Patients with type 1 diabetes mellitus (T1DM) may experience diabetic ketoacidosis^[1,2]. Patients with type 2 diabetes mellitus (T2DM) are likely to experience hyperglycemic non-ketotic hyperosmolar coma^[3,4]. Later microvascular complications include retinopathy^[5,6], nephropathy^[7] and peripheral and autonomic neuropathy^[8]. Macrovascular complications include coronary and peripheral atherosclerotic arterial disease. The macrovascular disease such as atherosclerosis can lead to symptomatic coronary artery disease, claudication, skin necrosis and infection^[5,9-13]. Retinopathy may progress to macular edema or proliferative retinopathy with retinal detachment or hemorrhage, which can cause blindness^[5,14]. Diabetic nephropathy develops in about one third of patients with T1DM and in a smaller percentage of those with T2DM, and can be a cause of nephrotic syndrome^[5,7]. Diabetic neuropathy is usually encountered as a polyneuropathy. Acute mononeuropathies occur more frequently in older diabetics. Autonomic neuropathy occurs primarily in diabetic patients with polyneuropathy^[5,8]. Ulcers of the feet and joint problems are important causes of morbidity in DM^[15,16]. The most important predisposing cause is the diabetic polyneuropathy. The risk of infection by fungi and bacteria has increased due to the depression of cellular immunity induced by hyperglycemia and acute circulatory deficits induced by chronic hyperglycemia^[17,18]. For all of the mentioned reasons, diabetes is a major health problem of societies, which draws interest of all disciplines of medicine. To combat these questions, there must be created multidisciplinary centers of excellence where coordinated operations on research and application of diabetes are carried out both at baseline and clinical levels^[19-21].

Principle activities should be as follows:
 • It should be established a general area to play all kinds of cooperation in science and research with national and international organizations in the field of diabetes.
 • The centers must participate in national and international scientific research in the field of diabetes and produce prestigious projects.
 • Several scientific meetings should be organized, along with other public and private institutions should be made qualified diabetes studies, participation as a partner to the studies should be guaranteed.
 • Isolation, culture and transplantation of islets of Langerhans in the experimental stage must be carried out and realized this program in clinic.
 • There should be a laboratory of stem cells for radical treatment of diabetes.
 • To be a multidisciplinary center of excellence the conditions formulated by the international diabetes must be completed.
 • To support these studies, molecular and biochemical studies and research on the beta cells and other cells of the islet of Langerhans must be carried out.
 • To investigate the immunogenetic etiopathology of T1DM should be done studies on immunology and genetics of the beta cell and should be set up projects.
 • To develop experimental models of diabetes necessary animal models must be established, these models should be standardized and scientific studies must be carried out.
 • To conclude, for essential importance of updating there should be held scientific meetings and organized post-graduate courses.

