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Al-Beltagi M, Bediwy AS, Saeed NK, Bediwy HA, Elbeltagi R. Diabetes-inducing effects of bronchial asthma. World J Diabetes 2025; 16:97954. [PMID: 39817208 PMCID: PMC11718464 DOI: 10.4239/wjd.v16.i1.97954] [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: 06/13/2024] [Revised: 10/12/2024] [Accepted: 11/07/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND The relationship between diabetes mellitus (DM) and asthma is complex and can impact disease trajectories. AIM To explore the bidirectional influences between the two conditions on clinical outcomes and disease control. METHODS We systematically reviewed the literature on the relationship between DM and asthma, focusing on their impacts, mechanisms, and therapeutic implications. Various studies were assessed, which investigated the effect of glycemic control on asthma outcomes, lung function, and exacerbations. The study highlighted the role of specific diabetes medications in managing asthma. RESULTS The results showed that poor glycemic control in diabetes can exacerbate asthma, increase hospitalizations, and reduce lung function. Conversely, severe asthma, especially in obese individuals, can complicate diabetes management and make glycemic control more difficult. The diabetes-associated mechanisms, such as inflammation, microangiopathy, and oxidative stress, can exacerbate asthma and decrease lung function. Some diabetes medications exhibit anti-inflammatory effects that show promise in mitigating asthma exacerbations. CONCLUSION The complex interrelationship between diabetes and asthma suggests bidirectional influences that affect disease course and outcomes. Inflammation and microvascular complications associated with diabetes may worsen asthma outcomes, while asthma severity, especially in obese individuals, complicates diabetes control. However, the current research has limitations, and more diverse longitudinal studies are required to establish causal relationships and identify effective treatment strategies for individuals with both conditions.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatric, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Manama, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Manama, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 26671, Manama, Bahrain
- Medical Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Busaiteen 15503, Muharraq, Bahrain
| | | | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland-Bahrain, Busiateen 15503, Muharraq, Bahrain
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Alduraywish SA, Binnshwan FM, Alhawas RK, Binjadou AF, Alzamil WK, Alghamdi MM, Alhumaid FA, Aldakheel FM, Tharkar S. Prevalence of self-reported asthma in type 1 diabetes children and its associated predictors. Allergol Immunopathol (Madr) 2025; 53:99-105. [PMID: 39786881 DOI: 10.15586/aei.v53i1.1223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 11/28/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND Asthma is considered one of the most common and serious noncommunicable diseases, with high morbidity and mortality rates in both children and adults. OBJECTIVES To estimate the frequency and to determine the associated factors of self-reported asthma among children diagnosed with type 1 diabetes. METHODS A cross-sectional study design was employed, and 175 subjects having type 1 diabetes for more than 1 year were included from the pediatrics endocrine clinic. Validated questionnaires from the International Study of Asthma and Allergies in Childhood (ISAAC) were used for data collection. Statistical analysis was performed using SPSS version 23.0. RESULTS The study included 175 participants (48% boys, 52% girls) with a mean age of 10.9 ± 3.76 years. The majority were of high socioeconomic status, that is, with a monthly family income >15,000 Saudi Riyal (SR) . Notably, 78 participants (44.6%) were diagnosed with type 1 diabetes (2-5 years' duration, and the average age at diagnosis was 7.4 ± 3.27 years). Hospital admissions due to diabetes in the past year were reported in 101 (57.7%) patients. Moreover, 143 (81.7%) participants reported hyperglycemic symptoms, while 125 (71.4%) experienced hypoglycemic symptoms. About 36 (20.6%) participants had self-reported asthma, with wheezing reported in 46 (26.3%) participants. Other sociodemographic and diabetes factors showed no significant associations. The prevalence of self-reported asthma was noted in 36 children with type 1 diabetes (20.6%). The presence of a family history of asthma was the only significant variable associated with self-reported asthma in children with type 1 diabetes (p<0.001). The odds of developing asthma increased by almost 11 times among children with type 1 diabetes who had a positive family history of asthma (p=0.002). Middle-income status also showed increased odds of risk for developing asthma by 4.4 times, but it did not reach the level of statistical significance (p=0.21). CONCLUSION A higher prevalence of self-reported asthma was found among children with type 1 diabetes. Those with a family history of asthma may be considered for screening and educational programs.
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Affiliation(s)
- Shatha A Alduraywish
- Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia;
| | | | | | | | | | | | | | - Fahad M Aldakheel
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Shabana Tharkar
- Prince Sattam bin Abdulaziz Research Chair for Epidemiology and Public Health, Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Weare-Regales N, Carr T, Holguin F, Tibbitt CA, Lockey RF. Obesity and hormonal influences on asthma: Mechanisms, management challenges, and emerging therapeutic strategies. J Allergy Clin Immunol 2024; 154:1355-1368. [PMID: 39362350 DOI: 10.1016/j.jaci.2024.09.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/13/2024] [Accepted: 09/13/2024] [Indexed: 10/05/2024]
Abstract
Obesity and hormone dysregulation, common comorbidities of asthma, not only influence asthma risk and onset but can also complicate its management. The pathobiologic characteristics of obesity, such as insulin resistance and metabolism alterations, can impact lung function and airway inflammation while highlighting potential opportunities for therapeutic intervention. Likewise, obesity alters immune cell phenotypes and corticosteroid pharmacokinetics. Hormones such as sex hormones, incretins, and thyroid hormones can also affect asthma. This review highlights the mechanisms underlying obesity-related asthma and hormonal pathologies while exploring potential therapeutic strategies and the need for more research and innovative approaches in managing these comorbid conditions.
