Assessing generalizability of a new-onset type 1 diabetes Biobank

Background and Hypothesis: Type 1 diabetes (T1D) is characterized by insulin deficiency due to autoimmune pancreatic beta cell destruction. The Wells Center Pediatric Diabetes Research Program is collecting blood and urine samples from children with new onset T1D admitted to Riley Hospital. These samples are being used to discover biomarkers predictive of disease heterogeneity and course. Since not every newly-diagnosed child enrolls in the Biobank, we examined if persons enrolled are similar or different from the at-large population of newly-diagnosed children to know how generalizable samples collected are from our newly-diagnosed population. Project Methods: Between September 2016 and May 2018, 71 newly-diagnosed children (mean age 9.6±4.3 years) and their caregivers were approached by researchers and asked to provide blood/urine samples. Thirty-four consented/assented (as required); 21 had blood and urine collected; 13 urine only. We looked for differences in age, sex, race, BMI, socioeconomic status (based on zip code), and admission bloodwork parameters between participants and non-participants. Results: Overall, participants were more likely to be white and have higher admission bicarbonate. Children who provided blood and urine had no other significant differences from non-participants. Children who provided urine only were more likely to be male and to have higher admission bicarbonate than non-participants. Currently, we are obtaining data to make comparisons with the general population of all patients diagnosed at Riley. Conclusion/Potential Impact: Our Biobank will provide samples to explore novel biomarkers to facilitate highly-targeted therapies and to screen future preventative treatments. As we continue to collect data, it will remain important to monitor and carefully consider its generalizability.

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Qualitative study of barriers to clinical trial retention in adults with recently diagnosed type 1 diabetes

BMJ Open ◽

10.1136/bmjopen-2018-022353 ◽

2018 ◽

Vol 8 (7) ◽

pp. e022353 ◽

Cited By ~ 1

Author(s):

Catherine Henshall ◽

Parth Narendran ◽

Robert C Andrews ◽

Amanda Daley ◽

Keith A Stokes ◽

...

Keyword(s):

Clinical Trials ◽

Type 1 Diabetes ◽

Qualitative Study ◽

Qualitative Methodology ◽

Cell Function ◽

Retention Rates ◽

Newly Diagnosed ◽

Advance Study ◽

New Onset

ObjectivesRegular physical exercise may preserve β cell function in newly diagnosed adults with type 1 diabetes (T1D). However, clinical trials to test this theory require the recruitment and retention of adults with new-onset T1D, which can be challenging. We sought to determine the overall experiences of newly diagnosed adults with T1D in an exercise study, to understand issues that influence the retention of trial participants in such studies.DesignQualitative methodology using individual face-to-face (n=6) and telephone interviews (n=14). Interview transcripts were thematically analysed using the framework method.SettingThe study took place at five participating UK hospitals.ParticipantsTwenty participants, aged 19–55 years, in the Exercise for Type 1 Diabetes study were interviewed to explore their study experiences and identify motivators and deterrents towards the study. Participants in control and intervention arms were interviewed, as were people with T1D who had completed (n=16) and withdrawn (n=4).ResultsParticipants revealed barriers and facilitators to retention; the majority were generalisable to clinical trials of people with newly diagnosed T1D. Coming to terms with a diagnosis of T1D, lack of time, work pressures, level of health professional support, volume, clarity and consistency of information and feedback and a desire for knowledge about their condition were all cited as influencing factors to trial retention.ConclusionsTo our knowledge, this is the first qualitative study to examine the experience of being involved in an exercise trial by people with T1D. Findings suggest appointments could be shorter, available outside of working hours and planned longer in advance; study information should be clear, consistent and in electronic and paper formats; questionnaires need minimising; healthcare support and feedback needs providing regularly; thought is required around how to support non-exercising arm participants. These considerations may improve participant retention rates in new-onset T1D studies.

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CDE Perspectives of Providing New-Onset Type 1 Diabetes Education Using Formal Vignettes and Simulation

The Diabetes Educator ◽

10.1177/0145721716676893 ◽

2016 ◽

Vol 43 (1) ◽

pp. 97-104 ◽

Cited By ~ 2

Author(s):

Neesha Ramchandani ◽

Kim Johnson ◽

Karen Cullen ◽

Terri Hamm ◽

Jean Bisordi ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetes Management ◽

