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Molnár R, Bódy BR, Varga B, Tóth R, Kói T, Gergő D, Garami M, Müller KE, Hegyi P, Ocskay K, Párniczky A. Pancreatic islet autoantibodies and their association with glycemic status in cystic fibrosis patients: A comprehensive meta-analysis. J Cyst Fibros 2025:S1569-1993(25)01466-3. [PMID: 40393876 DOI: 10.1016/j.jcf.2025.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 03/18/2025] [Accepted: 04/28/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND The role of autoimmune beta-cell damage in cystic fibrosis-related glucose abnormalities remains unclear. This study evaluates the prevalence of pancreatic islet autoantibodies (AABs) by glycemic status and age, and assesses the risk of developing cystic fibrosis-related diabetes (CFRD) in people with cystic fibrosis (pwCF). METHODS A random-effects meta-analysis examined AABs against glutamic acid decarboxylase (GADA), insulin (IAA), islet cell (ICA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) in pwCF (CRD42023482663). Prevalence, odds ratios (OR), and 95 % confidence intervals (CI) were calculated with subgroup analyses by glycemic status and age. RESULTS Analysis of 20 studies (2229 pwCF) found an overall islet AAB positivity rate of 4 % (CI: 2-9 %) and multiple positivity at 1 % (CI: 0-11 %). IAA had the highest prevalence at 6 % (CI: 3-14 %), and ICA the lowest at 1 % (CI: 0-9 %). Islet AAB prevalence trended higher in CFRD than non-CFRD patients and in children than adults. CFRD was significantly associated with islet AAB positivity, notably for GADA (OR 4.63, CI: 3.42-6.28), ICA (OR 3.57, CI: 1.05-12.18), and IA-2A (OR 2.36, CI: 1.29-4.34). Any and multiple AAB positivity were similarly correlated to CFRD (OR 2.82, CI: 1.22-6.51 and OR 2.71, CI: 1.49-4.93). CONCLUSIONS Pancreatic islet AABs are present in 1-6 % of pwCF and increase the risk of CFRD by 2.36 to 4.63 times. While there's a suggested link, limited study quality and inconsistent testing warrant cautious interpretation. Further robust studies are needed to confirm these findings and improve screening strategies.
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Affiliation(s)
- Regina Molnár
- Heim Pál National Pediatric Institute, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Blanka Rebeka Bódy
- Heim Pál National Pediatric Institute, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Boróka Varga
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Réka Tóth
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Tamás Kói
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Dorottya Gergő
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Department of Pharmacognosy, Semmelweis University, Budapest, Hungary
| | - Miklós Garami
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Pediatric Center, Semmelweis University, Budapest, Hungary
| | - Katalin Eszter Müller
- Heim Pál National Pediatric Institute, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Department of Family Care Methodology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Institute for Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Klementina Ocskay
- Heim Pál National Pediatric Institute, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Andrea Párniczky
- Heim Pál National Pediatric Institute, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
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Luo J, Guo X, Zheng Y, Yang Z, Pei SY, Rao RQ, Ai Z, Zou F. Integration of multi-omics data and machine learning to identify antioxidant biomarkers in type 1 diabetes. Free Radic Biol Med 2025; 236:41-56. [PMID: 40339726 DOI: 10.1016/j.freeradbiomed.2025.05.385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Revised: 04/08/2025] [Accepted: 05/05/2025] [Indexed: 05/10/2025]
Abstract
The identification of biomarkers for early diagnosis and monitoring the progression of Type 1 Diabetes (T1DM) is essential for improving disease management. This study integrates multi-omics data with machine learning to identify antioxidant stress proteins in serum as potential biomarkers. Serum samples from mice treated with varying doses of streptozotocin (STZ) and human transcriptomic data from the gene expression omnibus (GEO) database were analyzed using weighted gene co-expression network analysis (WGCNA). Proteomic analysis of 25 T1DM and 25 healthy controls using LC-MS/MS revealed 33 differentially expressed proteins enriched in oxidative stress pathways. Machine learning algorithms, including Random Forest and SVM-RFE, identified five key proteins: GPX3, GSTP1, PRDX6, SOD1, and MSRB2. GPX3 demonstrated the highest diagnostic value, with a significant correlation to clinical parameters such as HbA1c and fasting plasma glucose. Functional validation showed GPX3 overexpression protected pancreatic β-cells from H2O2-induced oxidative damage and alleviated symptoms and pathological changes in T1DM mice. These results suggest that GPX3 is a promising biomarker for diagnosing and tracking T1DM progression, offering new insights into oxidative stress management in T1DM.
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Affiliation(s)
- Junming Luo
- Department of Respiratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, PR China
| | - Xin Guo
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, PR China
| | - Yijing Zheng
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, PR China
| | - Zhuoyuan Yang
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, PR China
| | - Si-Ying Pei
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, PR China
| | - Run-Qing Rao
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, PR China
| | - ZhiYing Ai
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, PR China
| | - Fang Zou
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, PR China.
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Alexander L, Cheng-ting T, Åke L, Johan J. Type 1 diabetes, celiac disease, and autoimmune thyroiditis autoantibodies in population-based type 2 diabetes patients. J Clin Transl Endocrinol 2024; 37:100367. [PMID: 39308768 PMCID: PMC11416225 DOI: 10.1016/j.jcte.2024.100367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 08/26/2024] [Accepted: 09/04/2024] [Indexed: 09/25/2024] Open
Abstract
Aims The study aims were to determine autoantibodies associated with type 1 diabetes (T1D), celiac disease (CD) and autoimmune thyroid disease (AITD) in individuals living with type 2 diabetes (T2D) compared to T1D and matched controls. Methods Individuals with T1D and T2D were randomly identified in health-care registers. Blood was collected through home-capillary sampling and autoantibodies associated with either T1D against glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A), CD against tissue transglutaminase (tTGA) or AITD against thyroid peroxidase (TPOA) were determined in an automated, multiplex Antibody Detection by Agglutination-PCR (ADAP) assay. Results GADA were detected in 46 % (88/191) of T1D and increased to 6.2 % (23/372) in T2D compared to 2.6 % (7/259) of controls (p = 0.0367). tTGA was low (1.1-2.6 %) and not different in between the study cohorts, nonetheless, in T1D tTGA was associated to islet autoantibodies. TPOA was more frequent in T1D, 27.1 % (53/191), compared to either T2D, 14.8 % (55/372; p = 0.0002) or controls, 14.3 % (37/259) (p = 0.0004). Overall, TPOA was more frequent in GADA positive (34.8 %; 8/23) than negative (13.5 %; 47/349; p = 0.0053) T2D individuals. Conclusion It's suggested that analyzing GADA and TPOA may refine the autoimmune landscape in individuals clinically classified as T2D.
