**5. Clinical presentation and relationship with chronic diseases**

Andersen et al. mentions that patients with LADA have a higher body mass index (BMI) than type 1 diabetics, but less than type 2. The condition of normal weight is the most frequent nutritional status [32].

However, it is not a Sine Qua Non standard in its diagnosis.

#### **5.1. Metabolic characteristics**

**4. Why are LADA and non-diabetic type 1?**

**4.1. When to think about LADA?**

1. Appearance in adulthood, usually after 30 years

Autoimmunity Present (ICA

Source: Pollak et al. [31].

1. Less marked exposure to environmental factors.

3. Intermittent crisis of autoimmune aggression.

2. Lower specific antibody titers.

5. Acquired immunotolerance.

2. Presence of specific auto antibodies, anti-GAD the most prevalent

predominates)

**Table 4.** Characteristics of DM type 1, LADA and DM type 2.

BMI <25 kg/m2

26 Diabetes and Its Complications

been formulated that explain the appearance of LADA. See **Table 2**.

71% specificity for the identification of LADA patients [25, 30].

Taking into account its subsequent and less aggressive presentation, different arguments have

Some characteristics have been related, which in order of frequency associated with the disease in comparison with type 2 diabetics are: age of onset <50 years, symptoms of acute onset,

It is described that the presence of 2 or more of these criteria presents a 90% sensitivity and

and personal or family history of autoimmune disease.

In case of suspicion, specific antibodies should be requested to confirm the diagnosis.

The last three points would be the result of a better protection/risk gene balance compared to type 1 diabetics [3, 29].

3. There is no need for insulin therapy at the onset of the disease, which should last at least 6 months

**Characteristics DM type 1 LADA DM type 2** Age of onset of the disease Childhood or adulthood Adulthood Adulthood Metabolic syndrome Similar general population Similar general population 80 and 90% Ketoacidosis Frequent Infrequent Absent

Present (predominates anti GAD) Absent

Late

therapy requirement

**Table 3.** LADA diagnostic criteria, proposed by Immunology of Diabetes Society (IDS).

Insulin therapy Since the diagnosis Approximately 6 months without

4. Greater capacity to regenerate beta cells and protection against the apoptotic process.

**Table 2.** Postulates of Pozzilli and Di Mario [3], which differentiates LADA from DM type 1.

Patients with adult onset autoimmune diabetes generally have a better metabolic profile than those with type 2 diabetes, with lower levels of triglycerides, higher HDL cholesterol and lower BMI, waist/hip ratio, and blood pressure [18, 33–37].

#### *5.1.1. Body mass index and LADA*

A clinical point of view that persists is that patients with LADA are usually thin at the time of diagnosis [5] similar to children with diabetes type 1. However, documentation of BMI in LADA populations of European extraction does not support this point of view. Most of the larger LADA cohort studies report an average BMI in categories of overweight or obesity (BMI > 25.0 kg/m2 ) [20, 38–40] and most report a BMI similar to the diabetes type 2 cohorts [20, 38, 40]. Therefore, a normal BMI (<25.0 kg/m2 ) should not be a diagnostic criterion for LADA.

#### *5.1.2. Metabolic syndrome and LADA*

The increase in the prevalence of metabolic syndrome (MetS) worldwide is alarming, even more so if we take into account that it is considered a risk factor for the development of diabetes, or a pre-diabetic state. The impact of MetS has been demonstrated by the increase in subclinical atherosclerotic disease in patients with the syndrome, even without the diagnosis of diabetes [41]. In countries such as the United States and Mexico, the prevalence of MetS is around 25% of its adult population [42].

Through a cross-sectional population-based study conducted by Wong-McClure et al. they claim that the general prevalence of MetS in Central America is high, being higher in Honduras (21.1%, CI: 16.4–25.9) than in the other countries of the isthmus [43].

Given the presented and due to the absence of data in primary care in Honduras [44], a descriptive study is carried out; in which the prevalence of MetS was determined using the criteria of the third report of the Group of Experts in Adult Treatment (Adult Treatment Panel III) of the National Program of Education on Cholesterol or by its acronym in English «National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) [45] being 65.8%.

Multiple studies on MetS and its relationship with DM type LADA estimate that at least 30% of patients diagnosed with type LADA have metabolic disorders [36].

**6. Clinical features**

had an earlier age [53].

**7. Complications**

also present in LADA [55].