Qualitative Content Analysis ◽

Patient Simulation ◽

Human Patient Simulation ◽

Newly Diagnosed ◽

Human Patient ◽

Diabetes Educators ◽

New Onset

Purpose The purpose of this article is to describe the 4 Parent Education Through Simulation-Diabetes (PETS-D) nurse certified diabetes educators’ (CDEs) perspectives of teaching parents of children with newly diagnosed type 1 diabetes mellitus (T1DM) early diabetes management skills using formal vignettes and a human patient simulator/human patient simulation (HPS) to augment/enhance the teaching–learning process. Methods A qualitative descriptive approach was used. Four CDEs were interviewed by phone about their teaching experiences. Meticulous notes were taken. Data were analyzed using qualitative content analysis. Results The vignettes (and use of HPS) provided structure, especially for parents who were struggling to learn. Certified diabetes educators described a short learning curve to master the use of the HPS manikin. Human patient simulation-enhanced education was described as helpful for teaching multiple caregivers about diabetes. Certified diabetes educators also described factors that affect parent learning, mechanical issues with the HPS, and additional space requirements for HPS-enhanced education. Conclusion Vignettes and HPS-enhanced education can successfully be used to educate parents of children with new-onset T1DM and were preferred by the CDEs when compared with previous teaching strategies. The results of this study support the use of both vignette-based and HPS-enhanced education when a child is newly diagnosed with T1DM. Further studies need to be done to see if these effects persist with different populations, during different stages of the disease, and for individuals with other chronic illnesses.

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Circulating Levels of MicroRNA from Children with Newly Diagnosed Type 1 Diabetes and Healthy Controls: Evidence That miR-25 Associates to Residual Beta-Cell Function and Glycaemic Control during Disease Progression

Experimental Diabetes Research ◽

10.1155/2012/896362 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 44

Author(s):

Lotte B. Nielsen ◽

Cheng Wang ◽

Kaspar Sørensen ◽

Claus H. Bang-Berthelsen ◽

Lars Hansen ◽

...

Keyword(s):

Type 1 Diabetes ◽

Glycaemic Control ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Control Group ◽

Healthy Controls ◽

Newly Diagnosed ◽

New Onset

This study aims to identify key miRNAs in circulation, which predict ongoing beta-cell destruction and regeneration in children with newly diagnosed Type 1 Diabetes (T1D). We compared expression level of sera miRNAs from new onset T1D children and age-matched healthy controls and related the miRNAs expression levels to beta-cell function and glycaemic control. Global miRNA sequencing analyses were performed on sera pools from two T1D cohorts (n= 275 and 129, resp.) and one control group (n= 151). We identified twelve upregulated human miRNAs in T1D patients (miR-152, miR-30a-5p, miR-181a, miR-24, miR-148a, miR-210, miR-27a, miR-29a, miR-26a, miR-27b, miR-25, miR-200a); several of these miRNAs were linked to apoptosis and beta-cell networks. Furthermore, we identified miR-25 as negatively associated with residual beta-cell function (est.: −0.12,P= 0.0037), and positively associated with glycaemic control (HbA1c) (est.: 0.11,P= 0.0035) 3 months after onset. In conclusion this study demonstrates that miR-25 might be a “tissue-specific” miRNA for glycaemic control 3 months after diagnosis in new onset T1D children and therefore supports the role of circulating miRNAs as predictive biomarkers for tissue physiopathology and potential intervention targets.

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Cognitive Function following Diabetic Ketoacidosis in Children with New Onset or Previously Diagnosed Type 1 Diabetes

10.2337/figshare.12824396 ◽

2020 ◽

Author(s):

Simona Ghetti ◽

Nathan Kuppermann ◽

Arleta Rewers ◽

Sage R. Myers ◽

Jeff E. Schunk ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Ketoacidosis ◽

Hemoglobin A1c ◽

Economic Status ◽

Digit Span ◽

Diabetes Diagnosis ◽

Newly Diagnosed ◽

Neurocognitive Assessment ◽

New Onset

Objective. This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes, and whether the same is true in children who had been previously diagnosed after accounting for variations in glycemic control and other relevant factors. Design. We prospectively enrolled 758 children, 6- to 18-years-old, who presented with DKA in a randomized multi-site clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled. Results. Among all patients, moderate/severe DKA was associated with lower IQ (β=-.12, p<0.001), item-color recall (β=-0.08, p=0.010), and forward digit span (β=-0.06, p=0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β=-0.08, p=0.04). Among previously diagnosed patients, repeated DKA exposure and higher hemoglobin A1c were independently associated with lower IQ (β=-.10 and β=-0.09, respectively, ps <.01) and higher hemoglobin A1c was associated with lower item-color recall (β=-0.10, p=0.007), after accounting for hypoglycemia, diabetes duration, and socio-economic status. Conclusion. A single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.

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Teamwork, Targets, Technology, and Tight Control in Newly Diagnosed Type 1 Diabetes: Pilot 4T Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab859 ◽

2021 ◽

Author(s):

Priya Prahalad ◽

Victoria Y Ding ◽

Dessi P Zaharieva ◽

Ananta Addala ◽

Ramesh Johari ◽

...

