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Article ; Online: The Relationship Between Glycated Hemoglobin and Time in Range in a Pediatric Population.

Vandenbempt, Mathilde / Matheussen, Hanne / Charleer, Sara / Rochtus, Anne / Casteels, Kristina

2024 Volume 26, Issue 5, Page(s) 346–350

Abstract: In adults with type 1 diabetes (T1D), time in range (TIR) [70-180 mg/dL] has been proposed as an additional metric besides glycated hemoglobin (HbA1c). This retrospective monocentric cohort study determined the correlation between HbA1c and TIR during ... ...

Abstract	In adults with type 1 diabetes (T1D), time in range (TIR) [70-180 mg/dL] has been proposed as an additional metric besides glycated hemoglobin (HbA1c). This retrospective monocentric cohort study determined the correlation between HbA1c and TIR during the 2, 4, and 12 weeks (TIR
MeSH term(s)	Humans ; Glycated Hemoglobin/analysis ; Retrospective Studies ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/drug therapy ; Diabetes Mellitus, Type 1/complications ; Female ; Male ; Child ; Blood Glucose/analysis ; Adolescent ; Blood Glucose Self-Monitoring ; Glycemic Control/statistics & numerical data ; Child, Preschool ; Time Factors ; Hypoglycemic Agents/therapeutic use
Chemical Substances	Glycated Hemoglobin ; Blood Glucose ; hemoglobin A1c protein, human ; Hypoglycemic Agents
Language	English
Publishing date	2024-01-04
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.2023.0482
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Zs.A 5269: Show issues

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Book: 1,25-dihydroxyvitamin D 3 and its analogues as immunomodulators in autoimmune type 1 diabetes

Casteels, Kristina

mechanisms of action and preclinical applications

(Acta biomedica lovaniensia ; 167)

1998

Author's details	Kristina Casteels
Series title	Acta biomedica lovaniensia ; 167 Acta biomedica Lovaniensia
Collection	Acta biomedica Lovaniensia
Language	English
Size	150 S. : Ill., graph. Darst.
Publisher	Leuven Univ. Press
Publishing place	Leuven
Publishing country	Belgium
Document type	Book
HBZ-ID	HT013360196
ISBN	90-6186-876-9 ; 978-90-6186-876-7
Database	Catalogue ZB MED Medicine, Health

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2002 A 2715	order for loan	Magazin

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Article ; Online: Pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome: A case series.

Jacobs, An / Cifelli, Paramita / Delbeck, Daniel / Elbarbary, Nancy / Gevers, Evelien / Sumnik, Zdenek / Amaratunga, Shenali / Pundziute-Lyckå, Auste / Casteels, Kristina

Hormone research in paediatrics

2024

Abstract: Introduction: Pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID) syndrome is a rare disease, and part of the cluster Histiocytosis-lymphadenopathy plus syndrome (H syndrome), which is associated with mutations in the SLC29A3 gene. ... ...

Abstract	Introduction: Pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID) syndrome is a rare disease, and part of the cluster Histiocytosis-lymphadenopathy plus syndrome (H syndrome), which is associated with mutations in the SLC29A3 gene. Patients with PHID show clinical features of H syndrome, but also have insulin-dependent diabetes mellitus. The PHID associated diabetes has previously been described as predominantly in absence of pancreatic autoantibodies. Case Series Presentation: Through an open call in two international diabetes registers, clinical and genetic characteristics of 7 PHID patients in 6 treatment centres were collected after informed consent. All of them had consanguinity in their families, and their origins were located in North-African and Middle Eastern regions. 4 out of 7 patients had at least one positive pancreatic autoantibody. Discussion and conclusion: Our case series reveals that PHID exhibits a wide range of clinical symptoms and signs. When consanguinity is present in a patient with newly diagnosed diabetes, and/or if other atypical symptoms such as dysmorphic features, skin lesions, haematological abnormalities and developmental delay are present; threshold for genetic analysis should be low. Moreover, the presence of autoantibodies should not withhold genetic testing, as our case series contradicts the previous observation of predominant auto-antibody absence in PHID.
Language	English
Publishing date	2024-01-01
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2537278-6
ISSN	1663-2826 ; 1663-2818
ISSN (online)	1663-2826
ISSN	1663-2818
DOI	10.1159/000536019
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Zs.A 414: Show issues