References

  The intracellular protozoan parasite Trypanosoma cruzi causes Chagas’s disease in humans^[1]. About 5 million to 8 million people are infected by T. cruzi around the world^[2]. Chagas disease has acquired global relevance because is spreading to non-endemic countries^[3], representing a significant economic global burden^[4]. The parasite infects many tissues and the presence of the parasite in peripheral neurons and heart muscle cells may be related to some of the pathological findings in the acute and chronic infection^[5]. The systemic and tissue-localized immune responses induced during the acute infection are not sufficient to eradicate the pathogen, resulting in chronic infection^[6]. Approximately 30 to 40% of the infected patients may develop megacolon, heart failure and cardiomegaly during the chronic phase of the disease, even many years after the acute infection^[1]. Yet, the majority (about 60 to 70%) of the patients that progresses to the chronic phase of the infection remains clinically healthy^[7]. Recently, results of a multicenter, double-blinded, controlled clinical trial evaluating the efficacy of a trypanocidal drug (benznidazole) to halt the disease progression concluded that this pharmacological treatment did not confer protection against disease^[8,9]. This suggests that other pathogenic mechanisms, besides the parasite itself, are involved in the progression of the disease^[5,10]. T. cruzi induces a strong immune response against its own molecular components, but the infection also induces a strong immune response to host self antigens^[10]. Therefore, a malfunction of immune regulatory mechanisms may also be involved in the autoimmune responses during the infection^[11]. In addition, the immune response to parasite antigens and host self-antigens are not dissociated and occur concomitantly^[10], and both should be considered as promoters of tissue lesion during the infection. Nevertheless, one may assume that in most of the chronically T. cruzi-infected patients, an effective but regulated immune response is achieved preventing the development of pathology^[2]. This may be due to the action of CD4+ CD25+ regulatory T cells (Tregs) that may curb the autoimmune response, allowing a partially effective anti-parasite immune response. Recent findings in humans, have shown an increased percentage of Treg cells in chagasic subjects in the indeterminate chronic phase (free of disease) when compared to patients with heart damage, suggesting an important role for Tregs in Chagas disease^[12]. Studies concerning Tregs and Chagas disease should also consider other Treg marker such as CD15s to discriminate supressors (CD15s+) versus non-suppressors (CD15s-) regulatory T cells, as the expression of this molecule could be an important prognostic biomarker for disease progression^[13]. Moreover, it has been recently demonstrated, using a nondepleting monoclonal antibody to CD25 that regulatory T cells may also help to control the adaptive immune response, during the infection in mice^[14]. The immunomodulatory activity of the nondepleting monoclonal antibody to CD25 encompassed a delayed increase of Treg frequencies and an augmented production of IL-10 by T cells that correlated with less myocardial inflammation in the chronic infection^[14]. Consequently, there is evidence that the functional activity of Treg cells might be of crucial importance during the chronic phase of the infection in decreasing tissue destruction and pathology. Therefore, the notion concerning the manipulation of Treg cells by antibodies to CD25 holds promising as a tool to treat pathological outcomes in Chagas disease. In addition, interleukin-2 (IL-2) binds to its high affinity receptor (CD25) and is also involved in the regulatory arm of the immune response by augmenting the proliferation of regulatory T cells^[15,16]. Low amounts of IL-2 favor the immunoregulatory pathway, whereas high amounts are required for driving effector immune responses^[16]. The role of IL-2 in the immunoregulatory axis of the immune system is evident in mice and humans where the availability of IL-2 was reduced^[15,16]. For instance, IL-2R-beta chain knockout mice develop autoimmune inflammatory disease and blocking of IL-2 by in vivo treatment with monoclonal antibody to IL-2 accelerates autoimmunity in mice^[17,18]. Additionally, several polymorphisms in the IL-2 pathway have been linked to type I diabetes and loss of function of Treg biological activities in human studies^[19].

Concluding Remarks
  The study of acute and chronic phases of infection with intracellular pathogens, such as T. cruzi, allows the elucidation of the mechanisms and conditions that may be targeted to reprogram the host immune system by using tools that interfere with components of the regulatory arm of the immune system machinery, thus providing new strategies to treat Chagas disease, besides the use of drugs that only kills the parasite in vivo, sterilizing the host. In this regard, the in vivo biological activity of nondepleting antibodies to CD25 seems to reinforce rather than inhibit the function of regulatory T cells in mice and humans^[14,20]. Additionally, new approaches, including in vivo administration of IL-2 or complexes of IL-2/anti-IL-2 to increase the numbers and functional activity of regulatory T cells are also desired^[16,21]. However, it should be noted that more studies, using different strains of T. cruzi in combination with distinct strains of mice should be performed in order to better establish this conceptual clinical intervention.

Acknowledgement:
  This work was supported by PAPES/CNPq/FIOCRUZ and Fundação Octacílio Gualberto, Faculdade de Medicina de Petropolis (FMP-FASE). The authors declare that there are no conflicts of interests. We thanks Vinicius Mota for critical review of the manuscript.

References