Keyword(s):

Type 1 Diabetes ◽

Glucose Monitoring ◽

Newly Diagnosed ◽

Tight Control ◽

Target Setting ◽

Multivariable Regression ◽

Historic Cohort ◽

Hba1c Levels ◽

New Onset

Abstract Context Youth with type 1 diabetes (T1D) do not meet hemoglobin A1c (HbA1c) targets. Objective To assess HbA1c outcomes in children with new onset T1D enrolled in the Teamwork, Targets, Technology and Tight Control (4T) Study. Method HbA1c levels were compared between the 4T and Historical cohorts. HbA1c differences between cohorts were estimated using locally estimated scatter plot smoothing (LOESS). The change from nadir HbA1c (month 4) to 12 months post-diagnosis was estimated by cohort using a piecewise mixed effects regression model accounting for age at diagnosis, sex, ethnicity, and insurance type. Setting and Participants We recruited 135 youth with newly diagnosed T1D at Stanford Children’s Health. Intervention Starting July 2018, all youth within the first month of T1D diagnosis were offered continuous glucose monitoring (CGM) initiation and remote CGM data review was added in March 2019. Main Outcome Measure HbA1c. Results HbA1c at 6, 9, and 12 months post-diagnosis was lower in the 4T cohort than in the Historic cohort (-0.54%, -0.52%, and -0.58%, respectively). Within the 4T cohort, HbA1c at 6, 9, and 12 months post-diagnosis was lower in those patients with Remote Monitoring than those without (-0.14%, -0.18%, -0.14%, respectively). Multivariable regression analysis showed that the 4T cohort experienced a significantly lower increase in HbA1c between months 4 and 12 (p < 0.001). Conclusions A technology-enabled team-based approach to intensified new onset education involving target setting, CGM initiation, and remote data review significantly decreased HbA1c in youth with T1D 12 months post-diagnosis.

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Cognitive Function following Diabetic Ketoacidosis in Children with New Onset or Previously Diagnosed Type 1 Diabetes

10.2337/figshare.12824396.v1 ◽

2020 ◽

Author(s):

Simona Ghetti ◽

Nathan Kuppermann ◽

Arleta Rewers ◽

Sage R. Myers ◽

Jeff E. Schunk ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Ketoacidosis ◽

Hemoglobin A1c ◽

Economic Status ◽

Digit Span ◽

Diabetes Diagnosis ◽

Newly Diagnosed ◽

Neurocognitive Assessment ◽

New Onset

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Mediators and mechanisms of pancreatic beta-cell death in type 1 diabetes

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302008000200003 ◽

2008 ◽

Vol 52 (2) ◽

pp. 156-165 ◽

Cited By ~ 84

Author(s):

Pierre Pirot ◽

Alessandra K. Cardozo ◽

Décio L. Eizirik

Keyword(s):

Type 1 Diabetes ◽

Beta Cell ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Map Kinases ◽

Pancreatic Beta Cell ◽

Insulin Deficiency ◽

Beta Cell Destruction ◽

Pro Inflammatory Cytokines

Type 1 diabetes mellitus (T1D) is characterized by severe insulin deficiency resulting from chronic and progressive destruction of pancreatic beta-cells by the immune system. The triggering of autoimmunity against the beta-cells is probably caused by environmental agent(s) acting in the context of a predisposing genetic background. Once activated, the immune cells invade the islets and mediate their deleterious effects on beta-cells via mechanisms such as Fas/FasL, perforin/granzyme, reactive oxygen and nitrogen species and pro-inflammatory cytokines. Binding of cytokines to their receptors on the beta-cells activates MAP-kinases and the transcription factors STAT-1 and NFkappa-B, provoking functional impairment, endoplasmic reticulum stress and ultimately apoptosis. This review discusses the potential mediators and mechanisms leading to beta-cell destruction in T1D.

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Anti-SARS-CoV-2 antibodies in new-onset type 1 diabetes in children during pandemic in Belgium

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0289 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Anissa Messaaoui ◽

Lucia Hajselova ◽

Sylvie Tenoutasse

Keyword(s):

Type 1 Diabetes ◽

Base Excess ◽

Newly Diagnosed ◽

Onset Type ◽

Two Samples ◽

Long Term Consequences ◽

Mean Time ◽

New Onset

Abstract Objectives Questions are emerging concerning the long-term consequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, as a possible increase in type 1 diabetes. This study aims to describe the prevalence of anti-SARS-CoV-2 antibodies in children developing type 1 diabetes during this pandemic in Belgium. Methods This observational study included children and adolescents (under 16 years) admitted with new-onset type 1 diabetes. SARS-CoV-2 serology was taken within the first month of diabetes. Results Of the 75 participants, anti-SARS-CoV-2 antibodies were positive in 20% of patients. They had an increased bicarbonate and base excess at diagnosis. Overall 29% of patients presented diabetic ketoacidosis at diagnosis and 9% of them were positive for anti-SARS-CoV-2 antibodies. Insulinoma-associated protein 2 antibodies positivity had significantly higher frequencies in children without anti-SARS-CoV-2 antibodies (49 (81%) vs. 5 (33%), p=0.038). Nine (15%) patients, initially seronegative, have developed anti-SARS-CoV-2 antibodies between the two samples (mean time 8 ± 4 weeks). Conclusions The prevalence of anti-SARS-CoV-2 antibodies in children with newly diagnosed type 1 diabetes (20%) is similar to that found in children without diabetes in Belgium, a country severely affected by this pandemic.