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Article ; Online: High-Throughput Analysis of Neutrophil Extracellular Trap Levels in Subtypes of People with Type 1 Diabetes

Bissenova, Samal / Buitinga, Mijke / Boesch, Markus / Korf, Hannelie / Casteels, Kristina / Teunkens, An / Mathieu, Chantal / Gysemans, Conny

Biology (Basel). 2023 June 19, v. 12, no. 6

2023

Abstract: Neutrophils might play an important role in the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D), by contributing to immune dysregulation via a highly inflammatory program called neutrophil extracellular trap (NET) formation or ... ...

Abstract	Neutrophils might play an important role in the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D), by contributing to immune dysregulation via a highly inflammatory program called neutrophil extracellular trap (NET) formation or NETosis, involving the extrusion of chromatin entangled with anti-microbial proteins. However, numerous studies reported contradictory data on NET formation in T1D. This might in part be due to the inherent heterogeneity of the disease and the influence of the disease developmental stage on neutrophil behavior. Moreover, there is a lack of a standardized method to measure NETosis in an unbiased and robust manner. In this study, we employed the Incucyte® ZOOM live-cell imaging platform to study NETosis levels in various subtypes of adult and pediatric T1D donors compared to healthy controls (HC) at baseline and in response to phorbol–myristate acetate (PMA) and ionomycin. Firstly, we determined that the technique allows for an operator-independent and automated quantification of NET formation across multiple time points, which showed that PMA and ionomycin induced NETosis with distinct kinetic characteristics, confirmed by high-resolution microscopy. NETosis levels also showed a clear dose-response curve to increasing concentrations of both stimuli. Overall, using Incucyte® ZOOM, no aberrant NET formation was observed over time in the different subtypes of T1D populations, irrespective of age, compared to HC. These data were corroborated by the levels of peripheral NET markers in all study participants. The current study showed that live-cell imaging allows for a robust and unbiased analysis and quantification of NET formation in real-time. Peripheral neutrophil measures should be complemented with dynamic quantification of NETing neutrophils to make robust conclusions on NET formation in health and disease.
Keywords	acetates ; adults ; automation ; chromatin ; dose response ; extrusion ; insulin-dependent diabetes mellitus ; microscopy ; neutrophils ; pathogenesis ; people
Language	English
Dates of publication	2023-0619
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12060882
Database	NAL-Catalogue (AGRICOLA)

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Article: High-Throughput Analysis of Neutrophil Extracellular Trap Levels in Subtypes of People with Type 1 Diabetes.

Bissenova, Samal / Buitinga, Mijke / Boesch, Markus / Korf, Hannelie / Casteels, Kristina / Teunkens, An / Mathieu, Chantal / Gysemans, Conny

Biology

2023 Volume 12, Issue 6

Abstract	Neutrophils might play an important role in the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D), by contributing to immune dysregulation via a highly inflammatory program called neutrophil extracellular trap (NET) formation or NETosis, involving the extrusion of chromatin entangled with anti-microbial proteins. However, numerous studies reported contradictory data on NET formation in T1D. This might in part be due to the inherent heterogeneity of the disease and the influence of the disease developmental stage on neutrophil behavior. Moreover, there is a lack of a standardized method to measure NETosis in an unbiased and robust manner. In this study, we employed the Incucyte
Language	English
Publishing date	2023-06-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12060882
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Article ; Online: Near adult height and BMI changes in growth hormone treated short children with Noonan syndrome: the Belgian experience.

De Schepper, Jean / Thomas, Muriel / Huysentruyt, Koen / Becker, Marianne / Boros, Emese / Casteels, Kristina / Chivu, Olimpia / De Waele, Kathleen / Dotremont, Hilde / Lysy, Philippe A / Massa, Guy / Parent, Anne-Simone / Rochtus, Anne / Gies, Inge

Hormone research in paediatrics

2024

Abstract: Introduction A variable near adult height (NAH) outcome after growth hormone (GH) therapy in Noonan syndrome (NS) patients with short stature has been reported. The main objective of this study was to evaluate NAH and body mass index (BMI) evolution in a ...