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Affiliation(s)
- Natalia Weare-Regales
- Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, University of South Florida, Morsani College of Medicine, and the Division of Endocrinology, Department of Internal Medicine, James A. Haley Veterans Administration, Tampa.
| | - Tara Carr
- Asthma and Airway Disease Research Center, University of Arizona, and the Section of Allergy and Immunology, Department of Medicine, University of Arizona College of Medicine, Tucson
| | - Fernando Holguin
- Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Medical School, Aurora
| | - Christopher Andrew Tibbitt
- Department of Medicine Huddinge, Centre for Infectious Medicine, Karolinska Institutet, and the Clinical Lung and Allergy Research Medical Unit for Lung and Allergy Diseases, Karolinska University Hospital, Stockholm
| | - Richard F Lockey
- Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Morsani College of Medicine, Tampa
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Carry PM, Vanderlinden LA, Johnson RK, Buckner T, Steck AK, Kechris K, Yang IV, Fingerlin TE, Fiehn O, Rewers M, Norris JM. Longitudinal changes in DNA methylation during the onset of islet autoimmunity differentiate between reversion versus progression of islet autoimmunity. Front Immunol 2024; 15:1345494. [PMID: 38915393 PMCID: PMC11194352 DOI: 10.3389/fimmu.2024.1345494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 05/21/2024] [Indexed: 06/26/2024] Open
Abstract
Background Type 1 diabetes (T1D) is preceded by a heterogenous pre-clinical phase, islet autoimmunity (IA). We aimed to identify pre vs. post-IA seroconversion (SV) changes in DNAm that differed across three IA progression phenotypes, those who lose autoantibodies (reverters), progress to clinical T1D (progressors), or maintain autoantibody levels (maintainers). Methods This epigenome-wide association study (EWAS) included longitudinal DNAm measurements in blood (Illumina 450K and EPIC) from participants in Diabetes Autoimmunity Study in the Young (DAISY) who developed IA, one or more islet autoantibodies on at least two consecutive visits. We compared reverters - individuals who sero-reverted, negative for all autoantibodies on at least two consecutive visits and did not develop T1D (n=41); maintainers - continued to test positive for autoantibodies but did not develop T1D (n=60); progressors - developed clinical T1D (n=42). DNAm data were measured before (pre-SV visit) and after IA (post-SV visit). Linear mixed models were used to test for differences in pre- vs post-SV changes in DNAm across the three groups. Linear mixed models were also used to test for group differences in average DNAm. Cell proportions, age, and sex were adjusted for in all models. Median follow-up across all participants was 15.5 yrs. (interquartile range (IQR): 10.8-18.7). Results The median age at the pre-SV visit was 2.2 yrs. (IQR: 0.8-5.3) in progressors, compared to 6.0 yrs. (IQR: 1.3-8.4) in reverters, and 5.7 yrs. (IQR: 1.4-9.7) in maintainers. Median time between the visits was similar in reverters 1.4 yrs. (IQR: 1-1.9), maintainers 1.3 yrs. (IQR: 1.0-2.0), and progressors 1.8 yrs. (IQR: 1.0-2.0). Changes in DNAm, pre- vs post-SV, differed across the groups at one site (cg16066195) and 11 regions. Average DNAm (mean of pre- and post-SV) differed across 22 regions. Conclusion Differentially changing DNAm regions were located in genomic areas related to beta cell function, immune cell differentiation, and immune cell function.
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Affiliation(s)
- Patrick M. Carry
- Colorado Program for Musculoskeletal Research, Department of Orthopedics, University of Colorado, Aurora, CO, United States
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO, United States
- Department of Biomedical Informatics, School of Medicine, University of Colorado, Aurora, CO, United States
| | | | - Randi K. Johnson
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO, United States
- Department of Biomedical Informatics, School of Medicine, University of Colorado, Aurora, CO, United States
| | - Teresa Buckner
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO, United States
- Department of Kinesiology, Nutrition, and Dietetics, University of Northern Colorado, Greeley, CO, United States
| | - Andrea K. Steck
- Barbara Davis Center, Department of Pediatrics, University of Colorado, Aurora, CO, United States
| | - Katerina Kechris
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO, United States
- Department of Biomedical Informatics, School of Medicine, University of Colorado, Aurora, CO, United States
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, United States
| | - Ivana V. Yang
- Department of Biomedical Informatics, School of Medicine, University of Colorado, Aurora, CO, United States
- Department of Medicine, University of Colorado, Aurora, CO, United States
| | - Tasha E. Fingerlin
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO, United States
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, United States
- Department of Immunology and Genomic Medicine, National Jewish Health, Aurora, CO, United States
| | - Oliver Fiehn
- University of California Davis West Coast Metabolomics Center, Davis, CA, United States
| | - Marian Rewers
- Barbara Davis Center, Department of Pediatrics, University of Colorado, Aurora, CO, United States
| | - Jill M. Norris
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO, United States
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Lin CY, Cheng CW, Ko JL, Lue KH, Liu YF. Multiplexed transcriptional profiling of Dermatophagoides house dust mites allergens in human epithelium cells. ENVIRONMENTAL TOXICOLOGY 2024; 39:2229-2239. [PMID: 38124673 DOI: 10.1002/tox.24109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 12/03/2023] [Accepted: 12/10/2023] [Indexed: 12/23/2023]
Abstract
Allergic asthma, a chronic disease characterized by airway inflammation, poses a significant public health concern. It is well-established that house dust mites (HDMs) are common inducers of allergic responses in individuals, particularly children. In central Taiwan, our research team observed that over 80% of allergic children exhibited sensitization to various HDMs species. This investigation aims to bridge the gap between these observations and a better understanding of the early fundamental mechanisms for preventing allergic diseases. Specifically, our study delves into the impact of crude extracts of HDMs on human epithelial BEAS-2B cells. Our findings, based on RNA sequencing (RNA-seq) analysis, shed light on how three major Dermatophagoides HDMs allergens activate a common Toll-like receptor signaling pathway in human epithelial cells within a 4-h treatment. During this process, the nuclear transcription factor NF-κB translocated into the cell nucleus within 30 min of allergen stimulation, triggering the expression of pro-inflammatory genes such as IL-6 and IL-8 over 4 h. Additionally, when the cells were treated with specific Dermatophagoides microceras (Der m) allergens, it resulted in the upregulation of genes that regulate type 1 diabetes mellitus (T1DM) signaling pathways. This led to the mediation of IL-12A inflammation. Furthermore, there was an increase in gene sets associated with cilia function and the microtubule cytoskeleton in human epithelial cells after treatment with a combination of Der m allergens and Dexamethasone. Additionally, OMICs analysis was conducted to examine the effects of HDMs allergenic stimulation on human epidermal cells. We aimed to improve our understanding of the molecular mechanisms within cells and identify potential targets and natural products in the treatment of asthma caused by HDMs allergens.
