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Article ; Online: What does the licensing of teplizumab mean for diabetes care?

Quinn, Lauren M / Swaby, Rabbi / Tatovic, Danijela / Narendran, Parth / Besser, Rachel E J / Dayan, Colin M

2023 Volume 25, Issue 8, Page(s) 2051–2057

MeSH term(s)	Humans ; Diabetes Mellitus, Type 1/drug therapy ; Hypoglycemic Agents/adverse effects ; Antibodies, Monoclonal, Humanized/therapeutic use ; Autoantibodies
Chemical Substances	teplizumab (S4M959U2IJ) ; Hypoglycemic Agents ; Antibodies, Monoclonal, Humanized ; Autoantibodies
Language	English
Publishing date	2023-04-24
Publishing country	England
Document type	Journal Article
ZDB-ID	1454944-x
ISSN	1463-1326 ; 1462-8902
ISSN (online)	1463-1326
ISSN	1462-8902
DOI	10.1111/dom.15071
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Zs.A 5442: Show issues

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Article ; Online: Additional insulin dosing for fat and protein in children with type 1 diabetes using multiple daily injections.

Frohock, Anne Marie / Oke, Jason / Yaliwal, Chandan / Edge, Julie / Besser, Rachel E J

Pediatric diabetes

2022 Volume 23, Issue 6, Page(s) 742–748

Abstract: Objective: High-fat high-protein (HFHP) meals are associated with post-prandial hyperglycemia in type 1 diabetes (T1D), administration of additional insulin for such meals is recommended in order to optimize glucose levels. Optimal timing of additional ... ...

Abstract	Objective: High-fat high-protein (HFHP) meals are associated with post-prandial hyperglycemia in type 1 diabetes (T1D), administration of additional insulin for such meals is recommended in order to optimize glucose levels. Optimal timing of additional insulin for HFHP meals in children and young people receiving multiple daily injections (MDI) remains unclear. Aim: To investigate the glycemic impact of additional insulin doses given before or after eating a HFHP meal in children with T1D using MDI. Research design and methods: A randomized, controlled three period crossover trial of 27 participants aged 13 years (6.1-17.7) at two Pediatric Diabetes centers was conducted. Additional rapid-acting insulin for the fat-protein content of a standardized HFHP meal was given at three time points Results: There was no difference in post-prandial glucose parameters when additional HFHP insulin was administered at Conclusion: We found no benefit in giving additional insulin as a split dose for HFHP meals in children using MDI, mild hypoglycemia was common. Future studies would benefit from refinement of the insulin dose algorithm.
MeSH term(s)	Adolescent ; Blood Glucose/metabolism ; Blood Glucose Self-Monitoring ; Child ; Diabetes Mellitus, Type 1/drug therapy ; Diabetes Mellitus, Type 1/metabolism ; Humans ; Hypoglycemia ; Hypoglycemic Agents/therapeutic use ; Insulin ; Insulin Infusion Systems/adverse effects ; Meals ; Postprandial Period
Chemical Substances	Blood Glucose ; Hypoglycemic Agents ; Insulin
Language	English
Publishing date	2022-06-14
Publishing country	Denmark
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1502504-4
ISSN	1399-5448 ; 1745-1426 ; 1399-543X
ISSN (online)	1399-5448
ISSN	1745-1426 ; 1399-543X
DOI	10.1111/pedi.13372
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Zs.A 5422: Show issues

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Article: Determination of C-peptide in children: when is it useful?

Besser, Rachel E J

Pediatric endocrinology reviews : PER

2013 Volume 10, Issue 4, Page(s) 494–502

Abstract: Diabetes results from insulin deficiency but despite this endogenous insulin secretion is infrequently measured. C-peptide is not present in synthetic insulin so it's presence indicates endogenous secretion. One of the key roles for measuring C-peptide ... ...

