to distinguish between type 1 and type 2 diabetic patients [10].

And, although LADA is undoubtedly related to type 1 DM, its clinical presentation frequently features traits attributable to type 2 DM and is often misdiagnosed and treated for significant periods of time. This is helped by the fact that the current diagnostic criteria used to identify this variant of diabetes are imprecise and subject to controversy.

Although the American Diabetes Association (ADA) currently does not recognize this disease as a specific type, there is increasing information about it, as well as groups dedicated to its study.

**3. Genetics**

response [28].

diabetes, especially when non-insulin requiring.

comparison with the general population [26, 27].

Pathological studies have proposed that LADA and type 1 DM share physiopathological and genetic aspects; such as genes (HLA, INS VNTR and PTPN22) and with respect to DM type 2 (TCF7L2) [26], which suggest that it may represent a genetic admixture of the two types of

**Table 1.** Prevalence of positive glutamic acid decarboxylase antibodies (late autoimmune diabetes in adults) in subjects

**Author Country Type of study Universe Prevalence %**

density

density

density

Based on population

1122 9.3

Latent Autoimmune Diabetes in Adults http://dx.doi.org/10.5772/intechopen.72685 25

2076 2.8

4134 4.2

Adeleye et al. [13] Southwest of Nigeria Based on the clinic 160 11.9 Ipadeola et al. [14] Southwest of Nigeria Based on the clinic 235 14.0 Agyei-Frempong et al. [15] Ghana Based on the clinic 120 11.7 Otieno et al. [16] Kenya Based on the clinic 124 5.7 Hwangbo et al. [17] Korea Based on the clinic 462 4.3

Arikan et al. [21] Turkey Based on the clinic 54 31.0 Brahmkshatriya et al. [22] India Based on the clinic 500 5.0 Lerman et al. [23] Mexico Based on the clinic 83 3.6

Tuomi et al. [18] Finland Based on population

Bosil et al. [19] Italy Based on population

Europe

Zinman et al. [20] North America and

with type 2 diabetes among different population groups.

It is known that LADA has a higher frequency of human histocompatibility antigens (HLA) characteristic of DM type 1: HLA-DR3 (28% of patients), DR4 (27%) and DR 3/4 (22%), in

The dilemma persists in the fact whether this genetic mixture represents a totally different

It is important to mention that in all the genome-wide association studies directed to the exome sequencing carried out until now or the sequencing of the whole genome exome, they

As mentioned, both diseases have specific antibodies. Concomitantly, a decrease in the frequency and activation of "natural killer" cells in peripheral blood compared with healthy individuals has been demonstrated, which translates into a defect in the immune

disease syndrome or is part of a continuum of an autoimmune process.

have not yet been carried out in large cohorts of adult autoimmune patients.