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Affiliation(s)
- Lind Alexander
- Department of Clinical Sciences Malmö, Lund University CRC, Skåne University Hospital, Malmö, Sweden
| | | | - Lernmark Åke
- Department of Clinical Sciences Malmö, Lund University CRC, Skåne University Hospital, Malmö, Sweden
| | - Jendle Johan
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Sweden
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Mookpaksacharoen O, Choksakunwong S, Lertwattanarak R. Comparison of clinical characteristics and treatment outcomes between initially diagnosed type 1 and type 2 diabetes mellitus patients presenting with diabetic ketoacidosis. BMC Endocr Disord 2024; 24:114. [PMID: 39010018 PMCID: PMC11247844 DOI: 10.1186/s12902-024-01649-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 07/07/2024] [Indexed: 07/17/2024] Open
Abstract
OBJECTIVE Patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) can present with diabetic ketoacidosis (DKA) as the first manifestation. Differentiating types of newly diagnosed diabetes could provide appropriate long-term management. Therefore, we conducted this study to compare clinical characteristics and outcomes between initially diagnosed type 1 and type 2 diabetes mellitus patients presenting with DKA. MATERIALS AND METHODS A retrospective study was conducted on adult patients who presented with DKA as the first diagnosis of diabetes in our tertiary hospital between January 2005 and December 2019. Demographic data, precipitating causes, laboratory investigations, treatment, and outcomes were obtained by chart review. The primary outcome was to compare the clinical characteristics of initially diagnosed patients with T1DM and T2DM who presented with DKA. RESULTS A total of 100 initially diagnosed diabetic patients who presented with DKA were analyzed (85 T2DM patients and 15 T1DM patients). Patients with T1DM were younger than patients with T2DM (mean age 33 ± 16.2 vs. 51 ± 14.5 years, p value < 0.001). Patients with T2DM had a higher body mass index, family history of diabetes, precipitating factors, plasma glucose, and lower renal function than those with T1DM. There was no difference in resolution time or DKA management between T1DM and T2DM patients. The overall mortality rate of DKA was 4%. CONCLUSION In this population, most adult patients who presented with DKA had T2DM. Older age, obesity, a family history of diabetes, and the presence of precipitating factors were strong predictors of T2DM. We can implement the same clinical management for DKA in both T1DM and T2DM patients. However, T2DM patients had longer hospitalization than T1DM patients. After DKA resolution for 12 months, more than half of patients with T2DM could discontinue insulin. Therefore, the accurate classification of the type of diabetes leads to appropriate treatment.
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Affiliation(s)
- Ornwimol Mookpaksacharoen
- Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand
| | - Sawaraj Choksakunwong
- Diabetes, Thyroid and Endocrine Clinic, Siriraj Piyamaharajkarun Hospital, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Raweewan Lertwattanarak
- Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand.
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Sebastiani G, Grieco GE, Bruttini M, Auddino S, Mori A, Toniolli M, Fignani D, Licata G, Aiello E, Nigi L, Formichi C, Fernandez-Tajes J, Pugliese A, Evans-Molina C, Overbergh L, Tree T, Peakman M, Mathieu C, Dotta F. A set of circulating microRNAs belonging to the 14q32 chromosome locus identifies two subgroups of individuals with recent-onset type 1 diabetes. Cell Rep Med 2024; 5:101591. [PMID: 38838677 PMCID: PMC11228666 DOI: 10.1016/j.xcrm.2024.101591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 02/02/2024] [Accepted: 05/13/2024] [Indexed: 06/07/2024]
Abstract
Circulating microRNAs (miRNAs) are linked to the onset and progression of type 1 diabetes mellitus (T1DM), thus representing potential disease biomarkers. In this study, we employed a multiplatform sequencing approach to analyze circulating miRNAs in an extended cohort of prospectively evaluated recent-onset T1DM individuals from the INNODIA consortium. Our findings reveal that a set of miRNAs located within T1DM susceptibility chromosomal locus 14q32 distinguishes two subgroups of individuals. To validate our results, we conducted additional analyses on a second cohort of T1DM individuals, confirming the identification of these subgroups, which we have named cluster A and cluster B. Remarkably, cluster B T1DM individuals, who exhibit increased expression of a set of 14q32 miRNAs, show better glycemic control and display a different blood immunomics profile. Our findings suggest that this set of circulating miRNAs can identify two different T1DM subgroups with distinct blood immunomics at baseline and clinical outcomes during follow-up.
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Affiliation(s)
- Guido Sebastiani
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Giuseppina Emanuela Grieco
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Marco Bruttini
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy; Tuscany Centre for Precision Medicine (CReMeP), Siena, Italy
| | - Stefano Auddino
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Alessia Mori
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy; Tuscany Centre for Precision Medicine (CReMeP), Siena, Italy
| | - Mattia Toniolli
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Daniela Fignani
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Giada Licata
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Elena Aiello
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Laura Nigi
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | - Caterina Formichi
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy
| | | | - Alberto Pugliese
- Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Diabetes Immunology, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, CA, USA
| | - Carmella Evans-Molina
- Center for Diabetes and Metabolic Diseases and the Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Lut Overbergh
- Katholieke Universiteit Leuven/Universitaire Ziekenhuizen, Leuven, Belgium
| | - Timothy Tree
- Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Mark Peakman
- Immunology & Inflammation Research Therapeutic Area, Sanofi, Boston, MA, USA
| | - Chantal Mathieu
- Katholieke Universiteit Leuven/Universitaire Ziekenhuizen, Leuven, Belgium
| | - Francesco Dotta
- Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy; Tuscany Centre for Precision Medicine (CReMeP), Siena, Italy.