Abstract	Diabetes results from insulin deficiency but despite this endogenous insulin secretion is infrequently measured. C-peptide is not present in synthetic insulin so it's presence indicates endogenous secretion. One of the key roles for measuring C-peptide in childhood is to assist in the diagnosis of diabetes subtypes, which in turn determines appropriate management. It is also useful in Type 1 diabetes to monitor disease course, both in clinical practice and in trials following intervention with disease modifying agents. Measuring C-peptide routinely in Type 1 diabetes provides valuable information to the patient and clinician about glucose variability, risk of hypoglycemia and ketoacidosis. Newer more practical methods of C-peptide determination are now available to allow assessment of endogenous insulin secretion in routine clinical practice. We review the physiology of insulin secretion, the essential roles and methods for C-peptide determination in blood and in urine.
MeSH term(s)	Adolescent ; Biomarkers/blood ; Biomarkers/urine ; C-Peptide/blood ; C-Peptide/urine ; Child ; Diabetes Mellitus, Type 1/diagnosis ; Diabetes Mellitus, Type 1/metabolism ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/metabolism ; Humans ; Proinsulin/metabolism
Chemical Substances	Biomarkers ; C-Peptide ; Proinsulin (9035-68-1)
Language	English
Publishing date	2013-07
Publishing country	Israel
Document type	Journal Article ; Review
ZDB-ID	2434390-0
ISSN	1565-4753
ISSN	1565-4753
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Zs.A 6700: Show issues

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Article ; Online: Diagnosing Type 1 diabetes in adults: Guidance from the UK T1D Immunotherapy consortium.

Tatovic, Danijela / Jones, Angus G / Evans, Carol / Long, Anna E / Gillespie, Kathleen / Besser, Rachel E J / Leslie, Richard David / Dayan, Colin M

Diabetic medicine : a journal of the British Diabetic Association

2022 Volume 39, Issue 7, Page(s) e14862

MeSH term(s)	Adult ; Diabetes Mellitus, Type 1/diagnosis ; Diabetes Mellitus, Type 1/therapy ; Diabetes Mellitus, Type 2 ; Genetic Predisposition to Disease ; Humans ; Immunotherapy ; United Kingdom/epidemiology
Language	English
Publishing date	2022-05-06
Publishing country	England
Document type	Letter
ZDB-ID	605769-x
ISSN	1464-5491 ; 0742-3071 ; 1466-5468
ISSN (online)	1464-5491
ISSN	0742-3071 ; 1466-5468
DOI	10.1111/dme.14862
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Zs.A 1954: Show issues

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Article ; Online: Diabetic Ketoacidosis at Onset of Type 1 Diabetes and Glycemic Outcomes with Closed-Loop Insulin Delivery.

Lakshman, Rama / Najami, Mazin / Allen, Janet M / Ware, Julia / Wilinska, Malgorzata E / Hartnell, Sara / Thankamony, Ajay / Randell, Tabitha / Ghatak, Atrayee / Besser, Rachel E J / Elleri, Daniela / Trevelyan, Nicola / Campbell, Fiona M / Hovorka, Roman / Boughton, Charlotte K

Diabetes technology & therapeutics

2024 Volume 26, Issue 3, Page(s) 198–202

Abstract: The presence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) is associated with higher glycated hemoglobin levels over time. We evaluated whether hybrid-closed loop (HCL) therapy from onset of T1D could prevent the adverse impact of ... ...

Abstract	The presence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) is associated with higher glycated hemoglobin levels over time. We evaluated whether hybrid-closed loop (HCL) therapy from onset of T1D could prevent the adverse impact of DKA at diagnosis on long-term glycemic outcomes. This was a posthoc analysis from 51 adolescents using HCL from diagnosis of T1D as part of the CLOuD trial (NCT02871089). We compared glycemic and insulin metrics between adolescents with (
MeSH term(s)	Adolescent ; Humans ; Insulin/therapeutic use ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/drug therapy ; Diabetic Ketoacidosis/etiology ; Blood Glucose ; Insulin Infusion Systems ; Insulin, Regular, Human
Chemical Substances	Insulin ; Blood Glucose ; Insulin, Regular, Human
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1452816-2
ISSN	1557-8593 ; 1520-9156
ISSN (online)	1557-8593
ISSN	1520-9156
DOI	10.1089/dia.2023.0307
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Zs.A 5269: Show issues

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Article ; Online: Clinical care advice for monitoring of islet autoantibody positive individuals with presymptomatic type 1 diabetes.