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Affiliation(s)
- Chia-Yang Lin
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Family Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chun-Wen Cheng
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Jiunn-Liang Ko
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Ko-Huang Lue
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Division of Allergy, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yu-Fan Liu
- Division of Allergy, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan
- Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan
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Kamei JM, Maués RD, de Oliveira Silva G, Machado AH, Hoshino EM, Bacchiega FM, Sena LMF, Negrato CA. Prevalence of asthma in people with type 1 diabetes mellitus: a scoping review. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2024; 20:12. [PMID: 38331806 PMCID: PMC10851526 DOI: 10.1186/s13223-024-00869-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 01/01/2024] [Indexed: 02/10/2024]
Abstract
BACKGROUND According to the Th1/Th2 paradigm, the expansion of Th1-type clones in individuals with type 1 diabetes results in reduced Th2-type clones, preventing the development of atopic diseases and vice versa. However, there is no consensus regarding the direct or inverse relationship between autoimmune and atopic diseases. OBJECTIVE The aim of this scoping review was to examine the knowledge gap about the possibility of coexistence of asthma and type 1 diabetes and determine the prevalence of this association. METHODS A scoping review was conducted, following the proposal of the Joanna Briggs Institute. The Population, Concept, and Context strategy was used to formulate the guiding question. The proposed question was: "What is the prevalence of asthma in people with T1DM?" After excluding duplicate articles, analyzing titles and abstracts, and excluding articles that did not answer the guiding question, 17 articles remained and were included in this review. RESULTS Most of the articles selected conformed to the Th1/Th2 hypothesis, as the prevalence of asthma was lower in individuals with T1DM. However, similar or higher prevalence of asthma was found between cases and controls in few articles. CONCLUSION The prevalence of asthma in people with T1DM ranged from 1.7% to 23.1%. Maybe the mechanisms that characterizes the Th1/Th2 paradigm aren't as simple as just the interaction of certain cytokines, since Th1-mediated autoimmune diseases and Th2- mediated atopy can coexist.
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Affiliation(s)
- Júlia Marchatto Kamei
- University of São Paulo - Bauru Campus (USP-Bauru), Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, 17012-901, Brazil.
| | - Raissa Dias Maués
- University of São Paulo - Bauru Campus (USP-Bauru), Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, 17012-901, Brazil
| | - Gabriel de Oliveira Silva
- University of São Paulo - Bauru Campus (USP-Bauru), Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, 17012-901, Brazil
| | - Alessandra Helena Machado
- University of São Paulo - Bauru Campus (USP-Bauru), Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, 17012-901, Brazil
| | - Erika Megumi Hoshino
- University of São Paulo - Bauru Campus (USP-Bauru), Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, 17012-901, Brazil
| | - Fabiana Menezes Bacchiega
- University of São Paulo - Bauru Campus (USP-Bauru), Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, 17012-901, Brazil
| | - Laís Mota Furtado Sena
- University of São Paulo - Bauru Campus (USP-Bauru), Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, 17012-901, Brazil
| | - Carlos Antonio Negrato
- University of São Paulo - Bauru Campus (USP-Bauru), Alameda Dr. Octávio Pinheiro Brisolla, 9-75, Bauru, 17012-901, Brazil
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Berg AK, Svensson J, Thyssen JP, Chawes B, Zachariae C, Egeberg A, Thorsen SU. No associations between type 1 diabetes and atopic dermatitis, allergic rhinitis, or asthma in childhood: a nationwide Danish case-cohort study. Sci Rep 2023; 13:19933. [PMID: 37968327 PMCID: PMC10652009 DOI: 10.1038/s41598-023-47292-5] [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: 02/07/2023] [Accepted: 11/11/2023] [Indexed: 11/17/2023] Open
Abstract
Studies examining the association between type 1 diabetes (T1D) and atopic diseases, i.e., atopic dermatitis, allergic rhinitis and asthma have yielded conflicting results due to different algorithms for classification, sample size issues and risk of referral bias of exposed cohorts with frequent contact to health care professionals. Using Danish national registries and well-established disease algorithms, we examined the bidirectional association between T1D and atopic diseases in childhood and adolescence using Cox Proportional Hazard regression compared to two different unexposed cohorts from a population of 1.5 million Danish children born from 1997 to 2018. We found no associations between T1D and atopic dermatitis, allergic rhinitis, or asthma (defined after age five). However, in multivariable analysis we found an increased risk of persistent wheezing (defined as asthma medication before age five) after T1D with an adjusted hazard ratio (aHR) of 1.70 [1.17-2.45]. We also identified an increased risk of developing T1D after persistent wheezing with aHR of 1.24 [1.13-1.36]. This study highlights similar risks of atopic diseases in children with T1D and of T1D in children with atopic disease after age of five years versus healthy controls. However, more research is needed to understand the possible early immunological effects of the link between persistent wheezing and T1D.
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Affiliation(s)
- Anna Korsgaard Berg
- Department of Pediatrics, Herlev and Gentofte Hospital, Herlev, Denmark.
- Steno Diabetes Center Copenhagen, Copenhagen University Hospital, Borgmester Ib Juuls Vej 83, 2730, Herlev, Denmark.