**7.1. Chronic complications**

diabetes that can be controlled only with diet.

and an increased likelihood of treatment with insulin [18, 35, 48].

than patients with GADA high titer [18, 33, 35, 48].

At the time of diagnosis, the clinical phenotype of patients with apparent autoimmune diabetes can be remarkably broad, ranging from diabetic ketoacidosis to the characteristics of

Latent Autoimmune Diabetes in Adults http://dx.doi.org/10.5772/intechopen.72685 29

The classification of these patients also covers a range that may seem arbitrary; for example, in the European Action LADA study, patients with GADA who started taking insulin in the first month of diagnosis were designed as classic type 1 diabetes, those who started with insulin in 6 months were not published and those who started with insulin 6 months or later were designed LADA. Compared with patients with type 2 diabetes, patients with adult onset autoimmune diabetes, even when they do not require insulin (LADA), have a lower age at the time of diabetes, lower BMI and waist/hip ratio, but a higher Pronounced loss of C-peptide

Phenotypically, patients with high GADA titres tend to have these same characteristics, but they are more marked and more similar to classic type 1 diabetes, with younger patients at the time of diagnosis being thinner with a high risk of progression to treatment with insulin. Patients with a low GADA titer are phenotypically more similar to those with DM type 2 diabetes. These differences are also observed in the metabolic syndrome, which is more frequent in type 2 diabetes than type 1 and LADA diabetes, and more prevalent in low-grade patients

Because the high GADA titer tends to be associated with multiple diabetes-associated autoantibodies (DAA), it is not surprising that the NIRAD study found that among patients with adult diabetes, more DAA were detected plus these patients needed insulin treatment and

However, there is sufficient overlap for these clinical parameters between patient groups to make it impossible to accurately distinguish autoimmune diabetes from adult type 2 diabetes

The frequency of ketoacidosis has not been documented in LADA, but it is assumed to be very low. Chronic vascular complications associated with type 1 diabetes and type 2 diabetes are

Few studies have addressed this issue. Cabrera-Rode et al. describe a lower incidence of retinopathy, nephropathy and peripheral vascular disease, in comparison with type 2 diabetics, although without significant differences given the small number of patients. Recently, a study in Korea,

in clinical characteristics only when considering individual patients [4, 54].

Given the age of onset and the frequency of this syndrome in the adult population, the coexistence of both pathologies is not infrequent. It is estimated that approximately 42% of patients may present with metabolic syndrome, a figure lower than in type 2 DM, in which the association reaches 84% [36].

It is probable that some patients present insulin resistance (IR) although the importance of this phenomenon in the onset of the disease is not clear. It has been shown that adiponectin levels are similar to individuals without DM, suggesting that IR is not part of the etiopathogenesis of the disease [46].

In turn, the presence of dyslipidemia and hypertension is higher than in type 1 diabetics [47], but less frequent than in type 2 diabetics, which could result in an intermediate cardiovascular risk between both types.

#### *5.1.3. DM type 2 and LADA*

Multiple studies have found that patients with LADA require treatment with insulin more frequently and earlier after diagnosis than those with type 2 diabetes who are negative for antibodies. GADA positivity in adult patients with diabetes who do not require insulin is associated with decreased fasting C-peptide and a decrease in peptide-C response to oral glucose [12, 18, 48, 49].

It is mentioned that, the magnitude of this insulin response is inversely related to the GADA title [18]. Curiously, insulin secretion was similar in patients recently diagnosed with LADA and DM type 2, as mentioned in two large studies conducted by Zinman et al. and Lundgren et al. [20, 50]

A metabolic study of insulin secretion and insulin sensitivity, conducted by Juhl et al. in 2014; confirmed the lack of weight difference in the groups with LADA and DM type 2 [51].

However, despite these early characteristics, over time, the increased propensity to reduce the function of b cells in LADA becomes evident [12, 18, 48].

Among GADA-positive patients, these altered metabolic parameters tend to be significantly better in those with high GADA titer compared to low GADA titer, but without a clear distinction between groups [18, 33–35].

These wide differences in metabolic parameters translate into negative GADA patients with more signs of metabolic syndrome than positive GADA patients, regardless of whether the latter have LADA or adults with diabetes onset Type 1 [34, 35, 51].

The formal examination of insulin resistance indicates that patients with LADA are more insensitive to insulin than healthy controls, but their insensitivity to insulin is comparable to or lower than that of patients with DM type 2 and is dependent on BMI [20, 40, 50, 52].