Hendriks, A Emile J / Marcovecchio, M Loredana / Besser, Rachel E J / Bonifacio, Ezio / Casteels, Kristina / Elding Larsson, Helena / Gemulla, Gita / Lundgren, Markus / Kordonouri, Olga / Mallone, Roberto / Pociot, Flemming / Szypowska, Agnieszka / Toppari, Jorma / Berge, Thekla von dem / Ziegler, Anette G / Mathieu, Chantal / Achenbach, Peter

Diabetes/metabolism research and reviews

2024 Volume 40, Issue 2, Page(s) e3777

Abstract: Background/aim: Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta-cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to ... ...

Abstract	Background/aim: Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta-cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to identify autoantibody-positive individuals increases, a rise in presymptomatic type 1 diabetes individuals seeking medical attention is expected. Current guidance on how to monitor these individuals in a safe but minimally invasive way is limited. This article aims to provide clinical guidance for monitoring individuals with presymptomatic type 1 diabetes to reduce the risk of diabetic ketoacidosis (DKA) at diagnosis. Methods: Expert consensus was obtained from members of the Fr1da, GPPAD, and INNODIA consortia, three European diabetes research groups. The guidance covers both specialist and primary care follow-up strategies. Results: The guidance outlines recommended monitoring approaches based on age, disease stage and clinical setting. Individuals with presymptomatic type 1 diabetes are best followed up in specialist care. For stage 1, biannual assessments of random plasma glucose and HbA1c are suggested for children, while annual assessments are recommended for adolescents and adults. For stage 2, 3-monthly clinic visits with additional home monitoring are advised. The value of repeat OGTT in stage 1 and the use of continuous glucose monitoring in stage 2 are discussed. Primary care is encouraged to monitor individuals who decline specialist care, following the guidance presented. Conclusions: As type 1 diabetes screening programs become more prevalent, effective monitoring strategies are essential to mitigate the risk of complications such as DKA. This guidance serves as a valuable resource for clinicians, providing practical recommendations tailored to an individual's age and disease stage, both within specialist and primary care settings.
MeSH term(s)	Child ; Adolescent ; Adult ; Humans ; Diabetes Mellitus, Type 1 ; Autoantibodies ; Blood Glucose Self-Monitoring ; Blood Glucose ; Diabetic Ketoacidosis
Chemical Substances	Autoantibodies ; Blood Glucose
Language	English
Publishing date	2024-02-20
Publishing country	England
Document type	Journal Article
ZDB-ID	1470192-3
ISSN	1520-7560 ; 1520-7552
ISSN (online)	1520-7560
ISSN	1520-7552
DOI	10.1002/dmrr.3777
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Zs.A 2119: Show issues

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Article ; Online: Early-childhood body mass index and its association with the COVID-19 pandemic, containment measures and islet autoimmunity in children with increased risk for type 1 diabetes.

Hummel, Sandra / Rosenberger, Sarah / von dem Berge, Thekla / Besser, Rachel E J / Casteels, Kristina / Hommel, Angela / Kordonouri, Olga / Elding Larsson, Helena / Lundgren, Markus / Marcus, Benjamin A / Oltarzewski, Mariusz / Rochtus, Anne / Szypowska, Agnieszka / Todd, John A / Weiss, Andreas / Winkler, Christiane / Bonifacio, Ezio / Ziegler, Anette-G

Diabetologia

2024 Volume 67, Issue 4, Page(s) 670–678

Abstract: Aims/hypothesis: The aim of this study was to determine whether BMI in early childhood was affected by the COVID-19 pandemic and containment measures, and whether it was associated with the risk for islet autoimmunity.: Methods: Between February 2018 ...