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T Cell Epitopes and Neo-epitopes in Type 1 Diabetes: A Comprehensive Update and Reappraisal

10.2337/figshare.12179796 ◽

2020 ◽

Author(s):

Ada Admin ◽

Eddie A. James ◽

Roberto Mallone ◽

Sally C. Kent ◽

Teresa P. DiLorenzo

Keyword(s):

Type 1 Diabetes ◽

T Cell ◽

Beta Cell ◽

Pancreatic Beta Cell ◽

Hla Class I ◽

Diabetes Research ◽

T Cell Epitopes ◽

Online Appendix ◽

Cell Monitoring

The autoimmune disease type 1 diabetes is characterized by effector T cell responses to pancreatic beta cell-derived peptides presented by HLA class I and class II molecules, leading ultimately to beta cell demise and insulin insufficiency. Although a given HLA molecule presents a vast array of peptides, only those recognized by T cells are designated as epitopes. Given their intimate link to etiology, the discovery and characterization of T cell epitopes is a critical aspect of type 1 diabetes research. Understanding epitope recognition is also crucial for the pursuit of antigen-specific immunotherapies and implementation of strategies for T cell monitoring. For these reasons, a cataloging and appraisal of the T cell epitopes targeted in type 1 diabetes was completed over a decade ago, providing an important resource for both the research and the clinical communities. Here we present a much-needed update and reappraisal of this earlier work, and include an online appendix that cross-indexes each epitope with its primary references and Immune Epitope Database (IEDB) identifier. Our analysis includes a grading scale to score the degree of evidence available for each epitope, which conveys our perspective on several useful criteria for epitope evaluation. While providing an efficient summary of the arguably impressive current state of knowledge, this work also brings to light several deficiencies. These include the need for improved epitope validation, as few epitopes score highly by the criteria employed, and the dearth of investigations of the epitopes recognized in the context of several under-studied type 1 diabetes-associated HLA molecules.

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Leptin in Children with Newly Diagnosed Type 1 Diabetes: Effect of Insulin Therapy

International Journal of Experimental Diabetes Research ◽

10.1155/edr.2001.121 ◽

2001 ◽

Vol 2 (2) ◽

pp. 121-127 ◽

Cited By ~ 6

Author(s):

Kenneth L. McCormick ◽

Gail J. Mick ◽

Lisa Butterfield ◽

Hugh Ross ◽

Elaine Parton ◽

...

Keyword(s):

Type 1 Diabetes ◽

Insulin Therapy ◽

Serum Insulin ◽

Insulin Dose ◽

Newly Diagnosed ◽

Baseline Serum ◽

Serum Leptin ◽

Onset Type ◽

New Onset

Leptin, the gene product of adipose tissue that signals caloric plentitudeviacentral nervous system receptors, may also have diverse peripheral metabolic actions. Of paramount interest has been the potential interaction(s) between leptin and insulin. Insofar as insulin alters leptin secretion/action (orvice versa), dysregulation of this system could contribute to disease states such as diabetes.The purpose of this study was to examine the effect of exogenous insulin on serum leptin in children with newly-diagnosed Type 1 diabetes. Since these patients are hypoinsulinemic (insulindeplet. ed) at diagnosis, they present an ideal opportunity to examine the effect of insulin repletion on serum leptin. Seventeen patients were enrolled. At baseline (prior to insulin therapy), leptin levels were 4.3 ± 1.1ng/ml; they were not statistically related to the baseline serum insulin or illness severity. There was no significant change in serum leptin before, shortly (1–6 days) or several weeks (3–26 weeks) after insulin treatment even when the data was corrected for changes in BMI, hemoglobinA1C, and daily insulin dose. Since repletion of the insulin deficiency that is present in non-acidotic, ambulatory patients with new onset Type 1 diabetes did not alter serum leptin, these results argue against an effect of insulin on serum leptin in the absence of the acute diabetic ketoacidosis. Because as the recuperative months following the diagnosis of new onset Type 1 diabetes are marked by weight gain, the absence of a rise in serum leptin might also indicate either an adaptive (weight permissive) or pathologic (impaired secretory) deficit.

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