Timing of Immunotherapy in Type 1 Diabetes: The Earlier, the Better?

Felton, Jamie L.

doi:10.4049/immunohorizons.2000105

Cited by 5 publications

(4 citation statements)

References 63 publications

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“…Based on the significantly increased understanding of the complex immunopathogenesis related to human T1DM (Richardson & Pugliese, 2021 ), immune therapy exhibits great potential in treating or preventing T1DM (Smigoc Schweiger, 2022 ). Immune therapy for T1DM has shifted from immunosuppression to tolerance induction as a result of potential side effects or risks related to immunosuppression, particularly among younger children (Felton, 2021 ). For tolerance induction in T1DM, oral immunization has been an attractive and simple route of drug administration.…”

Section: Discussionmentioning

confidence: 99%

Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice

et al. 2023

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Induction of oral tolerance by vaccination with type 1 diabetes mellitus (T1DM)-associated autoantigens exhibits great potential in preventing and treating this autoimmune disease. However, antigen degradation in the gastrointestinal tract (GIT) limits the delivery efficiency of oral antigens. Previously, bacterium-like particles (BLPs) have been used to deliver a single-chain insulin (SCI-59) analog (BLPs-SCI-59) or the intracellular domain of insulinoma-associated protein 2 (IA-2ic) (BLPs-IA-2ic). Both monovalent BLPs vaccines can suppress T1DM in NOD mice by stimulating the corresponding antigen-specific oral tolerance, respectively. Here, we constructed two bivalent BLPs vaccines which simultaneously deliver SCI-59 and IA-2ic (Bivalent vaccine-mix or Bivalent vaccine-SA), and evaluated whether there is an additive beneficial effect on tolerance induction and suppression of T1DM by treatment with BLPs-delivered bi-autoantigens. Compared to the monovalent BLPs vaccines, oral administration of the Bivalent vaccine-mix could significantly reduce morbidity and mortality in T1DM. Treatment with the bivalent BLPs vaccines (especially Bivalent vaccine-mix) endowed the mice with a stronger ability to regulate blood glucose and protect the integrity and function of pancreatic islets than the monovalent BLPs vaccines treatment. This additive effect of BLPs-delivered bi-autoantigens on T1DM prevention may be related to that SCI-59- and IA-2-specific Th2-like immune responses could be induced, which was more beneficial for the correction of Th1/Th2 imbalance. In addition, more CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) were induced by treatment with the bivalent BLPs vaccines than did the monovalent BLPs vaccines. Therefore, multiple autoantigens delivered by BLPs maybe a promising strategy to prevent T1DM by efficiently inducing antigen-specific immune tolerance.

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Section: Discussionmentioning

confidence: 99%

Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice

et al. 2023

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“…However, lower insulin requirements may also have been due to enhanced RBCF protection and resultant higher endogenous insulin production in the Intervention Group. As in several past interventional therapy studies, (24,27) patients with new-onset T1D in this sample were recruited while they still had sufficient RBCF to enable preservation. In prior studies, fasting C-peptide concentrations >0.5ng/mL were deemed sufficiently high upon enrollment.…”

Section: ❚ Discussionmentioning

confidence: 99%

Combination therapy with lansoprazole and cholecalciferol is associated with a slower decline in residual beta-cell function and lower insulin requirements in children with recent onset type 1 diabetes: results of a pilot study

Reddy¹,

Dayal²,

Sachdeva³

et al. 2022

Einstein (São Paulo)

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Objective: To investigate the effects of combination therapy with cholecalciferol and lansoprazole on residual β-cell function and glycemic control in children with new-onset type 1 diabetes. Methods: Children aged 6-12 years with type 1 diabetes were allocated to receive cholecalciferol and lansoprazole (Group 1) or no treatment (Group 2). Children were maintained on their respective insulin regimens and kept records of blood sugar and insulin doses taken. Children were followed at three-month intervals for six months. Changes in mean fasting C-peptide and HbA1c levels, daily insulin doses, fasting blood glucose and mean blood glucose levels from baseline to end of the study were analyzed. Results: Twenty-eight children (14 per group) met the eligibility criteria. Fasting C-peptide levels decreased significantly from baseline to study end in both groups (mean decrease -0.19±0.09ng/mL and -0.28±0.08ng/mL, p=0.04 and p=0.001; Group 1 and Group 2 respectively). However, fasting C-peptide level drop was significantly smaller in Group 1 compared to Group 2 (30.6% and 47.5% respectively; p=0.001). Likewise, daily insulin doses decreased significantly in both groups (-0.59±0.14units/kg and -0.37±0.24units/kg respectively; p=0.001). All patients recruited completed the study. No adverse events were reported. Conclusion: Combined therapy with cholecalciferol and lansoprazole for six months was associated with smaller decline in residual β-cell function and lower insulin requirements in children with new-onset type 1 diabetes. Preliminary findings of this small-scale study need to be confirmed by larger studies. Registry of Clinical Trials: (www.ctri.nic.in) under number REF/2021/03/041415 N.

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“…Life 2023, 13, 1663 2 of 24 Novel strategies for preventing and managing T1DM are investigated [8,9]. One research direction in this field is antigen vaccination (with oral insulin or peptides) and stemcell-based replacement therapies [10] to prevent and reverse diabetes autoimmunity.…”

Section: Introductionmentioning

confidence: 99%

“…Novel strategies for preventing and managing T1DM are investigated [8,9]. One re search direction in this field is antigen vaccination (with oral insulin or peptides) and stem-cell-based replacement therapies [10] to prevent and reverse diabetes autoimmunity FDA approved in November 2022 the first drug-Tzield (teplizumab-mzwv) injectionthat can delay the onset of T1DM [11][12][13], resulting in years of disease remission [14].…”

Section: Introductionmentioning

confidence: 99%

Current Technologies for Managing Type 1 Diabetes Mellitus and Their Impact on Quality of Life—A Narrative Review

Elian,

Popovici,

Ozon

et al. 2023

Life

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Type 1 diabetes mellitus is a chronic autoimmune disease that affects millions of people and generates high healthcare costs due to frequent complications when inappropriately managed. Our paper aimed to review the latest technologies used in T1DM management for better glycemic control and their impact on daily life for people with diabetes. Continuous glucose monitoring systems provide a better understanding of daily glycemic variations for children and adults and can be easily used. These systems diminish diabetes distress and improve diabetes control by decreasing hypoglycemia. Continuous subcutaneous insulin infusions have proven their benefits in selected patients. There is a tendency to use more complex systems, such as hybrid closed-loop systems that can modulate insulin infusion based on glycemic readings and artificial intelligence-based algorithms. It can help people manage the burdens associated with T1DM management, such as fear of hypoglycemia, exercising, and long-term complications. The future is promising and aims to develop more complex ways of automated control of glycemic levels to diminish the distress of individuals living with diabetes.

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Timing of Immunotherapy in Type 1 Diabetes: The Earlier, the Better?

Cited by 5 publications

References 63 publications

Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice

Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice

Combination therapy with lansoprazole and cholecalciferol is associated with a slower decline in residual beta-cell function and lower insulin requirements in children with recent onset type 1 diabetes: results of a pilot study

Current Technologies for Managing Type 1 Diabetes Mellitus and Their Impact on Quality of Life—A Narrative Review

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