Interview: Disease-specific therapeutic interventions in Type 1 diabetes

2013 ◽  
Vol 3 (5) ◽  
pp. 363-365
Author(s):  
Pere Santamaria
Keyword(s):  
Type 1 Diabetes ◽  
Therapeutic Interventions ◽  
Disease Specific

scholarly journals Detecting Insulitis in Type 1 Diabetes with Ultrasound Phase-change Contrast Agents

2020 ◽  
Author(s):  
David G. Ramirez ◽  
Awaneesh K. Upadhyay ◽  
Vinh T. Pham ◽  
Mark Ciccaglione ◽  
Mark A Borden ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Contrast Agents ◽  
Cell Mass ◽  
Nod Mice ◽  
Therapeutic Interventions ◽  
Β Cells ◽  
Β Cell ◽  
Diabetes Onset ◽  
Ultrasound Contrast

AbstractType 1 diabetes (T1D) results from immune infiltration and destruction of insulin-producing β-cells within the pancreatic islets of Langerhans (insulitis), resulting in loss of glucose homeostasis. Early diagnosis during pre-symptomatic T1D would allow for therapeutic intervention prior to substantial loss of β-cell mass at T1D onset. There are limited methods to track the progression of insulitis and β-cell mass decline in pre-symptomatic T1D. During insulitis, the islet microvasculature increases permeability, such that sub-micron sized particles can extravasate and accumulate within the islet microenvironment. Ultrasound is a widely deployable and cost-effective clinical imaging modality. However, conventional microbubble contrast agents are restricted to the vasculature. Sub-micron sized nanodroplet (ND) phasechange agents can be vaporized into micron-sized bubbles; serving as a circulating microbubble precursor. We tested if NDs extravasate into the immune-infiltrated islet microenvironment. We performed ultrasound contrast-imaging following ND infusion in NOD mice and NOD;Rag1ko controls, and tracked diabetes development. We measured the biodistribution of fluorescently labeled NDs, with histological analysis of insulitis. Ultrasound contrast signal was elevated in the pancreas of 10w NOD mice following ND infusion and vaporization, but was absent in both the non-infiltrated kidney of NOD mice and pancreas of Rag1ko controls. High contrast elevation also correlated with rapid diabetes onset. In pancreata of NOD mice, infiltrated islets and nearby exocrine tissue were selectively labeled with fluorescent NDs. Thus, contrast ultrasound imaging with ND phase-change agents can detect insulitis prior to diabetes onset. This will be important for monitoring disease progression to guide and assess preventative therapeutic interventions for T1D.SignificanceThere is a need for imaging methods to detect type1 diabetes (T1D) progression prior to clinical diagnosis. T1D is a chronic disease that results from autoreactive T cells infiltrating the islet of Langerhans and destroying insulin-producing β-cells. Overt disease takes years to present and is only diagnosed after significant β-cells loss. As such, the possibility of therapeutic intervention to preserve β-cell mass is hampered by an inability to follow pre-symptomatic T1D progression. There are immunotherapies that can delay T1D development. However identifying ‘at risk’ individuals, and tracking whether therapeutic interventions are impacting disease progression, prior to T1D onset, is lacking. A method to detect insulitis and β-cell mass decline would present an opportunity to guide therapeutic treatments to prevent T1D.

scholarly journals An Examination of Sex Differences in a Disease-Specific Model of Disordered Eating Behaviors in Type 1 Diabetes

2019 ◽  
Vol 45 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Laura B Smith ◽  
Nicole Foster ◽  
Sureka Bollepalli ◽  
Hannah F Fitterman-Harris ◽  
Diana Rancourt
Keyword(s):  
Risk Factors ◽  
Type 1 Diabetes ◽  
Eating Disorder ◽  
Disordered Eating ◽  
Eating Behaviors ◽  
Eating Disorder Risk ◽  
Disordered Eating Behaviors ◽  
Disease Specific ◽  
Disorder Risk

Abstract Objective Preliminary evidence supports the integration of type 1 diabetes (T1D) disease-specific factors into eating disorder risk models. The current study explored whether cross-sectional associations among constructs included in the modified dual pathway model of eating disorder risk for individuals with T1D are similar across sex among adolescents and young adults with T1D. Methods Original study participants were recruited from the T1D Exchange Clinic Network, a U.S. registry of individuals with T1D. Online surveys included measures of general eating disorder risk factors, hypothesized T1D-specific risk factors, and a T1D-specific eating disorder questionnaire. The current study is a secondary analysis with the adolescents (13–17 years; n = 307; 46.9% female) and young adults (18–25 years; n = 313; 62.6% female) from the original sample. In the absence of strong measurement invariance for all measures of interest, sex-specific path models were estimated among the adolescent and young adult cohorts. Results Only two paths emerged as significant in the female, but not male, adolescent model. In the young adult cohort, all significant paths were the same across sex. Conclusions Both general and T1D-specific risk factors are associated with disordered eating behaviors in the T1D population. Patterns of associations were similar across male and female youth with T1D, suggesting that sex-specific prevention approaches to disordered eating behaviors among T1D youth may not be warranted.