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Lind A, Freyhult E, de Jesus Cortez F, Ramelius A, Bennet R, Robinson PV, Seftel D, Gebhart D, Tandel D, Maziarz M, Larsson HE, Lundgren M, Carlsson A, Nilsson AL, Fex M, Törn C, Agardh D, Tsai CT, Lernmark Å. Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays. EBioMedicine 2024; 104:105144. [PMID: 38723553 PMCID: PMC11090024 DOI: 10.1016/j.ebiom.2024.105144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 04/16/2024] [Accepted: 04/18/2024] [Indexed: 05/16/2024] Open
Abstract
BACKGROUND Two or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding assays (RBA) to define threshold levels for diagnostic specificity and sensitivity. METHODS IAA, GADA, IA-2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor's office controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly diagnosed (1-10 years of age) with stage 3 type 1 diabetes. The thresholds for autoantibody positivity were computed in 100 10-fold cross-validations to separate patients from controls either by maximizing the χ2-statistics (chisq) or using the 98th percentile of specificity (Spec98). Mean and 95% CI for threshold, sensitivity and specificity are presented. FINDINGS The ADAP ROC curves of the four autoantibodies showed comparable AUC in the two ADAP laboratories and were higher than RBA. Detection of two or more autoantibodies using chisq showed 0.97 (0.95, 0.99) sensitivity and 0.94 (0.91, 0.97) specificity in ADAP compared to 0.90 (0.88, 0.95) sensitivity and 0.97 (0.94, 0.98) specificity in RBA. Using Spec98, ADAP showed 0.92 (0.89, 0.95) sensitivity and 0.99 (0.98, 1.00) specificity compared to 0.89 (0.77, 0.86) sensitivity and 1.00 (0.99, 1.00) specificity in the RBA. The diagnostic sensitivity and specificity were higher in PBC compared to DOC and BDC. INTERPRETATION ADAP was comparable in two laboratories, both comparable to or better than RBA, to define threshold levels for two or more autoantibodies to stage type 1 diabetes. FUNDING Supported by The Leona M. and Harry B. Helmsley Charitable Trust (grant number 2009-04078), the Swedish Foundation for Strategic Research (Dnr IRC15-0067) and the Swedish Research Council, Strategic Research Area (Dnr 2009-1039). AL was supported by the DiaUnion collaborative study, co-financed by EU Interreg ÖKS, Capital Region of Denmark, Region Skåne and the Novo Nordisk Foundation.
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Affiliation(s)
- Alexander Lind
- Department of Clinical Sciences, Lund University CRC, Malmö, Sweden
| | - Eva Freyhult
- Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | | | - Anita Ramelius
- Department of Clinical Sciences, Lund University CRC, Malmö, Sweden
| | - Rasmus Bennet
- Department of Clinical Sciences, Lund University CRC, Malmö, Sweden
| | | | - David Seftel
- Enable Biosciences Inc., South San Francisco, CA, USA
| | - David Gebhart
- Enable Biosciences Inc., South San Francisco, CA, USA
| | | | - Marlena Maziarz
- Department of Clinical Sciences, Lund University CRC, Malmö, Sweden
| | | | - Markus Lundgren
- Department of Clinical Sciences, Lund University CRC, Malmö, Sweden
| | | | | | - Malin Fex
- Department of Clinical Sciences, Lund University CRC, Malmö, Sweden
| | - Carina Törn
- Department of Clinical Sciences, Lund University CRC, Malmö, Sweden
| | - Daniel Agardh
- Department of Clinical Sciences, Lund University CRC, Malmö, Sweden
| | | | - Åke Lernmark
- Department of Clinical Sciences, Lund University CRC, Malmö, Sweden.
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Pappachan JM, Fernandez CJ, Ashraf AP. Rising tide: The global surge of type 2 diabetes in children and adolescents demands action now. World J Diabetes 2024; 15:797-809. [PMID: 38766426 PMCID: PMC11099374 DOI: 10.4239/wjd.v15.i5.797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 02/09/2024] [Accepted: 03/18/2024] [Indexed: 05/10/2024] Open
Abstract
Childhood-onset obesity has emerged as a major public healthcare challenge across the globe, fueled by an obesogenic environment and influenced by both genetic and epigenetic predispositions. This has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and adolescents. The looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most countries. Unless there is a collective global effort to curb the devastation caused by the situation, the impact is poised to be pro-found. A multifaceted research effort, governmental legislation, and effective social action are crucial in attaining this goal. This article delves into the current epidemiological landscape, explores evidence concerning potential risks and consequences, delves into the pathobiology of childhood obesity, and discusses the latest evidence-based management strategies for diabesity.
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Affiliation(s)
- Joseph M Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, United Kingdom
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
- Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PL, United Kingdom
| | - Cornelius James Fernandez
- Department of Endocrinology & Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston PE21 9QS, United Kingdom
| | - Ambika P Ashraf
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, United States
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8
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Thakkar A, Huang X, Wang J, Hwu K, Chinn IK, Minard C, Hajjar J, Redondo MJ. Elevated Serum IgA at Onset of Type 1 Diabetes in Children. Pediatr Diabetes 2024; 2024:7284088. [PMID: 40302948 PMCID: PMC12016712 DOI: 10.1155/2024/7284088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 01/08/2024] [Accepted: 01/25/2024] [Indexed: 05/02/2025] Open
Abstract
Background Elevated serum IgA levels have been observed in various autoimmune conditions, including type 1 diabetes (T1D). However, whether children with T1D and elevated serum IgA have unique features has not been studied. We aimed to evaluate the prevalence and characteristics associated with elevated serum IgA at the onset of pediatric T1D. Materials and Methods We analyzed demographic, clinical, and laboratory data retrospectively collected from 631 racially diverse children (6 months-18 years of age) with T1D who had serum IgA levels measured within 90 days of T1D diagnosis. Univariable and multivariable logistic regression models were used to identify characteristics that were significantly associated with elevated versus normal IgA. Results Elevated serum IgA was present in 20.3% (128/631) of the children with newly diagnosed T1D. After adjusting for other variables, A1c level (p=0.029), positive insulin autoantibodies (IAA) (p=0.041), negative glutamic acid decarboxylase autoantibodies (GADA) (p=0.005) and Hispanic ethnicity (p < 0.001) were significantly associated with elevated serum IgA. After adjustment for confounders, the odds of elevated serum IgA were significantly increased with positive IAA (OR 1.653, 95% CI 1.019-2.679), higher HbA1c (OR 1.132, 95% CI 1.014-1.268) and Hispanic ethnicity (OR 3.279, 95% CI 2.003-5.359) but decreased with GADA positivity (OR 0.474, 95% CI 0.281-0.805). Conclusions Elevated serum IgA is present in 20.3% of the children at T1D onset and is associated with specific demographic and clinical characteristics, suggesting a unique pathogenesis in a subset of individuals. Further studies are warranted to investigate the IgA response, its role in T1D pathogenesis, and whether these associations persist over time.