| | - Jannet Svensson
- Department of Pediatrics, Herlev and Gentofte Hospital, Herlev, Denmark
- Steno Diabetes Center Copenhagen, Copenhagen University Hospital, Borgmester Ib Juuls Vej 83, 2730, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jacob P Thyssen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Dermatology and Venerology, Bispebjerg Hospital, København, Denmark
| | - Bo Chawes
- Department of Pediatrics, Herlev and Gentofte Hospital, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Claus Zachariae
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, Gentofte, Denmark
| | - Alexander Egeberg
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Dermatology and Venerology, Bispebjerg Hospital, København, Denmark
| | - Steffen Ullitz Thorsen
- Department of Pediatrics, Herlev and Gentofte Hospital, Herlev, Denmark
- Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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Fu D, Zhao H, Huang Y, Li J, Feng H, Li A, Liu Y, He L. Metformin regulates the effects of IR and IGF-1R methylation on mast cell activation and airway reactivity in diabetic rats with asthma through miR-152-3p/DNMT1 axis. Cell Biol Toxicol 2023; 39:1851-1872. [PMID: 36547818 DOI: 10.1007/s10565-022-09787-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 12/06/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND/AIM Metformin is a drug for treating type 2 diabetes mellitus (T2DM). Recently, metformin has been shown to reduce the risks of asthma-associated outcomes and asthma deterioration, thereby holding promise as a superior medicine for diabetic patients with asthma. However, the mechanism by which metformin reduces diabetic asthma is yet to be clarified. This study aimed at ascertaining the downstream molecules underlying the effect of metformin on the activation of mast cells (MCs) and airway reactivity in a concomitant diabetic and asthmatic rat model. METHODS A T2DM model was induced utilizing a high-fat diet and streptozotocin. Then, 10% ovalbumin was utilized to stimulate asthma-like pathology in the T2DM rats. RBL-2H3 cells were induced by anti-dinitrophenyl-specific immunoglobulin E for constructing an in vitro model. Luciferase assay and RNA immunoprecipitation (IP) assay were conducted to identify the interaction between microRNA-152-3p (miR-152-3p) and DNA methyltransferase 1 (DNMT1), while chromatin IP to identify the binding of DNMT1 to insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF-1R) promoters. The effects of metformin on both pathological changes in vivo and biological behaviors of cells were evaluated. Using gain- and loss-of-function approaches, we assessed the role of the two interactions in the metformin-induced effect. RESULTS It was suggested that metformin could impede the MC activation and airway resistance in the concomitant diabetic and asthmatic rats. Additionally, metformin downregulated IR and IGF-1R through DNMT1-dependent methylation to repress MC activation and airway resistance. DNMT1 was testified to be a target gene of miR-152-3p. Furthermore, miR-152-3p-induced silencing of DNMT1 was blocked by metformin, hence restraining MC activation and airway resistance. CONCLUSION The findings cumulatively demonstrate that metformin downregulates IR/IGF-1R to block MC activation and airway resistance via impairing the binding affinity between miR-152-3p and DNMT1.
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Affiliation(s)
- Dan Fu
- Department of Endocrinology, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People's Republic of China
| | - Hailu Zhao
- Diabetic Systems Center, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin, Guangxi, 541000, People's Republic of China
| | - Yan Huang
- Department of Anesthesiology, The Fifth Affiliated Hospital of Southern Medical University, No.566, Congcheng Ave, Guangzhou, Guangdong, 510900, People's Republic of China
| | - Jingjuan Li
- Department of Anesthesiology, The Fifth Affiliated Hospital of Southern Medical University, No.566, Congcheng Ave, Guangzhou, Guangdong, 510900, People's Republic of China
| | - Huafeng Feng
- Department of Anesthesiology, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541001, People's Republic of China
| | - Aiguo Li
- Department of Anesthesiology, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541001, People's Republic of China
| | - Yefen Liu
- Department of Anesthesiology, The Fifth Affiliated Hospital of Southern Medical University, No.566, Congcheng Ave, Guangzhou, Guangdong, 510900, People's Republic of China
| | - Liang He
- Department of Anesthesiology, The Fifth Affiliated Hospital of Southern Medical University, No.566, Congcheng Ave, Guangzhou, Guangdong, 510900, People's Republic of China.
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Yen FS, Huang JY, Lin SY, Liao PL, Wei JCC. Maternal autoimmune disease associated with a higher risk of offspring with type 1 diabetes: A nationwide mother-child cohort study in Taiwan. DIABETES & METABOLISM 2023; 49:101443. [PMID: 36972847 DOI: 10.1016/j.diabet.2023.101443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 03/17/2023] [Accepted: 03/22/2023] [Indexed: 03/28/2023]
Abstract
AIM The incidence of type 1 diabetes continues to increase. However, the strategies to prevent or reduce its occurrence are inadequate. Therefore, we attempted to investigate if mothers with autoimmune disease were more likely to have children with type 1 diabetes. METHODS We identified 1,288,347 newborns from the Taiwan Maternal and Child Health Database between January 1, 2009, and December 31, 2016, and followed them up to December 31, 2019. We used a multivariable Cox regression model to compare the childhood-onset type 1 diabetes risk between children whose mother had or did not have an autoimmune disease. RESULTS The multivariable model demonstrated significantly higher risks of type 1 diabetes in the children with maternal autoimmune disease (aHR 1.55, 95% CI 1.16-2.08), type 1 diabetes (aHR 11.33, 95% CI 4.62-27.77), Hashimoto's thyroiditis (aHR 3.73, 95% CI 1.70-8.15), and inflammatory bowel diseases (aHR 2.00, 95% CI 1.07-3.76). CONCLUSION This nationwide mother and child cohort study showed a higher risk of type 1 diabetes in the children whose mothers had autoimmune disease, including Hashimoto's thyroiditis, and inflammatory bowel diseases.
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Affiliation(s)
- Fu-Shun Yen
- Dr. Yen's Clinic, No. 15, Shanying Road, Gueishan District, Taoyuan 33354, Taiwan
| | - Jing-Yang Huang
- Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung 40201, Taiwan
| | - Shih-Yi Lin
- Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, No. 1650 Taiwan Boulevard, Sect. 4, Taichung 40705, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong Street, Taipei 11221, Taiwan
| | - Pei-Lun Liao
- Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung 40201, Taiwan
| | - James Cheng-Chung Wei
- Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung 40201, Taiwan; Department of Medicine, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung 40201, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, Taiwan; Department of Medical Research, Taichung Veterans General Hospital, No. 1650 Taiwan Boulevard, Sect. 4, Taichung 40705, Taiwan.