Abstract	Introduction A variable near adult height (NAH) outcome after growth hormone (GH) therapy in Noonan syndrome (NS) patients with short stature has been reported. The main objective of this study was to evaluate NAH and body mass index (BMI) evolution in a large Belgian cohort of NS patients treated for short stature. The secondary objectives were to investigate whether sex, genotype, the presence of a thoracic deformity and/or a heart anomaly might affect NAH and to validate the recently developed NAH prediction model by Ranke et al. Methods Clinical and auxological data of GH treated short NS patients born before 2001 were extracted from the national Belgrow registry. NAH was available in 54 (35 male) genotyped NS using a gene panel of 9 genes, showing pathogenic variants in PTPN11 in 32 and in SOS1 in 5 patients, while in 17 patients gene panel analysis was inconclusive (no mutation group). Results After a median (P10; P90) duration of 5.4 (2.2-10.3) years of GH therapy with a median dose of 0.05 mg/kg/day NS patients reached a median NAH of -1.7 (-3.4; -0.8) SDS. Median total height gain was 1.1 (0.1; 2.3) SDS. Sex, genotype and the presence of a thoracic or cardiac malformation did not correlate with NAH or total height gain. Linear regression modelling revealed that height SDS at start (beta=0.90, p<0.001), mid-parental height SDS (beta =0.27; p=0.005), birth weight SDS (beta=0.15; p=0.051), age at start (beta=0.07; p=0032) were independently associated with NAH SDS. Median BMI SDS increased significantly (p<0.001) from -1.0 (-2.5; 0.0) at start to -0.2 (-1.5; 0.9) at NAH. The observed NAH in a subgroup of 44 patients with more than 3 years of GH treatment was not statistically different from the predicted NAH by the Noonan NAH prediction model of Ranke. Conclusion Long-term GH therapy at a dose of 0.05 mg/kg/day in short NS patients is effective in improving adult height and BMI, irrespective of the genotype and presence or absence of cardiac and or thoracic anomalies.
Language	English
Publishing date	2024-03-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2537278-6
ISSN	1663-2826 ; 1663-2818
ISSN (online)	1663-2826
ISSN	1663-2818
DOI	10.1159/000538034
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Zs.A 414: Show issues

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Article ; Online: Executive function mediates the link between externalizing behavior and HbA1c in children and adolescents with type 1 diabetes: A cross-national investigation.

Goethals, Eveline R / Lemiere, Jurgen / Snoek, Frank J / Casteels, Kristina / Luyckx, Koen / de Wit, Maartje

Pediatric diabetes

2021 Volume 22, Issue 3, Page(s) 503–510

Abstract: Objective: Externalizing behavior (i.e., conduct problems, hyperactivity) and executive function (EF) problems in children and adolescents with type 1 diabetes (T1D) have been associated with worse diabetes-related and psychosocial outcomes but have not ...