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Affiliation(s)
- Amruta Thakkar
- Division of Diabetes and Endocrinology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA
| | | | - Johnny Wang
- Undergraduate School, Rice University, Houston, TX, USA
| | - Kathy Hwu
- Division of Diabetes and Endocrinology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA
| | - Ivan K. Chinn
- Division of Immunology, Allergy and Retrovirology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA
| | | | - Joud Hajjar
- Division of Immunology, Allergy and Retrovirology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Maria J. Redondo
- Division of Diabetes and Endocrinology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA
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Abstract
Despite major advances over the past decade, prevention and treatment of type 1 diabetes mellitus (T1DM) remain suboptimal, with large and unexplained variations in individual responses to interventions. The current classification schema for diabetes mellitus does not capture the complexity of this disease or guide clinical management effectively. One of the approaches to achieve the goal of applying precision medicine in diabetes mellitus is to identify endotypes (that is, well-defined subtypes) of the disease each of which has a distinct aetiopathogenesis that might be amenable to specific interventions. Here, we describe epidemiological, clinical, genetic, immunological, histological and metabolic differences within T1DM that, together, suggest heterogeneity in its aetiology and pathogenesis. We then present the emerging endotypes and their impact on T1DM prediction, prevention and treatment.
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Affiliation(s)
- Maria J Redondo
- Paediatric Diabetes & Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
| | - Noel G Morgan
- Exeter Centre of Excellence for Diabetes Research (EXCEED), Department of Clinical and Biomedical and Science, University of Exeter Medical School, Exeter, UK
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Räisänen LK, Kääriäinen SE, Sund R, Engberg E, Viljakainen HT, Kolho KL. Antibiotic exposures and the development of pediatric autoimmune diseases: a register-based case-control study. Pediatr Res 2023; 93:1096-1104. [PMID: 35854091 PMCID: PMC10033398 DOI: 10.1038/s41390-022-02188-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 05/27/2022] [Accepted: 06/22/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND Antibiotics have been associated with several individual autoimmune diseases (ADs). This study aims to discover whether pre-diagnostic antibiotics are associated with the onset of ADs in general. METHODS From a cohort of 11,407 children, 242 developed ADs (type 1 diabetes, autoimmune thyroiditis, juvenile idiopathic arthritis (JIA), or inflammatory bowel diseases) by a median age of 16 years. Antibiotic purchases from birth until the date of diagnosis (or respective date in the matched controls n = 708) were traced from national registers. RESULTS Total number of antibiotic purchases was not related to the onset of ADs when studied as a group. Of specific diagnoses, JIA was associated with the total number of antibiotics throughout the childhood and with broad-spectrum antibiotics before the age of 3 years. Intriguingly, recent and frequent antibiotic use (within 2 years before diagnosis and ≥3 purchases) was associated with the onset of ADs (OR 1.72, 95% CI 1.08-2.74). Regardless of frequent use in childhood (40% of all antibiotics), penicillin group antibiotics were not related to any ADs. CONCLUSIONS Use of antibiotics was relatively safe regarding the overall development of ADs. However, broad-spectrum antibiotics should be used considerately as they may associate with an increased likelihood of JIA. IMPACT Increasing numbers of antibiotic purchases before the age of 3 years or throughout childhood were not associated with the development of pediatric autoimmune diseases. Broad-spectrum antibiotics were related to the development of autoimmune diseases, especially juvenile idiopathic arthritis in children, while penicillin group antibiotics were not. The use of broad-spectrum antibiotics in children should be cautious as they may carry along a risk for autoimmune disease development.
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Affiliation(s)
- Laura K Räisänen
- Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland
- Folkhälsan Research Center, Helsinki, Finland
- Department of Pediatrics, Tampere University Hospital, Tampere, Finland
| | | | - Reijo Sund
- Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
| | - Elina Engberg
- Folkhälsan Research Center, Helsinki, Finland
- Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Heli T Viljakainen
- Folkhälsan Research Center, Helsinki, Finland
- Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Kaija-Leena Kolho
- Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland.
- Faculty of Medicine, University of Helsinki, Helsinki, Finland.
- Children's Hospital, Helsinki University Hospital, Helsinki, Finland.
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Thewjitcharoen Y, Soontaree N, Waralee C, Siriwan B, Sirinate K, Ekgaluck W, Thep H. Prevalence and characteristics of misdiagnosed adult-onset type 1 diabetes mellitus in Thai people by random plasma C-peptide testing. Heliyon 2023; 9:e14262. [PMID: 36923852 PMCID: PMC10009731 DOI: 10.1016/j.heliyon.2023.e14262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 02/07/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023] Open
Abstract
Background It is critical to determine the exact type of diabetes because misclassification led to inappropriate treatments. The classification of DM can be aided by the measurement of pancreatic autoantibodies and plasma C-peptide levels. Previous studies suggested that random plasma C-peptide testing in those with clinically diagnosed adult T1DM of at least 3 years duration has led to reclassification in some cases. Aim This study aimed to assess the prevalence and characteristics of misdiagnosed adult-onset type 1 diabetes mellitus in Thai people by random plasma C-peptide testing. Methods A cross-sectional study of adult Thai patients diagnosed with clinically diagnosed T1DM and DM duration of at least 3 years at Theptarin Hospital, a diabetes center in Bangkok, Thailand was studied. Clinically misdiagnosis of T1DM was defined by preserved endogenous insulin secretion. Characteristics of the misdiagnosed patients were compared with definite T1DM patients. Results A total of 73 patients (females 52.1%, mean age 42.2 ± 12.5 years, duration of DM 20.3 ± 11.3 years) were studied. The prevalence of available anti-GAD and anti-IA2 were 53.3% and 20.8%, respectively. Preserved endogenous insulin secretion evaluated by random C-peptide or stimulated C-peptide was found in 8 patients (11.0%). The misdiagnosed patients had higher prevalence of hypertension and diabetic complications. Three patients were suspected to have monogenic diabetes and five patients were reclassified as possible T2DM. Conclusions Approximately one-tenth of adult T1DM patients were misdiagnosed. Random plasma C-peptide testing at least 3 years after a diagnosis of T1DM was superior to the measurement of pancreatic autoantibodies. Our present study highlights the need to increase accuracy in the diagnosis of T1DM patients by re-assessing endogenous insulin production with measurement of random plasma C-peptide levels.