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10
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Liljendahl MS, Sevelsted A, Chawes BL, Stokholm J, Bønnelykke K, Andersen ZJ, Bisgaard H. Childhood asthma is associated with development of type 1 diabetes and inflammatory bowel diseases: a Danish nationwide registry study. Sci Rep 2022; 12:21728. [PMID: 36526660 PMCID: PMC9758130 DOI: 10.1038/s41598-022-26067-4] [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: 04/20/2022] [Accepted: 12/08/2022] [Indexed: 12/23/2022] Open
Abstract
Asthma and autoimmune disorders might be affected by opposing immune mechanisms, T helper cells type 2 (Th2) and T helper cells type 1 (Th1) immunity, respectively. Knowledge on comorbidity can increase understanding of the underlying etiologies. We aim to examine the association between childhood asthma and subsequent risk of type 1 diabetes (T1D) and inflammatory bowel diseases (IBD) in Danish children. Children of Danish origin born during 1991-1996 were included and childhood asthma, defined as a minimum of two collected prescriptions of inhalation corticosteroids age 5-7 years, was linked to hospitalisations with either T1D or IBD after age 8. Associations between childhood asthma and incidence of T1D and IBD were analysed using sex- and year stratified Cox regression. A total of 366,200 children were included in the study, 4.9% had asthma, which increased the risk of both T1D and IBD, hazard ratios of 1.32 (1.08-1.61) and 1.27 (1.09-1.48). In this large nationwide Danish study, we found that children with asthma have increased risk of developing immune diseases T1D and IBD. This contradicts the Th1 vs Th2 paradigm and points towards shared disease mechanisms and risk factors.
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Affiliation(s)
- Mie Sylow Liljendahl
- grid.5254.60000 0001 0674 042XCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Astrid Sevelsted
- grid.5254.60000 0001 0674 042XCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Bo L. Chawes
- grid.5254.60000 0001 0674 042XCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Jakob Stokholm
- grid.5254.60000 0001 0674 042XCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Klaus Bønnelykke
- grid.5254.60000 0001 0674 042XCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Zorana Jovanovic Andersen
- grid.5254.60000 0001 0674 042XSection of Epidemiology, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Hans Bisgaard
- grid.5254.60000 0001 0674 042XCOPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
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11
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Namjou B, Lape M, Malolepsza E, DeVore SB, Weirauch MT, Dikilitas O, Jarvik GP, Kiryluk K, Kullo IJ, Liu C, Luo Y, Satterfield BA, Smoller JW, Walunas TL, Connolly J, Sleiman P, Mersha TB, Mentch FD, Hakonarson H, Prows CA, Biagini JM, Khurana Hershey GK, Martin LJ, Kottyan L, The eMERGE Network. Multiancestral polygenic risk score for pediatric asthma. J Allergy Clin Immunol 2022; 150:1086-1096. [PMID: 35595084 PMCID: PMC9643615 DOI: 10.1016/j.jaci.2022.03.035] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 03/07/2022] [Accepted: 03/29/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND Asthma is the most common chronic condition in children and the third leading cause of hospitalization in pediatrics. The genome-wide association study catalog reports 140 studies with genome-wide significance. A polygenic risk score (PRS) with predictive value across ancestries has not been evaluated for this important trait. OBJECTIVES This study aimed to train and validate a PRS relying on genetic determinants for asthma to provide predictions for disease occurrence in pediatric cohorts of diverse ancestries. METHODS This study applied a Bayesian regression framework method using the Trans-National Asthma Genetic Consortium genome-wide association study summary statistics to derive a multiancestral PRS score, used one Electronic Medical Records and Genomics (eMERGE) cohort as a training set, used a second independent eMERGE cohort to validate the score, and used the UK Biobank data to replicate the findings. A phenome-wide association study was performed using the PRS to identify shared genetic etiology with other phenotypes. RESULTS The multiancestral asthma PRS was associated with asthma in the 2 pediatric validation datasets. Overall, the multiancestral asthma PRS has an area under the curve (AUC) of 0.70 (95% CI, 0.69-0.72) in the pediatric validation 1 and AUC of 0.66 (0.65-0.66) in the pediatric validation 2 datasets. We found significant discrimination across pediatric subcohorts of European (AUC, 95% CI, 0.60 and 0.66), African (AUC, 95% CI, 0.61 and 0.66), admixed American (AUC, 0.64 and 0.70), Southeast Asian (AUC, 0.65), and East Asian (AUC, 0.73) ancestry. Pediatric participants with the top 5% PRS had 2.80 to 5.82 increased odds of asthma compared to the bottom 5% across the training, validation 1, and validation 2 cohorts when adjusted for ancestry. Phenome-wide association study analysis confirmed the strong association of the identified PRS with asthma (odds ratio, 2.71, PFDR = 3.71 × 10-65) and related phenotypes. CONCLUSIONS A multiancestral PRS for asthma based on Bayesian posterior genomic effect sizes identifies increased odds of pediatric asthma.
