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

2020 ◽  
Vol 21 (6) ◽  
pp. 2103 ◽  
Author(s):  
Novella Rapini ◽  
Riccardo Schiaffini ◽  
Alessandra Fierabracci
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Early Stage ◽  
Β Cell ◽  
Good Glycemic Control ◽  
Autoimmune Attack ◽  
Β Cell Function ◽  
Microvascular And Macrovascular Complications

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.

scholarly journals Residual β-Cell Function More than Glycemic Control Determines Abnormalities of the Insulin-Like Growth Factor System in Type 1 Diabetes

2004 ◽  
Vol 89 (12) ◽  
pp. 6305-6309 ◽  
Author(s):  
Christina A. Hedman ◽  
Jan Frystyk ◽  
Torbjörn Lindström ◽  
Jian-Wen Chen ◽  
Allan Flyvbjerg ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Cell Function ◽  
Β Cell ◽  
Good Glycemic Control ◽  
C Peptide ◽  
Igf I ◽  
Β Cell Function ◽  
Igfbp 3

Abstract The GH-IGF-I axis is disturbed in patients with type 1 diabetes. Our aim was to investigate whether abnormalities are found in patients in very good glycemic control and, if so, to estimate the role of residual β-cell function. Patients with hemoglobin A1c (HbA1c) less than 6% (reference range, 3.6–5.4%) were selected for the study. Twenty-two men and 24 women, aged 41.3 ± 13.8 yr (mean ± sd), with a diabetes duration of 17.8 ± 14.6 yr participated. Healthy controls (15 women and nine men), aged 41.3 ± 13.0 yr, were also studied. Overnight fasting serum samples were analyzed for HbA1c, C peptide, free and total IGFs, IGF-binding proteins (IGFBPs), GH-binding protein, and IGFBP-3 proteolysis. HbA1c was 5.6 ± 0.5% in patients and 4.4 ± 0.3% in controls. Total IGF-I was 148 ± 7 μg/liter in patients and 178 ± 9 μg/liter in controls (P < 0.001). Free IGF-I, total IGF-II, IGFBP-3, and GH-binding protein were lower, whereas IGFBP-1, IGFBP-1-bound IGF-I, and IGFBP-2 were elevated compared with control values. Patients with detectable C peptide (≥100 pmol/liter) had higher levels of total IGF-I, free IGF-I, and total IGF-II and lower levels of IGFBP-1 and IGFBP-2 than those with an undetectable C peptide level despite having identical average HbA1c. IGFBP-3 proteolysis did not differ between patients and controls. Despite very good glycemic control, patients with type 1 diabetes and no endogenous insulin production have low free and total IGF-I. Residual β-cell function, therefore, seems more important for the disturbances in the IGF system than good metabolic control per se, suggesting that portal insulin delivery is needed to normalize the IGF system.

scholarly journals Case Report: Markedly Long-Term Preservation of Pancreatic β‐Cell Function in a Subject With Elderly Onset of Type 1 Diabetes Mellitus Showing High-Titer Autoimmune Antibodies for Over 4 Years

2021 ◽  
Vol 12 ◽  
Author(s):  
Ryo Shigemoto ◽  
Takatoshi Anno ◽  
Fumiko Kawasaki ◽  
Kohei Kaku ◽  
Hideaki Kaneto
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Cell Function ◽  
Β Cell ◽  
Cell Destruction ◽  
Β Cell Function ◽  
Long Term Preservation

Type 1 diabetes mellitus (T1DM) is mainly triggered by autoimmune β-cell destruction, usually leading to absolute insulin deficiency. Regarding the speed of β-cell destruction, there are large variations depending on age. In some adult cases, sufficient β-cell function is sometimes retained for a relatively long period and eventually they become dependent on insulin for survival. It is known that even in subjects with T1DM showing high titers of such antibodies, insulin secretory capacity is preserved under several conditions such as “honeymoon” period and slowly progressive T1DM (SPIDDM). Herein, we reported the acute onset T1DM subject with long-term preservation of β-cell function, although his anti-GAD antibody and anti-IA-2 antibody titers were very high for more than 4 years. This case is very important in that his β-cell function was preserved with dipeptidyl peptidase-4 inhibitor alone. This means that there are large variations in the speed of β-cell destruction in the onset of T1DM.

scholarly journals Residual β cell function in long-term type 1 diabetes associates with reduced incidence of hypoglycemia

2021 ◽  
Vol 131 (3) ◽  
Author(s):  
Rose A. Gubitosi-Klug ◽  
Barbara H. Braffett ◽  
Susan Hitt ◽  
Valerie Arends ◽  
Diane Uschner ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Β Cell ◽  
Β Cell Function ◽  
Term Type

scholarly journals Updates on Immune Therapies in Type 1 Diabetes

2016 ◽  
Vol 12 (2) ◽  
pp. 89 ◽  
Author(s):  
Bimota Nambam ◽  
◽  
Michael J Haller ◽  
Keyword(s):  
Clinical Trials ◽  
Type 1 Diabetes ◽  
Cell Function ◽  
Β Cell ◽  
Immune Therapies ◽  
Β Cell Function ◽  
Potential Benefits ◽  
New Onset