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O'Kell AL, Davison LJ. Etiology and Pathophysiology of Diabetes Mellitus in Dogs. Vet Clin North Am Small Anim Pract 2023; 53:493-510. [PMID: 36854636 DOI: 10.1016/j.cvsm.2023.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2023]
Abstract
Canine diabetes results from a wide spectrum of clinical pathophysiological processes that cause a similar set of clinical signs. Various causes of insulin deficiency and beta cell loss, insulin resistance, or both characterize the disease, with genetics and environment playing a role. Understanding the genetic and molecular causes of beta cell loss will provide future opportunities for precision medicine, both from a therapeutic and preventative perspective. This review presents current knowledge of the etiology and pathophysiology of canine diabetes, including the importance of disease classification. Examples of potential targets for future precision medicine-based approaches to therapy are discussed.
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Affiliation(s)
- Allison L O'Kell
- Department of Small Animal Clinical Sciences, University of Florida, 2015 Southwest 16th Avenue, Gainesville, FL 32610, USA.
| | - Lucy J Davison
- Royal Veterinary College, Clinical Sciences and Services, Hawkshead Lane, Hertfordshire AL9 7TA, UK.
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13
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Fan W, Nan X, Peng Y, Li X, Xiang Y, Yan X, Xie Z, Zhou H, Tang X, Cheng J, Niu X, Liu J, Ji Q, Ji L, Huang G, Zhou Z. Distribution of autoantibodies to insulinoma-associated antigen-2 and zinc transporter 8 in type 1 diabetes and latent autoimmune diabetes: A nationwide, multicentre, cross-sectional study. Diabetes Metab Res Rev 2023; 39:e3592. [PMID: 36401613 PMCID: PMC10078268 DOI: 10.1002/dmrr.3592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/18/2022] [Accepted: 10/05/2022] [Indexed: 11/21/2022]
Abstract
AIMS This study investigated insulinoma-associated-2 autoantibody (IA-2A) and zinc transporter 8 autoantibody (ZnT8A) distribution in patients with type 1 diabetes (T1D) and latent autoimmune diabetes (LAD) and the autoantibodies' association with clinical characteristics and HLA-DR-DQ genes. MATERIALS AND METHODS This cross-sectional study recruited 17,536 patients with diabetes from 46 hospitals across China. A total of 189 patients with T1D and 58 patients with LAD with IA-2A positivity, 126 patients with T1D and 86 patients with LAD with ZnT8A positivity, and 231 patients with type 2 diabetes (T2D) were selected to evaluate islet autoantibodies, clinical phenotypes, and HLA-DR-DQ gene frequency. RESULTS IA-2A was bimodally distributed in patients with T1D and LAD. Patients with low IA-2A titre LAD had lower fasting C-peptide (FCP) (p < 0.01), lower postprandial C-peptide (PCP) (p < 0.001), and higher haemoglobin A1c (HbA1c) levels (p < 0.05) than patients with T2D. Patients with high IA-2A titre LAD were younger than patients with low IA-2A titre LAD (p < 0.05). Patients with low IA-2A titre T1D had lower FCP (p < 0.01), lower PCP (p < 0.01), and higher HbA1c levels (p < 0.05) than patients with high IA-2A titre LAD. HLA-DR-DQ genetic analysis demonstrated that the frequency of susceptible HLA haplotypes was higher in IA-2A-positive patients (p < 0.001) than in patients with T2D. Patients with high ZnT8A titre LAD had lower FCP (p = 0.045), lower PCP (p = 0.023), and higher HbA1c levels (p = 0.009) and a higher frequency of total susceptible haplotypes (p < 0.001) than patients with low ZnT8A titre LAD. CONCLUSIONS IA-2A in patients with T1D and LAD was bimodally distributed, and the presence of IA-2A could demonstrate partial LAD clinical characteristics. ZnT8A titre had a certain predictive value for islet functions in patients with LAD.
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Affiliation(s)
- Wenqi Fan
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xixi Nan
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yiman Peng
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xia Li
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yufei Xiang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xiang Yan
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Zhiguo Xie
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Houde Zhou
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xiaohan Tang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Jin Cheng
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xiaohong Niu
- Department of Endocrinology, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Jing Liu
- Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, China
| | - Qiuhe Ji
- Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi an, China
| | - Linong Ji
- Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China
| | - Gan Huang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Zhiguang Zhou
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
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Atapattu N, Amoroso M, Powell M, de Silva DGH, de Silva KSH, Furmaniak J, Rees Smith B, Premawardhana LD. The prevalence of diabetes and thyroid related autoantibodies in Sri Lankan children with type 1 diabetes and their unaffected siblings - The utility of a new screening assay. Front Endocrinol (Lausanne) 2023; 14:1028285. [PMID: 36814577 PMCID: PMC9939822 DOI: 10.3389/fendo.2023.1028285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 01/16/2023] [Indexed: 02/09/2023] Open
Abstract
BACKGROUND There is limited information about diabetes and thyroid related autoantibodies in children with type 1 diabetes (T1D) or their siblings in Sri Lanka. OBJECTIVES To assess in T1D children and their unaffected siblings the prevalence of autoantibodies to (1) glutamic acid decarboxylase (GADA), insulinoma associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) using 3 Screen ICA™ (3-Screen) and individual ELISA assays; (2) insulin (IAA); and (3) thyroid peroxidase (TPOA), thyroglobulin (TgA) and the TSH receptor (TSHRA). METHODS We selected - (a) consecutive T1D children, and (b) their unaffected siblings of both sexes, from the T1D Registry at Lady Ridgeway Hospital, Colombo. RESULTS The median age (IQR) of 235 T1D children and 252 unaffected siblings was 11 (8.4, 13.2) and 9 (5.4, 14.9) years respectively, and the duration of T1D was 23 (7, 54) months. (1) T1D children (a) 79.1% were 3-Screen positive; (b) all 3-Screen positives were individual antibody positive (GADA in 74%; IA-2A 31.1%; ZnT8A 38.7%); (c) and were younger (p=0.01 vs 3-Screen negatives); (d) multiple autoantibodies were present in 45.1%; (e) IA-2A (p=0.002) and ZnT8A (p=0.006) prevalence decreased with T1D duration. (f) TPOA and TgA prevalence was higher in T1D children compared to unaffected siblings (28%, p=0.001 and 31%, p=0.004, respectively). (2) Unaffected siblings (a) 6.3% were 3-Screen positive (p=0.001 vs T1D), and 2.4% were positive for IAA; (b) four subjects had two diabetes related autoantibodies, one of whom developed dysglycaemia during follow-up. CONCLUSIONS The 3-Screen assay, used for the first time in Sri Lankan T1D children and their siblings as a screening tool, shows a high prevalence of T1D related Abs with a high correlation with individual assays, and is also a helpful tool in screening unaffected siblings for future T1D risk. The higher prevalence of thyroid autoantibodies in T1D children is consistent with polyglandular autoimmunity.