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Affiliation(s)
- Bahram Namjou
- Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
- Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229
| | - Michael Lape
- Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
- Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229
- Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
| | - Edyta Malolepsza
- Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142
| | - Stanley B. DeVore
- Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229
- Division of Asthma Research, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
| | - Matthew T. Weirauch
- Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
- Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229
- Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
- Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
| | - Ozan Dikilitas
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota 55905
| | - Gail P. Jarvik
- Departments of Medicine (Division of Medical Genetics) and Genome Sciences, University of Washington Medical Center, Seattle, Washington 98195
| | - Krzysztof Kiryluk
- Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, New York 10032
| | - Iftikhar J. Kullo
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota 55905
| | - Cong Liu
- Department of Biomedical Informatics, Columbia University, New York, New York 10032
| | - Yuan Luo
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611
| | | | - Jordan W. Smoller
- Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114
- Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142
- Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115
| | - Theresa L. Walunas
- Division of General Internal Medicine and Geriatrics, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611
| | - John Connolly
- Center for Applied Genomics, Children’s Hospital of Philadelphia, Department of Pediatrics, Philadelphia, Pennsylvania 19104
| | - Patrick Sleiman
- Center for Applied Genomics, Children’s Hospital of Philadelphia, Department of Pediatrics, Philadelphia, Pennsylvania 19104
- Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104
| | - Tesfaye B. Mersha
- Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229
- Division of Asthma Research, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
| | - Frank D Mentch
- Center for Applied Genomics, Children’s Hospital of Philadelphia, Department of Pediatrics, Philadelphia, Pennsylvania 19104
| | - Hakon Hakonarson
- Center for Applied Genomics, Children’s Hospital of Philadelphia, Department of Pediatrics, Philadelphia, Pennsylvania 19104
- Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104
| | - Cynthia A. Prows
- Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229
- Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
- Department of Patient Services, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
| | - Jocelyn M. Biagini
- Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229
- Division of Asthma Research, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
| | - Gurjit K. Khurana Hershey
- Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229
- Division of Asthma Research, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
- Division of Allergy & Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
| | - Lisa J. Martin
- Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229
- Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
| | - Leah Kottyan
- Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
- Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45229
- Division of Allergy & Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229
| | - The eMERGE Network
- National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892
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12
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Xie J, Chen G, Liang T, Li A, Liu W, Wang Y, Wang X, Kuang X, Han D, Liao W, Song L, Zhang X. Childhood asthma and type 1 diabetes mellitus: A meta-analysis and bidirectional Mendelian randomization study. Pediatr Allergy Immunol 2022; 33:e13858. [PMID: 36156818 DOI: 10.1111/pai.13858] [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: 03/17/2022] [Revised: 08/05/2022] [Accepted: 09/06/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Worldwide incidence and prevalence of both asthma and type 1 diabetes mellitus (T1DM) in children have been increasing in past decades. Association between the two diseases has been found in some but not in other studies. OBJECTIVE We conducted a meta-analysis to verify such an association, and bidirectional Mendelian randomization analysis to examine the potential cause-effect relationships. METHODS Three databases (PubMed, Embase, and Web of Science) were searched from their inception to February 1, 2021. Pooled hazard ratios (HR) or odds ratios (OR), and 95% confidence intervals, were calculated. Associations between single-nucleotide polymorphisms with childhood asthma and T1DM were selected based on genome-wide association studies. The outcome datasets were obtained from FinnGen study. We used the inverse-variance-weighted (IVW), weighted median and MR-Egger methods to estimate causal effects. To assess robustness and horizontal pleiotropy, MR-Egger regression and MR pleiotropy residual sum and outlier test were conducted. RESULTS In meta-analysis, childhood asthma was associated with an increased risk of T1DM (HR = 1.30, 95% CI 1.05-1.61, P = .014), whereas T1DM was not associated with the risk of asthma (HR = 0.98, 95% CI 0.64-1.51, P = .941; OR = 0.84, 95% CI 0.65-1.08, P = .168). MR analysis indicated increased genetic risk of T1DM in children with asthma (OR = 1.308; 95% CI 1.030-1.661; P = .028). Analysis using the IVW method indicated no association between T1DM and genetic risk of asthma (OR = 1.027, 95%CI 0.970-1.089, P = .358). CONCLUSION Both meta-analysis and MR study suggested that childhood asthma was a risk factor for T1DM. No epidemiological or genetic evidence was found for an association of T1DM with asthma incidence. Further studies could be carried out to leverage this newfound insight into better clinical and experimental research in asthma and T1DM.
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Affiliation(s)
- Junyang Xie
- State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Innovation and transformation platform of upper airway disease in Guangdong province, Guangzhou, Guangdong, China.,Department of Allergy and Clinical Immunology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Gui Chen
- State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Innovation and transformation platform of upper airway disease in Guangdong province, Guangzhou, Guangdong, China.,Department of Allergy and Clinical Immunology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Tianhao Liang
- State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Innovation and transformation platform of upper airway disease in Guangdong province, Guangzhou, Guangdong, China.,Department of Allergy and Clinical Immunology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Ang Li
- State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Innovation and transformation platform of upper airway disease in Guangdong province, Guangzhou, Guangdong, China.,Department of Allergy and Clinical Immunology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Weixing Liu
- State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Innovation and transformation platform of upper airway disease in Guangdong province, Guangzhou, Guangdong, China.,Department of Allergy and Clinical Immunology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Yiyan Wang
- State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Innovation and transformation platform of upper airway disease in Guangdong province, Guangzhou, Guangdong, China.,Department of Allergy and Clinical Immunology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xiaofen Wang
- State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Innovation and transformation platform of upper airway disease in Guangdong province, Guangzhou, Guangdong, China.,Department of Allergy and Clinical Immunology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xiaoxuan Kuang
- State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Innovation and transformation platform of upper airway disease in Guangdong province, Guangzhou, Guangdong, China.,Department of Allergy and Clinical Immunology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - DeMin Han
- State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Innovation and transformation platform of upper airway disease in Guangdong province, Guangzhou, Guangdong, China.,Department of Allergy and Clinical Immunology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Wenjing Liao
- State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Innovation and transformation platform of upper airway disease in Guangdong province, Guangzhou, Guangdong, China.,Department of Allergy and Clinical Immunology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Lijuan Song
- State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Innovation and transformation platform of upper airway disease in Guangdong province, Guangzhou, Guangdong, China.,Department of Allergy and Clinical Immunology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xiaowen Zhang
- State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Innovation and transformation platform of upper airway disease in Guangdong province, Guangzhou, Guangdong, China.,Department of Allergy and Clinical Immunology, the First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.,Department of Otolaryngology, Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
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13
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Brew BK, Osvald EC, Gong T, Hedman AM, Holmberg K, Larsson H, Ludvigsson JF, Mubanga M, Smew AI, Almqvist C. Paediatric asthma and non-allergic comorbidities: A review of current risk and proposed mechanisms. Clin Exp Allergy 2022; 52:1035-1047. [PMID: 35861116 PMCID: PMC9541883 DOI: 10.1111/cea.14207] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 06/16/2022] [Accepted: 06/27/2022] [Indexed: 11/30/2022]
Abstract
It is increasingly recognized that children with asthma are at a higher risk of other non-allergic concurrent diseases than the non-asthma population. A plethora of recent research has reported on these comorbidities and progress has been made in understanding the mechanisms for comorbidity. The goal of this review was to assess the most recent evidence (2016-2021) on the extent of common comorbidities (obesity, depression and anxiety, neurodevelopmental disorders, sleep disorders and autoimmune diseases) and the latest mechanistic research, highlighting knowledge gaps requiring further investigation. We found that the majority of recent studies from around the world demonstrate that children with asthma are at an increased risk of having at least one of the studied comorbidities. A range of potential mechanisms were identified including common early life risk factors, common genetic factors, causal relationships, asthma medication and embryologic origins. Studies varied in their selection of population, asthma definition and outcome definitions. Next, steps in future studies should include using objective measures of asthma, such as lung function and immunological data, as well as investigating asthma phenotypes and endotypes. Larger complex genetic analyses are needed, including genome-wide association studies, gene expression-functional as well as pathway analyses or Mendelian randomization techniques; and identification of gene-environment interactions, such as epi-genetic studies or twin analyses, including omics and early life exposure data. Importantly, research should have relevance to clinical and public health translation including clinical practice, asthma management guidelines and intervention studies aimed at reducing comorbidities.
