**1. Introduction**

At present, we wonder if the current classification of diabetes agrees with the new advances At the molecular genetic level. Every day we can see an exponential increase of type 1 and 2 diabetes anywhere in the world. On the other hand, although several clinical and biochemical characteristics have been described in order to differentiate between both types of diabetes, this does not seem satisfactory for all cases when facing the patient. These characteristics are: (a) The presence of a strong familiar history of diabetes, obesity, *acanthosis nigricans*, and lack of ketoacidosis and auto-antibodies against antigens of pancreatic b-cells islets supports the diagnosis of type 2 diabetes; (b) In contrast, patients with type 1 diabetes are usually thin and with ketoacidosis; almost 90% of them have autoantibodies at the onset of the disease.

Nevertheless, in the last decades numerous reports described adults and adolescents (usually from minority groups) presenting ketoacidosis with lack of antibodies and characteristics of type 2 diabetes such as obesity*, acanthosis nigricans* and/or one significant familiar history of diabetes (Pinhas-Hamiel et al., 1997; Pinhas-Hamiel & Zeitler, 1999;).

Until very recently, most children and adolescents diagnosed with the disease were diagnosed as type 1 diabetes; however, there have recently been numerous reports describing an increase in the number of cases of type 2 diabetes in youngsters (Dabelea et al., 1998; Hathout et al., 2001; Neufeld et al., 1998; Pinhas Hamiel et al., 1996; Scott et al., 1997). Epidemiological data suggests that type 1 and 2 diabetes can coexist in the same family (Kolb & Mandrup-Poulsen, 2005; Libman & Becker, 2003).

The potential importance of formulating a specific diagnosis has been emphasized, as this could determine the type of treatment, associated complications, and outcomes (Fagot et al., 2001; Pinhas-Hamiel & Zeitler, 1999). The current criteria for defining diabetes (Asociación Latinoamericana de Diabetes [ALAD], 2010; American Diabetes Association [ADA], 2010) do not always explain neither the evolution of the disease in different patients or the different responses of individuals to treatments. These facts are suggesting the importance

Diabetes Type 1 and 2: What is Behind a Classification? 289

Currently, the classification of Diabetes mellitus (ADA, 2010; ALAD, 2010) contemplates four well-known major groups: (a) Type 1 Diabetes (T1DM), (b) Type 2 (T2DM), (c) Other

However, on the basis of clinical observations, genetics and molecular research studies carried out in some mixed populations such as those in Latin America (as we shall see below) would point out that this classification is not always adequate; phenotype does not

In order to support our hypothesis that phenotype is not always a proper indicator of genotype, mainly in miscegenated populations (particularly in multifactorial diseases such as diabetes), we will focus our analysis on the research carried out in our population. We believe that the current classification does not always allow an accurate diagnosis, and

Previous research has shown that the Uruguayan population has a particular genetic behavior; in addition to its small size (three millions inhabitants), it presents such a high level of miscegenation that there are individuals that cannot currently identify their ancestors' origin. It has a tri-hybrid origin (Caucasoid, African and Amerindian) but, unlike other Latin-American countries, we do not isolate Amerindian groups (Cardoso et al., 2004; Gascue et al., 2005; Mimbacas et al., 2003, 2004, 2007, 2009; Sans et al., 2011). Thus, this would permit us to think a priori that ethnological factors would (at least in part) cancel each other, therefore eliminating their possible blurring effect on the analysis. When we consider these factors, we can look at our population as an interesting source of information

Several years ago, we focused our investigation on HLA genes associated with type 1 diabetes; our studies (Mimbacas et al., 2003, 2004) were done both by case-control and parent-cases design. We found a very high frequency of specific alleles (DQB1\*0201, DQB1\*0302, DR3, DR4) in our population; although the associated alleles were the same as those of the Caucasian population, their frequencies were different; additionally, we also found that almost all of the patients had associated DR3 and DR4 alleles. Continuing with our investigations, we observed that different polymorphisms of other analyzed genes also showed variations when compared with Caucasian populations or with populations from other origin (Fernández et al., 2009; Mimbacas et al., 2007; Soto et al.,

Conversely, there have been numerous reports describing an increasing number of type 2 diabetes cases in youngsters (Dabelea et al., 1998; Neufeld et al., 1998; Pinhas-Hamiel et al., 1996; Scott et al., 1997). Recently, Lidman and Becker (2003) described the coexistence of types 1 and 2 diabetes in a non-Caucasian individual; afterwards, Pozzili and Buzzetti (2007) described more cases and defined the possibility of a new type of diabetes, proposing more characterization studies in different ethnic groups. In a recent paper (Mimbacas et al., 2011) we described a case report that, according to our criteria, showed

In what it has to do with this possibility of a new expression of diabetes, it is important to determine the influence of the genetic and auto-immune factors underlying the consequent

destruction of the beta islets, which would pass unnoticed in a classic phenotype.

specific types of diabetes, and (d) Gestational diabetes.

therefore the treatment plan is not always the correct one.

always reflect genotype (Mimbacas et al., 2009).

for the study of different issues on diabetes.

2004; Zorrilla et al., 2006).

this type of presentation of the disease.

**3. Miscegenated population** 

of considering the genetic background of individuals for their categorization and subsequent treatment. A highly controversial topic has recently aroused worldwide: is there a new type of diabetes with mixed characteristics of both types? Different authors have identified this variety as "Double Diabetes" or "Hybrid Diabetes" (Libman & Becker, 2003; Mimbacas et al., 2011; Pozzilli & Buzzetti; 2007; Pozzilli & Guglielmi., 2007); but, are we really facing a new type of diabetes unknown before?, or is it a phenomenon not demonstrated until present due to the use of former inappropriate methodologies or instrumentations? If it is a new expression, why does it appear now? Is there an evolutionary process involved? How?

We will try to discuss these subjects in this chapter.