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Affiliation(s)
- Navoda Atapattu
- Endocrinology and Diabetes Unit, Lady Ridgeway Hospital, Colombo, Sri Lanka
- *Correspondence: Navoda Atapattu,
| | - Marie Amoroso
- FIRS Laboratories, RSR Ltd., Cardiff, United Kingdom
| | | | - D. G. Harendra de Silva
- Department of Paediatrics, Lady Ridgeway Hospital and Faculty of Medicine, Colombo, Sri Lanka
| | - K. Shamya H. de Silva
- Department of Paediatrics, Lady Ridgeway Hospital and Faculty of Medicine, Colombo, Sri Lanka
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15
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Ward ZJ, Yeh JM, Reddy CL, Gomber A, Ross C, Rittiphairoj T, Manne-Goehler J, Abdalla AT, Abdullah MA, Ahmed A, Ankotche A, Azad K, Bahendeka S, Baldé N, Jain SM, Kalobu JC, Karekezi C, Kol H, Prasannakumar KM, Leik SK, Mbanya JC, Mbaye MN, Niang B, Paturi VR, Raghupathy P, Ramaiya K, Sethi B, Zabeen B, Atun R. Estimating the total incidence of type 1 diabetes in children and adolescents aged 0-19 years from 1990 to 2050: a global simulation-based analysis. Lancet Diabetes Endocrinol 2022; 10:848-858. [PMID: 36372070 DOI: 10.1016/s2213-8587(22)00276-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 09/19/2022] [Accepted: 09/21/2022] [Indexed: 11/12/2022]
Abstract
BACKGROUND Previous studies of type 1 diabetes in childhood and adolescence have found large variations in reported incidence around the world. However, it is unclear whether these reported incidence levels are impacted by differences in country health systems and possible underdiagnosis and if so, to what degree. The aim of this study was to estimate both the total and diagnosed incidence of type 1 diabetes globally and to project childhood type 1 diabetes incidence indicators from 1990 to 2050 for each country. METHODS We developed the type 1 diabetes global microsimulation model to simulate the natural history and diagnosis of type 1 diabetes for children and adolescents (aged 0-19 years) in 200 countries and territories, accounting for variability in underlying incidence and health system performance. The model follows an open population of children and adolescents in monthly intervals and simulates type 1 diabetes incidence and progression, as well as health system factors which influence diagnosis. We calibrated the model to published data on type 1 diabetes incidence, autoantibody profiles, and proportion of cases diagnosed with diabetic ketoacidosis from 1990 to 2020 and assessed the predictive accuracy using a randomly sampled test set of data withheld from calibration. FINDINGS We estimate that in 2021 there were 355 900 (95% UI 334 200-377 300) total new cases of type 1 diabetes globally among children and adolescents, of which 56% (200 400 cases, 95% UI 180 600-219 500) were diagnosed. Estimated underdiagnosis varies substantially by region, with over 95% of new cases diagnosed in Australia and New Zealand, western and northern Europe, and North America, but less than 35% of new cases diagnosed in west Africa, south and southeastern Asia, and Melanesia. The total number of incident childhood cases of type 1 diabetes is projected to increase to 476 700 (95% UI 449 500-504 300) in 2050. INTERPRETATION Our research indicates that the total global incidence of childhood and adolescent type 1 diabetes is larger than previously estimated, with nearly one-in-two children currently undiagnosed. Policymakers should plan for adequate diagnostic and medical capacity to improve timely type 1 diabetes detection and treatment, particularly as incidence is projected to increase worldwide, with highest numbers of new cases in Africa. FUNDING Novo Nordisk.