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Affiliation(s)
- Bronwyn K. Brew
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetSolnaSweden
- National Perinatal Epidemiology and Statistics Unit, Centre for Big Data Research in Health and School of Clinical MedicineUniversity of New South WalesKensingtonNew South WalesAustralia
| | - Emma Caffrey Osvald
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetSolnaSweden
- Pediatric Allergy and Pulmonology Unit, Astrid Lindgren Children's HospitalKarolinska University HospitalStockholmSweden
| | - Tong Gong
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetSolnaSweden
| | - Anna M. Hedman
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetSolnaSweden
| | - Kirsten Holmberg
- Child Health and Parenting (CHAP), Department of Public Health and Caring SciencesUppsala UniversityUppsalaSweden
| | - Henrik Larsson
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetSolnaSweden
- School of Medical SciencesÖrebro UniversityÖrebroSweden
| | - Jonas F. Ludvigsson
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetSolnaSweden
- Department of PediatricsOrebro University HospitalOrebroSweden
| | - Mwenya Mubanga
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetSolnaSweden
| | - Awad I. Smew
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetSolnaSweden
| | - Catarina Almqvist
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetSolnaSweden
- Pediatric Allergy and Pulmonology Unit, Astrid Lindgren Children's HospitalKarolinska University HospitalStockholmSweden
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14
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Weare-Regales N, Chiarella SE, Cardet JC, Prakash YS, Lockey RF. Hormonal Effects on Asthma, Rhinitis, and Eczema. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:2066-2073. [PMID: 35436605 PMCID: PMC9392967 DOI: 10.1016/j.jaip.2022.04.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 03/18/2022] [Accepted: 04/02/2022] [Indexed: 05/03/2023]
Abstract
Hormones significantly influence the pathogenesis of asthma, rhinitis, and eczema. This review aims to summarize relevant clinical considerations for practicing allergists and immunologists. The first section reviews the effects of sex hormones: estrogen, progesterone, and testosterone. The second concerns insulin production in the context of type 1 and type 2 diabetes. The third concludes with a discussion of thyroid and adrenal pathology in relationship to asthma, rhinitis, and eczema.
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Affiliation(s)
- Natalia Weare-Regales
- Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, University of South Florida, Morsani College of Medicine, Tampa, Fla; Division of Endocrinology, Department of Internal Medicine, James A. Haley Veterans Administration, Tampa, Fla.
| | - Sergio E Chiarella
- Division of Allergic Diseases, Department of Medicine, Mayo Clinic, Rochester, Minn
| | - Juan Carlos Cardet
- Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Morsani College of Medicine, Tampa, Fla
| | - Y S Prakash
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minn; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minn
| | - Richard F Lockey
- Division of Endocrinology, Department of Internal Medicine, James A. Haley Veterans Administration, Tampa, Fla; Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Morsani College of Medicine, Tampa, Fla
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15
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Zeng R, Wang Z, Zhang J, Liang Z, Xu C, Wang J, Dong L. Type 1 diabetes and asthma: a systematic review and meta-analysis of observational studies. Endocrine 2022; 75:709-717. [PMID: 35029744 DOI: 10.1007/s12020-021-02973-x] [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: 10/03/2021] [Accepted: 12/22/2021] [Indexed: 11/03/2022]
Abstract
PURPOSE Type 1 diabetes (T1D) and asthma are both the top concurrent non-communicable diseases in the world, and the existence of a relationship between the two is an area of debate. METHODS All eligible observational studies in PubMed and EMBASE databases from inception to August 2021 were searched for data extraction and analysis. The pooled odds ratio (OR) with corresponding 95% confidence intervals (95% CI) was evaluated using fixed-effects or random-effects models in RevMan 5.3, and I2 and Cochran Q tests were used to assess the heterogeneity. RESULTS 22 studies with 25,578 T1D and 3,330,901 non-T1D were included in this meta-analysis. After data analysis, there seems to be no apparent connectivity between asthma and T1D as the crude OR (cOR) was 1.07 (95%CI, 0.93-1.23). Nevertheless, after limiting the meta-analysis to 6 studies with adjusted OR (aOR) available, the results suggested a positive association between T1D and asthma (aOR, 1.15; 95%CI, 1.06-1.25). Corresponding with this, a meta-analysis of cohort studies also found a positive association between T1D and asthma with the pooled cOR of 1.27 (95% CI, 1.09-1.49) and aOR of 1.15 (95%CI, 1.05-1.26). Further analysis of 7 studies in which the diagnosis of asthma precedes T1D onset revealed that asthma patients are at increased risk of subsequent T1D with the pooled cOR of 1.23 (95%CI, 1.04-1.44) and aOR of 1.58 (95% CI, 1.11-2.24). CONCLUSION Our meta-analysis suggests a possible association between T1D and asthma, and patients who were previously diagnosed with asthma carried higher odds of developing T1D.
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Affiliation(s)
- Rong Zeng
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China
| | - Zihan Wang
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China
| | - Jintao Zhang
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China
| | - Ziting Liang
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China
| | - Changjuan Xu
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China
| | - Jing Wang
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China
| | - Liang Dong
- Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China.