Abstract	Aims/hypothesis: The aim of this study was to determine whether BMI in early childhood was affected by the COVID-19 pandemic and containment measures, and whether it was associated with the risk for islet autoimmunity. Methods: Between February 2018 and May 2023, data on BMI and islet autoimmunity were collected from 1050 children enrolled in the Primary Oral Insulin Trial, aged from 4.0 months to 5.5 years of age. The start of the COVID-19 pandemic was defined as 18 March 2020, and a stringency index was used to assess the stringency of containment measures. Islet autoimmunity was defined as either the development of persistent confirmed multiple islet autoantibodies, or the development of one or more islet autoantibodies and type 1 diabetes. Multivariate linear mixed-effect, linear and logistic regression methods were applied to assess the effect of the COVID-19 pandemic and the stringency index on early-childhood BMI measurements (BMI as a time-varying variable, BMI at 9 months of age and overweight risk at 9 months of age), and Cox proportional hazard models were used to assess the effect of BMI measurements on islet autoimmunity risk. Results: The COVID-19 pandemic was associated with increased time-varying BMI (β = 0.39; 95% CI 0.30, 0.47) and overweight risk at 9 months (β = 0.44; 95% CI 0.03, 0.84). During the COVID-19 pandemic, a higher stringency index was positively associated with time-varying BMI (β = 0.02; 95% CI 0.00, 0.04 per 10 units increase), BMI at 9 months (β = 0.13; 95% CI 0.01, 0.25) and overweight risk at 9 months (β = 0.23; 95% CI 0.03, 0.43). A higher age-corrected BMI and overweight risk at 9 months were associated with increased risk for developing islet autoimmunity up to 5.5 years of age (HR 1.16; 95% CI 1.01, 1.32 and HR 1.68, 95% CI 1.00, 2.82, respectively). Conclusions/interpretation: Early-childhood BMI increased during the COVID-19 pandemic, and was influenced by the level of restrictions during the pandemic. Controlling for the COVID-19 pandemic, elevated BMI during early childhood was associated with increased risk for childhood islet autoimmunity in children with genetic susceptibility to type 1 diabetes.
MeSH term(s)	Humans ; Child, Preschool ; Diabetes Mellitus, Type 1 ; Autoimmunity/genetics ; Body Mass Index ; Pandemics ; Islets of Langerhans ; Overweight/complications ; COVID-19/epidemiology ; COVID-19/complications ; Autoantibodies
Chemical Substances	Autoantibodies
Language	English
Publishing date	2024-01-12
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-023-06079-z
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Article ; Online: Transdermal Blood Sampling for C-Peptide Is a Minimally Invasive, Reliable Alternative to Venous Sampling in Children and Adults With Type 1 Diabetes.

Besser, Rachel E J / Long, Anna E / Owen, Katharine R / Law, Rebecca / Birks, Jacqueline S / Pearce, Olivia / Williams, Claire L / Scudder, Claire L / McDonald, Timothy J / Todd, John A

Diabetes care

2023 Volume 47, Issue 2, Page(s) 239–245

Abstract: Objective: C-peptide and islet autoantibodies are key type 1 diabetes biomarkers, typically requiring venous sampling, which limits their utility. We assessed transdermal capillary blood (TCB) collection as a practical alternative.: Research design ... ...

Abstract	Objective: C-peptide and islet autoantibodies are key type 1 diabetes biomarkers, typically requiring venous sampling, which limits their utility. We assessed transdermal capillary blood (TCB) collection as a practical alternative. Research design and methods: Ninety-one individuals (71 with type 1 diabetes, 20 control; individuals with type 1 diabetes: aged median 14.8 years [interquartile range (IQR) 9.1-17.1], diabetes duration 4.0 years [1.5-7.7]; control individuals: 42.2 years [38.0-52.1]) underwent contemporaneous venous and TCB sampling for measurement of plasma C-peptide. Participants with type 1 diabetes also provided venous serum and plasma, and TCB plasma for measurement of autoantibodies to glutamate decarboxylase, islet antigen-2, and zinc transporter 8. The ability of TCB plasma to detect significant endogenous insulin secretion (venous C-peptide ≥200 pmol/L) was compared along with agreement in levels, using Bland-Altman. Venous serum was compared with venous and TCB plasma for detection of autoantibodies, using established thresholds. Acceptability was assessed by age-appropriate questionnaire. Results: Transdermal sampling took a mean of 2.35 min (SD 1.49). Median sample volume was 50 µL (IQR 40-50) with 3 of 91 (3.3%) failures, and 13 of 88 (14.7%) <35 µL. TCB C-peptide showed good agreement with venous plasma (mean venous ln[C-peptide] - TCB ln[C-peptide] = 0.008, 95% CI [-0.23, 0.29], with 100% [36 of 36] sensitivity/100% [50 of 50] specificity to detect venous C-peptide ≥200 pmol/L). Where venous serum in multiple autoantibody positive TCB plasma agreed in 22 of 32 (sensitivity 69%), comparative specificity was 35 of 36 (97%). TCB was preferred to venous sampling (type 1 diabetes: 63% vs. 7%; 30% undecided). Conclusions: Transdermal capillary testing for C-peptide is a sensitive, specific, and acceptable alternative to venous sampling; TCB sampling for islet autoantibodies needs further assessment.
MeSH term(s)	Adult ; Child ; Humans ; Aged ; Diabetes Mellitus, Type 1 ; C-Peptide ; Autoantibodies ; Blood Specimen Collection ; Biomarkers ; Glutamate Decarboxylase
Chemical Substances	C-Peptide ; Autoantibodies ; Biomarkers ; Glutamate Decarboxylase (EC 4.1.1.15)
Language	English
Publishing date	2023-12-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc23-1379
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Zs.A 1434: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Closed-Loop from Diagnosis of Type 1 Diabetes in Children and Young People.

