**9. Conclusions**

**8.3. Glitazones**

32 Diabetes and Its Complications

LADA [2, 70, 71].

endogenous insulin production [72].

with LADA treated only with insulin) [76, 77].

position these therapies as the choice.

patients), concludes that:

therapy.

of the β cell mass [2, 70].

Theoretically they could have their value in the treatment, not only to improve the sensitivity of the insulin but also to exert an anti-inflammatory effect that would favor the preservation

There is interesting evidence that glitazones increase insulin synthesis and the insulin content

Zhou and others have demonstrated the efficacy of treatment with rosiglitazone in combination with insulin, which helps preserve the function of the cell compared to insulin alone in

Sitagliptin is a potent DPP-4 inhibitor which results in the delay of degradation of incretin hormones (glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP)), thereby improving beta-cell function and resulting in better glycemic control in patients with T2D.

Recent studies demonstrate that the use of sitagliptin in individuals with T1D improved overall the glycemic control and reduced insulin requirements without altering the amount of

A prospective study of 1-year duration demonstrated maintenance of beta-cell function through the administration of sitagliptin in patients with recent-onset LADA [73]. A similar study proved that c-peptide secretion and glycemic control was improved by the use of another DPP-4 inhibitor, saxagliptin, versus placebo in LADA patients [74, 75]. All these accumulating evidences support the hypothesis that this may be a class effect; however, further studies are required.

A clinical trial showed that insulin therapy was the best treatment in this type of diabetic, and that the use of glibenclamide produced a persistence of the ICA (the ICA persisted in 100% of the subjects with LADA treated with glibenclamide + insulin), and that its exclusion decreased the presence of these antibodies (the ICA disappeared in 75% of the individuals

The use of glibenclamide or another sulphonylurea is not recommended in the treatment of these patients or their combination with insulin [65, 66], since it could contribute to the persistence of the autoimmune process and the probable progressive destruction of pancreatic cells. Finally, a meta-analysis on pharmacological treatment [71], with a total of 8 publications (735

• There are no benefits in the metabolic control when associating hypoglycemics with insulin

• Preservation of initial C peptide with early insulin therapy or rosiglitazone, which would

of islet cells as well as improve the secretory response of islets [71].

**8.4. Potential strategies for preventing b-cell destruction in LADA**

• Better metabolic control with insulin compared to sulfonylureas. • Insulin dependence earlier in patients treated with sulfonylureas.

#### **9.1. Summary: knowledge and uncertainty**

Patients with DM type LADA are more likely to have lower C-peptide, associated with fewer signs of metabolic syndrome; higher levels of HbA1c, faster progress to insulin therapy. It is not yet clear how DM type LADA is associated with the loss of insulin secretion capacity.

#### **9.2. Summary: knowledge and uncertainty**

There are no clear clinical features that distinguish autoimmune diabetes from type 2 diabetes. However, there is a tendency for adult patients with GADA, even when they do not require insulin, being younger at the time of diagnosis and thinner with a greater tendency to progress to treatment with insulin. Within a cohort of positive GADA adult patients, the GADA title and the number of LADA patients impact the clinical and biochemical differences of type 2 diabetes. The clinical phenotype should drive the management strategy.