scholarly journals Islet expression of type I interferon response sensors is associated with immune infiltration and viral infection in type 1 diabetes

2021 ◽  
Vol 7 (9) ◽  
pp. eabd6527
Author(s):  
Paola S. Apaolaza ◽  
Diana Balcacean ◽  
Jose Zapardiel-Gonzalo ◽  
Grace Nelson ◽  
Nataliya Lenchik ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Therapeutic Interventions ◽  
Interferon Response ◽  
Type I ◽  
Persistent Infections ◽  
Secretion Pathway ◽  
B Cell Function ◽  
Microbial Stress

Previous results indicate the presence of an interferon (IFN) signature in type 1 diabetes (T1D), capable of inducing chronic inflammation and compromising b cell function. Here, we determined the expression of the IFN response markers MxA, PKR, and HLA-I in the islets of autoantibody-positive and T1D donors. We found that these markers can be coexpressed in the same islet, are more abundant in insulin-containing islets, are highly expressed in islets with insulitis, and their expression levels are correlated with the presence of the enteroviral protein VP1. The expression of these markers was associated with down-regulation of multiple genes in the insulin secretion pathway. The coexistence of an IFN response and a microbial stress response is likely to prime islets for immune destruction. This study highlights the importance of therapeutic interventions aimed at eliminating potentially persistent infections and diminishing inflammation in individuals with T1D.

scholarly journals Acute Versus Progressive Onset of Diabetes in NOD Mice: Potential Implications for Therapeutic Interventions in Type 1 Diabetes

Diabetes ◽  
2015 ◽  
Vol 64 (11) ◽  
pp. 3885-3890 ◽  
Author(s):  
Clayton E. Mathews ◽  
Song Xue ◽  
Amanda Posgai ◽  
Yaima L. Lightfoot ◽  
Xia Li ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Nod Mice ◽  
Therapeutic Interventions ◽  
Onset Of Diabetes

scholarly journals Two to Tango: Dialogue between Adaptive and Innate Immunity in Type 1 Diabetes

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Lin Sun ◽  
Shugang Xi ◽  
Guangyu He ◽  
Zhuo Li ◽  
Xiaokun Gang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
Type 1 Diabetes ◽  
Autoimmune Disorder ◽  
Innate Immune ◽  
Therapeutic Interventions ◽  
T Cell Subsets ◽  
And Function

Type 1 diabetes mellitus (T1DM) is a long-term and chronic autoimmune disorder, in which the immune system attacks the pancreatic β-cells. Both adaptive and innate immune systems are involved in T1DM development. Both B-cells and T-cells, including CD4+ and CD8+ T-cells, as well as other T-cell subsets, could affect onset of autoimmunity. Furthermore, cells involved in innate immunity, including the macrophages, dendritic cells, and natural killer (NK) cells, could also accelerate or decelerate T1DM development. In this review, the crosstalk and function of immune cells in the pathogenesis of T1DM, as well as the corresponding therapeutic interventions, are discussed.

scholarly journals Disease-specific biases in alternative splicing and tissue-specific dysregulation revealed by multitissue profiling of lymphocyte gene expression in type 1 diabetes

2017 ◽  
Vol 27 (11) ◽  
pp. 1807-1815 ◽  
Author(s):  
Jeremy R.B. Newman ◽  
Ana Conesa ◽  
Matthew Mika ◽  
Felicia N. New ◽  
Suna Onengut-Gumuscu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 1 Diabetes ◽  
Alternative Splicing ◽  
Tissue Specific ◽  
Disease Specific

The Relationship of Control-Related Beliefs to Depressive Symptomatology Among Children With Type 1 Diabetes and Asthma: A Disease-Specific Approach

2005 ◽  
Vol 34 (4) ◽  
pp. 261-272 ◽  
Author(s):  
Ahna L. Hoff ◽  
Larry L. Mullins ◽  
Melanie C. Page ◽  
Melissa Y. Carpentier ◽  
John M. Chaney ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Depressive Symptomatology ◽  
Specific Approach ◽  
Relationship Of ◽  
The Relationship ◽  
Disease Specific
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