**6. Clinical features**

Multiple studies on MetS and its relationship with DM type LADA estimate that at least 30%

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 associa-

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 etiopatho-

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 cardiovascu-

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

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

A metabolic study of insulin secretion and insulin sensitivity, conducted by Juhl et al. in 2014;

However, despite these early characteristics, over time, the increased propensity to reduce the

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 dis-

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

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].

confirmed the lack of weight difference in the groups with LADA and DM type 2 [51].

function of b cells in LADA becomes evident [12, 18, 48].

latter have LADA or adults with diabetes onset Type 1 [34, 35, 51].

tinction between groups [18, 33–35].

of patients diagnosed with type LADA have metabolic disorders [36].

tion reaches 84% [36].

28 Diabetes and Its Complications

genesis of the disease [46].

lar risk between both types.

*5.1.3. DM type 2 and LADA*

glucose [12, 18, 48, 49].

et al. [20, 50]

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 diabetes that can be controlled only with diet.

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

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

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 had an earlier age [53].

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