Abstract	Objective: Externalizing behavior (i.e., conduct problems, hyperactivity) and executive function (EF) problems in children and adolescents with type 1 diabetes (T1D) have been associated with worse diabetes-related and psychosocial outcomes but have not been examined in relationship to each other. We aimed to examine whether externalizing behavior is associated with HbA1c and whether this relationship is mediated by EF problems, specifically metacognition (i.e., ability to initiate, plan, organize and monitor behavior) and behavioral regulation (i.e., impulse control, regulation of emotion and behavior). Research design and methods: Cohorts of Belgian and Dutch parents of children and adolescents (6-18 years) with T1D filled out questionnaires on externalizing behavior (Strengths and Difficulties Questionnaire; SDQ) and EF (Behavior Rating Inventory of Executive Function; BRIEF) composite scales. Treating physicians collected HbA1c values. Mediation analyses were performed separately for the BRIEF composite Metacognition and Behavior Regulation scales, correcting for age, sex and diabetes duration. Results: The 335 parents of children and adolescents with T1D (mean age 12.3 ± 2.8 SD; mean HbA1c 7.6% ± 1.1 SD [60 mmol/mol ± 12.0 SD]; mean diabetes duration 5.3 ± 3.6 SD; 49.6% female) participated. Analyses showed that the association between externalizing behavior and HbA1c is mediated by metacognition (ab path Point estimate = 0.05 BCa CI 95% 0.02-0.08), and not behavioral regulation. Conclusions: Results uncovered the influence externalizing behavior may have on EF problems in the metacognition domain, which in turn seem to influence HbA1c. Clinicians should be mindful of these EF problems when working with children and adolescents displaying externalizing behavior, and not only target behavioral but also cognitive processes.
MeSH term(s)	Adolescent ; Belgium ; Child ; Cohort Studies ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/psychology ; Executive Function/physiology ; Female ; Glycated Hemoglobin A/metabolism ; Humans ; Male ; Netherlands ; Problem Behavior ; Surveys and Questionnaires
Chemical Substances	Glycated Hemoglobin A
Language	English
Publishing date	2021-02-07
Publishing country	Denmark
Document type	Journal Article ; 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.13172
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Zs.A 5422: 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: Vitamin D insufficiency in infants with increased risk of developing type 1 diabetes: a secondary analysis of the POInT Study.

Jacobs, An / Warnants, Maarten / Vollmuth, Veronika / Winkler, Christiane / Weiss, Andreas / Ziegler, Anette-Gabriele / Lundgren, Markus / Elding Larsson, Helena / Kordonouri, Olga / von dem Berge, Thekla / Zielmann, Marie-Luise / Bonifacio, Ezio / Hommel, Angela / Ołtarzewski, Mariusz / Szypowska, Agnieszka / Besser, Rachel / Todd, John A / Casteels, Kristina

BMJ paediatrics open

2024 Volume 8, Issue 1

Abstract: Background: Vitamin D insufficiency (VDI) may be a factor in the development of type 1 diabetes (T1D). The aim of this study is to investigate the presence and persistence of VDI in a large cohort of infants with increased risk of developing T1D, in ... ...

Abstract	Background: Vitamin D insufficiency (VDI) may be a factor in the development of type 1 diabetes (T1D). The aim of this study is to investigate the presence and persistence of VDI in a large cohort of infants with increased risk of developing T1D, in light of the differences in local supplementation guidelines. Methods: In the POInT Study, a multicentre primary prevention study between February 2018 and March 2021 in Germany, Poland, Belgium, England and Sweden, including infants aged 4-7 months at high genetic risk of developing β-cell autoantibodies, vitamin D levels were analysed at each study visit from inclusion (4-7 months) until 3 years, with an interval of 2 months (first three visits) or 4-6 months (visits 4-8). The protocol actively promotes vitamin D sufficiency to optimise immune tolerance. VDI was defined as a concentration below 30 ng/mL and was treated according to local guidelines of participating centres. Recovery from VDI was defined as a concentration above or equal to 30 ng/mL on the subsequent visit after VDI. Results: 1050 infants were included, of which 5937 vitamin D levels were available for analyses. VDI was observed in 1464 (24.7%) visits and 507 (46.1%) of these were not resolved at the next visit. The risk of having VDI was independently associated with season (higher in winter), weight (higher with increased weight), age (higher with increased age) and country (higher in England). The risk of not recovering from VDI was independently associated with the season of the previously determined VDI, which was higher if VDI was identified in winter. Conclusions: VDI is frequent in infants with increased risk of developing T1D. Treatment guidelines for VDI do not seem effective. Increasing supplementation dosages in this patient population seems warranted, especially during winter, and increasing dosages more aggressively after VDI should be considered.
MeSH term(s)	Infant ; Humans ; Vitamin D/therapeutic use ; Diabetes Mellitus, Type 1/epidemiology ; Diabetes Mellitus, Type 1/complications ; Vitamin D Deficiency/complications ; Vitamin D Deficiency/epidemiology ; Vitamins ; Risk Factors
Chemical Substances	Vitamin D (1406-16-2) ; Vitamins
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-9772
ISSN (online)	2399-9772
DOI	10.1136/bmjpo-2023-002212
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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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