Immunotherapy Strategies for the Prevention and Treatment of Distinct Stages of Type 1 Diabetes: An Overview

Abstract

Type 1 diabetes mellitus is a heterogeneous disorder characterized by destruction of pancreatic β cells, culminating in absolute insulin deficiency. The goals of Type 1 diabetes care, established by the Diabetes Control and Complications Trial (DCCT), are to achieve good glycemic control, to prevent hyperglycaemia (which is associated with long-term microvascular and macrovascular complications) and to avoid recurrent episodes of hypoglycaemia (which may have adverse effects on cognitive function). However, despite continuing optimization of insulin therapy regimes, the actual hormonal substitutive administration acts only to treat the symptoms without an effect on disease pathology and etiopathogenesis. In recent decades, a great deal of interest has been focused on prevention approaches in high-risk individuals, based on the hypothesis that a therapeutic intervention, if applied at the early stage of disease, might contribute to maintaining endogenous β cell function by preserving the residual β cell reservoir from autoimmune attack. This manuscript provides an overview of the most important immunotherapeutic interventions established so far for Type 1 diabetes treatment at different stages of disease that have reached an advanced stage of assessment.

Guidance for high-dose vitamin D supplementation for prolonging the honeymoon phase in children and adolescents with new-onset type 1 diabetes

“…Our RCT is also the longest investigation in PR in an exclusively pediatric population receiving standardized insulin regimen and high dose ergocalciferol. The dose of ergocalciferol used in this study was similar to the dose used in other studies that suggested that higher doses of vitamin D are necessary for the detection of its extra skeletal functions (11,16). The patients' characteristics and the RCT design make the results of the study generalizable to all youth with newly diagnosed T1D given the ethnic and racial diversity, the age range, and the duration of the trial.…”

“…These include several side effects such as headache, nausea, decreased white blood cell count, and severe rashes. Previous studies that used lower doses of vitamin D had reported unclear results on vitamin D's impact on PR (8,15), thus suggesting that high-dose vitamin D may be necessary to detect vitamin D's extra-skeletal effects in humans (11,16) as has been reported in animal studies (17). Pozzilli and co-workers (18) hypothesized that vitamin D has immunomodulatory functions that favor Th2 immune response that could protect residual b-cells from further destruction following the diagnosis of T1D.…”

“…Several attempts have been made in the past few decades to prolong the duration of the honeymoon phase (11). Recent attempts using immunomodulatory and immunosuppressive agents to stop the destruction of b-cells have shown some promise, but the protection is short-lived and insufficient (11)(12)(13)(14). For example, Teplizumab, an anti-CD3 monoclonal antibody, appears to act on the preclinical phase of T1D by reducing b-cell inflammation, however, its pharmacodynamic properties preclude its widespread acceptability (12).…”

“…Prolonging the duration of PR improves glycemic control and reduces long-term complications of T1D ( 7 – 10 ). Several attempts have been made in the past few decades to prolong the duration of the honeymoon phase ( 11 ). Recent attempts using immunomodulatory and immunosuppressive agents to stop the destruction of β-cells have shown some promise, but the protection is short-lived and insufficient ( 11 – 14 ).…”

Improvement of Lipoplexes With a Sialic Acid Mimetic to Target the C1858T PTPN22 Variant for Immunotherapy in Endocrine Autoimmunity

“…On a general ground the approach based on the use of functionalized lipoplexes we need to remark that this is a personalized gene therapy approach of specific immunocytes. This should avoid side effects of general immunosuppression encountered in trials with MAbs immunotherapeutic approaches such as anti-CD3 ( 49 , 50 ).…”