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Affiliation(s)
- Zachary J Ward
- Center for Health Decision Science, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Health Systems Innovation Lab, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
| | - Jennifer M Yeh
- Health Systems Innovation Lab, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Division of General Pediatrics, Boston Children's Hospital, Harvard Medical School, Harvard University, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA, USA
| | - Che L Reddy
- Health Systems Innovation Lab, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
| | - Apoorva Gomber
- Health Systems Innovation Lab, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
| | - Carlo Ross
- Health Systems Innovation Lab, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Academic Foundation Programme, Manchester University NHS Foundation Trust, Manchester, UK
| | - Thanitsara Rittiphairoj
- Health Systems Innovation Lab, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Division of Health Systems Management, Department of Community Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Jennifer Manne-Goehler
- Health Systems Innovation Lab, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Harvard University, Boston, MA, USA; Medical Practice Evaluation Center, Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, MA, USA
| | - Asmahan T Abdalla
- International University of Africa, College of Medicine, Khartoum, Sudan
| | - Mohamed Ahmed Abdullah
- International University of Africa, College of Medicine, Khartoum, Sudan; Sudanese Childhood Diabetes Association, Khartoum, Sudan
| | - Abdurezak Ahmed
- Department of Internal Medicine, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Amos Ankotche
- Department of Internal Medicine, Endocrinology and Geriatrics, Unit of Training and Research, Medical Science of Abidjan, University of Côte D'Ivoire, Abidjan, Ivory Coast
| | - Kishwar Azad
- BIRDEM and Ibrahim Medical College, Dhaka, Bangladesh
| | - Silver Bahendeka
- Department of Internal Medicine, MKPGMS Uganda Martyrs University, Kampala, Uganda
| | - Naby Baldé
- Department of Endocrinology, University Hospital, Conakry, Guinea
| | - Sunil M Jain
- TOTALL Diabetes Hormone Institute, Indore, Madhya Pradesh, India
| | | | | | - Hero Kol
- Department of Preventive Medicine, Ministry of Health, Phnom Penh, Cambodia
| | | | - Sai Kham Leik
- Department of Social, Economic, and Adminstrative Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand
| | - Jean Claude Mbanya
- Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaoundé, Yaoundé, Cameroon
| | - Maïmouna Ndour Mbaye
- Centre du Diabète Marc Sankalé, Dakar, Senegal; Faculty of Medicine, Cheikh Anta Diop University, Dakar, Senegal
| | - Babacar Niang
- Centre Hospitalier National d'Enfants Albert Royer, Dakar, Sénégal
| | | | - Palany Raghupathy
- Paediatric and Adolescent Endocrinology, Indira Gandhi Institute of Child Health, Bangalore, India
| | | | | | - Bedowra Zabeen
- Department of Paediatrics, Bangladesh Institute of Research & Rehabilitation in Diabetes, Endocrine & Metabolic Disorders, Dhaka, Bangladesh; Changing Diabetes in Children Programme, Diabetic Association of Bangladesh, Dhaka, Bangladesh
| | - Rifat Atun
- Health Systems Innovation Lab, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Department of Global Health and Social Medicine, Harvard Medical School, Harvard University, Boston, MA, USA
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Xie XN, Lei X, Xiao CY, Li YM, Lei XY. Association between type 1 diabetes and neurodevelopmental disorders in children and adolescents: A systematic review and meta-analysis. Front Psychiatry 2022; 13:982696. [PMID: 36483136 PMCID: PMC9722754 DOI: 10.3389/fpsyt.2022.982696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 10/25/2022] [Indexed: 11/23/2022] Open
Abstract
Type 1 diabetes and neurodevelopmental disorders are common chronic conditions in childhood and adolescence, and having one may lead to an increased chance of developing the other. Type 1 diabetes mellitus is mainly manifested by elevated blood glucose, while neurodevelopmental diseases are composed of a variety of diseases, which are relatively complex. The purpose of this meta-analysis was to find out the prevalence of type 1 diabetes-related neurodevelopmental disorders in children and adolescents and to explore the potential association between neurodevelopmental disorders and type 1 diabetes. PubMed, Embase and Web of science databases were searched from the inception to May 22, 2022 to identify relevant studies, Finally, 24 original studies were included in the meta-analysis. Prevalence estimates for neurodevelopmental disorders in the type 1 diabetes adolescent and their 95% confidence intervals were pooled using random effects models. The pooled estimates for autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) in the type 1 diabetes population were 1.2 and 5.3%, respectively, both of which are higher than the 2019 global prevalence of ASD and ADHD in the general population. The results of the subgroup analysis showed that the prevalence of ASD and ADHD in the T1DM population tended to increase with age. In conclusion, there may be a potential link between the occurrence of type 1 diabetes mellitus and the development of neurodevelopmental disorders in children and adolescents, but more relevant studies are needed to understand the link between the underlying pathogenesis of type 1 diabetes and neurodevelopmental disorders. Systematic review registration [https://www.crd.york.ac.uk/PROSPERO/], identifier [CDR42022333443].
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Affiliation(s)
- Xue-Ni Xie
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, China
- School of Public Health, Kunming Medical University, Kunming, China
| | - Xue Lei
- School of Psychology, The University of Queensland, St Lucia, QLD, Australia
| | - Chun-Ye Xiao
- School of Nursing, Jinan University, Guangzhou, China
| | - Ya-Min Li
- Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xian-Yang Lei
- Office of the President, Central South University, Changsha, China
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17
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Limbert C, Lanzinger S, deBeaufort C, Iotova V, Pelicand J, Prieto M, Schiaffini R, Šumnik Z, Pacaud D. Diabetes-related antibody-testing is a valuable screening tool for identifying monogenic diabetes - A survey from the worldwide SWEET registry. Diabetes Res Clin Pract 2022; 192:110110. [PMID: 36183869 DOI: 10.1016/j.diabres.2022.110110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/19/2022] [Accepted: 09/25/2022] [Indexed: 11/26/2022]
Abstract
AIMS To evaluate access to screening tools for monogenic diabetes in paediatric diabetes centres across the world and its impact on diagnosis and clinical outcomes of children and youth with genetic forms of diabetes. METHODS 79 centres from the SWEET diabetes registry including 53,207 children with diabetes participated in a survey on accessibility and use of diabetes related antibodies, c-peptide and genetic testing. RESULTS 73, 63 and 62 participating centres had access to c-peptide, antibody and genetic testing, respectively. Access to antibody testing was associated with higher proportion of patients with rare forms of diabetes identified with monogenic diabetes (54 % versus 17 %, p = 0.01), lower average whole clinic HbA1c (7.7[Q1,Q2: 7.3-8.0]%/61[56-64]mmol/mol versus 9.2[8.6-10.0]%/77[70-86]mmol/mol, p < 0.001) and younger age at onset (8.3 [7.3-8.8] versus 9.7 [8.6-12.7] years p < 0.001). Additional access to c-peptide or genetic testing was not related to differences in age at onset or HbA1c outcome. CONCLUSIONS Clinical suspicion and antibody testing are related to identification of different types of diabetes. Implementing access to comprehensive antibody screening may provide important information for selecting individuals for further genetic evaluation. In addition, worse overall clinical outcomes in centers with limited diagnostic capabilities indicate they may also need support for individualized diabetes management. TRIAL REGISTRATION NCT04427189.