Ghatak, Atrayee / Boughton, Charlotte K / Allen, Janet M / Ware, Julia / Wilinska, Malgorzata E / Hartnell, Sara / Thankamony, Ajay / Randell, Tabitha / Besser, Rachel E J / Elleri, Daniela / Trevelyan, Nicola / Campbell, Fiona M / Hovorka, Roman

Diabetes technology & therapeutics

2023 Volume 25, Issue 9, Page(s) 673–674

MeSH term(s)	Child ; Humans ; Adolescent ; Diabetes Mellitus, Type 1/diagnosis ; Diabetes Mellitus, Type 1/drug therapy ; Hypoglycemic Agents/therapeutic use ; Hypoglycemia ; Insulin Infusion Systems ; Insulin/therapeutic use ; Blood Glucose ; Cross-Over Studies
Chemical Substances	Hypoglycemic Agents ; Insulin ; Blood Glucose
Language	English
Publishing date	2023-07-12
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	1452816-2
ISSN	1557-8593 ; 1520-9156
ISSN (online)	1557-8593
ISSN	1520-9156
DOI	10.1089/dia.2023.0217
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Article ; Online: Exploring C-peptide loss in type 1 diabetes using growth curve analysis.

Besser, Rachel E J / Ludvigsson, Johnny / Hindmarsh, Peter C / Cole, Tim J

PloS one

2018 Volume 13, Issue 7, Page(s) e0199635

Abstract: Objectives: C-peptide (CP) loss in type 1 diabetes (T1D) is highly variable, and factors influencing it are poorly understood. We modelled CP values in T1D patients from diagnosis for up to 6 years, treating the serial data as growth curves plotted ... ...

Abstract	Objectives: C-peptide (CP) loss in type 1 diabetes (T1D) is highly variable, and factors influencing it are poorly understood. We modelled CP values in T1D patients from diagnosis for up to 6 years, treating the serial data as growth curves plotted against time since diagnosis. The aims were to summarise the pattern of CP loss (i.e. growth curve shape) in individual patients in simple terms, and to identify baseline characteristics that predict this pattern in individuals. Materials and methods: Between 1976 and 2011, 442 T1D patients initially aged <18y underwent 120-minute mixed meal tolerance tests (MMTT) to calculate area under the curve (AUC) CP, at 3, 9, 18, 30, 48 and 72 months after diagnosis (n = 1537). The data were analysed using the novel SITAR mixed effects growth curve model (SuperImposition by Translation And Rotation). It fits a mean AUC growth curve, but also allows the curve's mean level and rate of fall to vary between individuals so as to best fit the individual patient curves. These curve adjustments define individual curve shape. Results: The square root (√) AUC scale provided the best fit. The mean levels and rates of fall for individuals were normally distributed and uncorrelated with each other. Age at diagnosis and √AUC at 3 months strongly predicted the patient-specific mean levels, while younger age at diagnosis (p<0.0001) and the 120-minute CP value of the 3-month MMTT (p = 0.002) predicted the patient-specific rates of fall. Conclusions: SITAR growth curve analysis is a useful tool to assess CP loss in type 1 diabetes, explaining patient differences in terms of their mean level and rate of fall. A definition of rapid CP loss could be based on a quantile of the rate of fall distribution, allowing better understanding of factors determining CP loss and stratification of patients into targeted therapies.
MeSH term(s)	Adolescent ; Area Under Curve ; Biomarkers ; C-Peptide/blood ; C-Peptide/deficiency ; Cell Count ; Child ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/diagnosis ; Female ; Humans ; Insulin-Secreting Cells/metabolism ; Male
Chemical Substances	Biomarkers ; C-Peptide
Language	English
Publishing date	2018-07-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0199635
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