Multiple clinical trials investigating the efficacy and safety of immunotherapeutic interventions in new onset type 1 diabetes (T1D) have failed to yield long term clinical benefit. Lack of efficacy has frequently been attributed to an incomplete understanding of the pathways involved in T1D and the use of single immunotherapeutic agents. Recent mechanistic studies have improved our knowledge of the complex etiopathogenesis of T1D. This in turn has provided the framework for new and ongoing clinical trials in new onset T1D patients and at-risk subjects. Focus has also shifted towards the potential benefits of synergistic combinatorial approaches, both in terms of efficacy and the potential for reduced side effects. These efforts seek to develop intervention strategies that will preserve β-cell function, and ultimately prevent and reverse clinical disease.

The severity of clinical presentation of type 1 diabetes in children does not significantly influence the pattern of residual β-cell function and long-term metabolic control

2003 ◽  
Vol 4 (1) ◽  
pp. 4-9 ◽  
Author(s):  
Silvana Salardi ◽  
Stefano Zucchini ◽  
Alessandro Cicognani ◽  
Elena Corbelli ◽  
Roberta Santoni ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Metabolic Control ◽  
Clinical Presentation ◽  
Cell Function ◽  
Β Cell ◽  
Β Cell Function

Association of T-cell reactivity with β-cell function in recent onset type 1 diabetes patients

2010 ◽  
Vol 34 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Christian Pfleger ◽  
Guido Meierhoff ◽  
Hubert Kolb ◽  
Nanette C. Schloot
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Cell Function ◽  
Β Cell ◽  
Cell Reactivity ◽  
Recent Onset ◽  
Onset Type ◽  
Β Cell Function ◽  
T Cell Reactivity

scholarly journals Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes

2018 ◽  
Vol 128 (8) ◽  
pp. 3460-3474 ◽  
Author(s):  
Lorraine Yeo ◽  
Alyssa Woodwyk ◽  
Sanjana Sood ◽  
Anna Lorenc ◽  
Martin Eichmann ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Effector Memory ◽  
Β Cell ◽  
Β Cell Function ◽  
Memory Differentiation

scholarly journals Residual β-cell function after 10 years of autoimmune type 1 diabetes: prevalence, possible determinants, and implications for metabolism

2021 ◽  
Vol 9 (8) ◽  
pp. 650-650
Author(s):  
Jin Cheng ◽  
Min Yin ◽  
Xiaohan Tang ◽  
Xiang Yan ◽  
Yuting Xie ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Diabetes Prevalence ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Systemic TNFα correlates with residual β-cell function in children and adolescents newly diagnosed with type 1 diabetes

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Anne Julie Overgaard ◽  
Jens Otto Broby Madsen ◽  
Flemming Pociot ◽  
Jesper Johannesen ◽  
Joachim Størling
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Disease Onset ◽  
Newly Diagnosed ◽  
Β Cell ◽  
Entire Study ◽  
C Peptide ◽  
Disease Remission ◽  
Β Cell Function

Abstract Background Type 1 diabetes (T1D) is caused by immune-mediated destruction of the β-cells. After initiation of insulin therapy many patients experience a period of improved residual β-cell function leading to partial disease remission. Cytokines are important immune-modulatory molecules and contribute to β-cell damage in T1D. The patterns of systemic circulating cytokines during T1D remission are not clear but may constitute biomarkers of disease status and progression. In this study, we investigated if the plasma levels of various pro- and anti-inflammatory cytokines around time of diagnosis were predictors of remission and residual β-cell function in children with T1D followed for one year after disease onset. Methods In a cohort of 63 newly diagnosed children (33% females) with T1D with a mean age of 11.3 years (3.3–17.7), ten cytokines were measured of which eight were detectable in plasma samples by Mesoscale Discovery multiplex technology at study start and after 6 and 12 months. Linear regression models were used to evaluate association of cytokines with stimulated C-peptide. Results Systemic levels of tumor necrosis factor (TNF)-α, interleukin (IL)-2 and IL-6 inversely correlated with stimulated C-peptide levels over the entire study (P < 0.05). The concentrations of TNFα and IL-10 at study start predicted stimulated C-peptide level at 6 months (P = 0.011 and P = 0.043, respectively, adjusted for sex, age, HbA1c and stage of puberty). Conclusions In recent-onset T1D, systemic cytokine levels, and in particular that of TNFα, correlate with residual β-cell function and may serve as prognostic biomarkers of disease remission and progression to optimize treatment strategies. Trial Registration The study was performed according to the criteria of the Helsinki II Declaration and was approved by the Danish Capital Region Ethics Committee on Biomedical Research Ethics (journal number H-3-2014-052). The parents of all participants gave written consent.

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