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Affiliation(s)
- Catarina Limbert
- Hospital Dona Estefânia, Unit of Paediatric Endocrinology and Diabetes, Lisbon, Portugal; Nova Medical School, Universidade Nova de Lisboa, Lisbon, Portugal.
| | - Stefanie Lanzinger
- Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, Ulm, Germany; German Centre for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Carine deBeaufort
- Department of Paediatric Diabetes and Endocrinology, Centre Hospitalier Luxembourg, Luxembourg, Luxembourg
| | - Violeta Iotova
- Department of Paediatrics, Medical University of Varna, Varna, Bulgaria
| | - Julie Pelicand
- San Camilo Hospital-Medicine School, Universidad de Valparaíso, San Felipe, Chile
| | - Mariana Prieto
- Servicio de Nutrición, Hospital de Pediatría SAMIC J. P. Garrahan, 1245 Buenos Aieres, Argentina
| | | | - Zdeněk Šumnik
- Department of Paediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
| | - Danièle Pacaud
- Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada; Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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Fiorina P, Pozzilli P. Unveiling a novel type 1 diabetes endotype: Opportunities for intervention. Diabetes Metab Res Rev 2022; 38:e3536. [PMID: 35500886 DOI: 10.1002/dmrr.3536] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Paolo Fiorina
- Division of Endocrinology, Fatebenefratelli-Sacco Hospital, Milan, Italy
- Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Paolo Pozzilli
- Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy
- Centre of Immunobiology, St Bartholomew's and the London School of Medicine, Queen Mary, University of London, London, UK
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Jaryal A, Vikrant S. Anti-Glomerular Basement Membrane Disease in a Patient with Type 2 Diabetic Mellitus: Long term Remission of the two after Immunomodulatory Therapy. Ther Apher Dial 2022; 26:1047-1048. [PMID: 35475565 DOI: 10.1111/1744-9987.13861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/20/2022] [Accepted: 04/22/2022] [Indexed: 11/30/2022]
Affiliation(s)
- Ajay Jaryal
- Department of Nephrology, Indira Gandhi Medical College, Shimla (Himachal Pradesh), INDIA
| | - Sanjay Vikrant
- Department of Nephrology, Indira Gandhi Medical College, Shimla (Himachal Pradesh), INDIA
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Chylińska-Frątczak A, Pietrzak I, Michalak A, Wyka K, Szadkowska A. Autoimmune reaction against pancreatic beta cells in children and adolescents with simple obesity. Front Endocrinol (Lausanne) 2022; 13:1061671. [PMID: 36589801 PMCID: PMC9794760 DOI: 10.3389/fendo.2022.1061671] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 11/21/2022] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION One of the most important complications of obesity is insulin resistance, which leads to carbohydrate metabolism disorders such as type 2 diabetes. However, obesity is also associated with development of an autoimmune response against various organs, including pancreatic beta cells. The prevalence of such autoimmune processes in children and their possible contribution to the increased incidence of type 1 diabetes is currently unclear. Therefore, the present study assessed the prevalence of autoantibodies against pancreatic islet beta cell's antigens in children and adolescents with simple obesity. MATERIAL AND METHODS This prospective observational study included pediatric patients (up to 18 years of age) with simple obesity hospitalized between 2011 and 2016 at the Department of Pediatrics, Diabetology, Endocrinology and Nephrology of the Medical University of Lodz. Children with acute or chronic conditions that might additionally affect insulin resistance or glucose metabolism were excluded. Collected clinical data included sex, age, sexual maturity ratings (Tanner`s scale), body height and weight, waist and hip circumference, amount of body fat and lean body mass. Each participant underwent a 2-hour oral glucose tolerance test with simultaneous measurements of glycaemia and insulinemia at 0`, 60` and 120`. In addition, glycated hemoglobin HbA1c, fasting and stimulated c-peptide, total cholesterol, as well as high- and low-density cholesterol and triglycerides were measured. Insulin resistance was assessed by calculating HOMA-IR index. The following autoantibodies against pancreatic islet beta cells were determined in each child: ICA - antibodies against cytoplasmic antigens of pancreatic islets, GAD - antibodies against glutamic acid decarboxylase, ZnT8 - antibodies against zinc transporter, IA2 - antibodies against tyrosine phosphatase, IAA - antibodies against insulin. RESULTS The study group included 161 children (57.4% boys, mean age 13.1 ± 2.9 years) with simple obesity (mean BMI z-score +2.2 ± 1.6). Among them, 28 (17.4%) were diagnosed with impaired glucose metabolism during OGTT [23 (82.2%) - isolated impaired glucose tolerance (IGT), 3 (10.7%) - isolated impaired fasting glucose (IFG), 2 (7.1%) - IFG and IGT]. Of the children tested, 28 (17.4%) were tested positive for at least one islet-specific autoantibody [with similar percentages in boys (15, 17.4%) and girls (13, 17.3%), p=0.9855], with ICA being the most common (positive in 18, 11.2%), followed by IAA (7, 4.3%), ZnT8 (5, 3.1%), GADA (3, 1.9%) and IA2 (1, 0.6%). There was no association between the presence of the tested antibodies and age, sex, stage of puberty, parameters assessing the degree of obesity, HbA1c, lipid levels and basal metabolic rate. However, autoantibody-positive subjects were more likely to present IFG or IGT in OGTT compared to those who tested completely negative (9, 32.1% vs 19, 14.3%, p=0.0280). Their HOMA-IR was also significantly higher (HOMA-IR: 4.3 ± 1.9 vs 3.4 ± 1.9, p=0.0203) and this difference remained statistically significant after adjusting for sex and age (p=0.0340). CONCLUSIONS Children and adolescents with simple obesity presented a higher prevalence of markers of autoimmune response against pancreatic beta cells than the general population. Most often, they had only one type of antibody - ICA. The presence of autoimmune response indicators against pancreatic islet antigens is more common in obese patients with impaired carbohydrate metabolism and is associated with lower insulin sensitivity.
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Affiliation(s)
- Aneta Chylińska-Frątczak
- Department of Pediatrics, Endocrinology, Diabetology and Nephrology, Maria Konopnicka University Pediatrics Center, Lodz, Poland
| | - Iwona Pietrzak
- Department of Pediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, Lodz, Poland
- *Correspondence: Iwona Pietrzak,
| | - Arkadiusz Michalak
- Department of Pediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, Lodz, Poland
- Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland
| | - Krystyna Wyka
- Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland
| | - Agnieszka Szadkowska
- Department of Pediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, Lodz, Poland
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