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16
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Cattaneo C, Mameli C, D'Auria E, Zuccotti G, Pagliarini E. The Influence of Common Noncommunicable Diseases on Chemosensory Perception and Clinical Implications in Children and Adolescents. Adv Nutr 2022; 13:234-247. [PMID: 34535793 PMCID: PMC8803496 DOI: 10.1093/advances/nmab100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/08/2021] [Accepted: 08/10/2021] [Indexed: 01/06/2023] Open
Abstract
An increased incidence of noninfectious chronic diseases, such as obesity, diabetes, and allergies, has been noted in the last century, especially in the last 2 to 3 generations. Evidence suggested that the interrelation among these chronic conditions in pediatric age (e.g., children and adolescents aged 4-16 y) is complex and still unknown, reinforcing the interest of pediatricians in these diseases. Of interest is the need to better understand the link between these pathologies and sensory perception, since the chemical senses of taste and smell, together with chemesthesis, are reported to have a role in food choices and may provide a novel target for intervention in the treatment of these pathologies. This review aims to explore the current evidence on the link between these chronic conditions and chemosensory perception (i.e., taste and smell). In addition, the putative role that chemosensory perception may have on food choices and eating behavior of children and adolescents affected by these diseases are highlighted. Furthermore, the review addresses the unexplored issues that need to be investigated in this area. The literature data search suggested that no clear relation between taste and smell perception and the aforementioned diseases in young population yet exists. However, some possible trends have been highlighted in the adult population, in whom the duration of disease might have affected the relation. There is a need for further, high-quality, hypothesis-led research, with robust measures of taste and smell functions as the primary outcomes, to strengthen or deny this evidence.
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Affiliation(s)
- Camilla Cattaneo
- Sensory and Consumer Science Lab (SCS_Lab), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Chiara Mameli
- Department of Pediatrics, V. Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Enza D'Auria
- Department of Pediatrics, V. Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Gianvincenzo Zuccotti
- Department of Pediatrics, V. Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Ella Pagliarini
- Sensory and Consumer Science Lab (SCS_Lab), Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
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17
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Koivusaari K, Syrjälä E, Niinistö S, Ahonen S, Åkerlund M, Korhonen TE, Toppari J, Ilonen J, Kaila M, Knip M, Alatossava T, Veijola R, Virtanen SM. Consumption of differently processed milk products and the risk of asthma in children. Pediatr Allergy Immunol 2022; 33:e13659. [PMID: 34472138 DOI: 10.1111/pai.13659] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 08/25/2021] [Accepted: 08/27/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND Consumption of unprocessed cow's milk has been associated with a lower risk of childhood asthma and/or atopy. Not much is known about differently processed milk products. We aimed to study the association between the consumption of differently processed milk products and asthma risk in a Finnish birth cohort. METHODS We included 3053 children from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study. Asthma and its subtypes were assessed at the age of 5 years, and food consumption by food records, at the age of 3 and 6 months and 1, 2, 3, 4, and 5 years. We used conventional and processing (heat treatment and homogenization)-based classifications for milk products. The data were analyzed using a joint model for longitudinal and time-to-event data. RESULTS At the age of 5 years, 184 (6.0%) children had asthma, of whom 101 (54.9%) were atopic, 75 (40.8%) were nonatopic, and eight (4.3%) could not be categorized. Consumption of infant formulas [adjusted hazard ratio (95% confidence intervals) 1.15 (1.07, 1.23), p < .001] and strongly heat-treated milk products [1.06 (1.01, 1.10), p = .01] was associated with the risk of all asthma. Consumption of all cow's milk products [1.09 (1.03, 1.15), p = .003], nonfermented milk products [1.08 (1.02, 1.14), p = .008], infant formulas [1.23 (1.13, 1.34), p < .001], and strongly heat-treated milk products [1.08 (1.02, 1.15), p = .006] was associated with nonatopic asthma risk. All these associations remained statistically significant after multiple testing correction. CONCLUSIONS High consumption of infant formula and other strongly heat-treated milk products may be associated with the development of asthma.
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Affiliation(s)
- Katariina Koivusaari
- Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland.,Department of Food and Nutrition, University of Helsinki, Helsinki, Finland
| | - Essi Syrjälä
- Faculty of Social Sciences, Unit of Health Sciences, Tampere University, Tampere, Finland
| | - Sari Niinistö
- Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Suvi Ahonen
- Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland.,Faculty of Social Sciences, Unit of Health Sciences, Tampere University, Tampere, Finland.,Research, Development and Innovation Center, Tampere University Hospital, Tampere, Finland
| | - Mari Åkerlund
- Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland.,Faculty of Social Sciences, Unit of Health Sciences, Tampere University, Tampere, Finland.,Research, Development and Innovation Center, Tampere University Hospital, Tampere, Finland
| | - Tuuli E Korhonen
- Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Jorma Toppari
- Department of Pediatrics, Turku University Hospital, Turku, Finland.,Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Jorma Ilonen
- Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Minna Kaila
- Public Health Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Department of Pediatrics, Tampere University Hospital, Tampere, Finland
| | - Mikael Knip
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.,Folkhälsan Research Center, Helsinki, Finland
| | - Tapani Alatossava
- Department of Food and Nutrition, University of Helsinki, Helsinki, Finland
| | - Riitta Veijola
- Department of Pediatrics, PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
| | - Suvi M Virtanen
- Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland.,Faculty of Social Sciences, Unit of Health Sciences, Tampere University, Tampere, Finland.,Research, Development and Innovation Center, Tampere University Hospital, Tampere, Finland.,Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
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18
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Franks PW, Melén E, Friedman M, Sundström J, Kockum I, Klareskog L, Almqvist C, Bergen SE, Czene K, Hägg S, Hall P, Johnell K, Malarstig A, Catrina A, Hagström H, Benson M, Gustav Smith J, Gomez MF, Orho-Melander M, Jacobsson B, Halfvarson J, Repsilber D, Oresic M, Jern C, Melin B, Ohlsson C, Fall T, Rönnblom L, Wadelius M, Nordmark G, Johansson Å, Rosenquist R, Sullivan PF. Technological readiness and implementation of genomic-driven precision medicine for complex diseases. J Intern Med 2021; 290:602-620. [PMID: 34213793 DOI: 10.1111/joim.13330] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 03/21/2021] [Accepted: 04/12/2021] [Indexed: 12/20/2022]
Abstract
The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.
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Affiliation(s)
- P W Franks
- From the, Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden.,Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
| | - E Melén
- Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | - M Friedman
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - J Sundström
- Department of Cardiology, Akademiska Sjukhuset, Uppsala, Sweden.,George Institute for Global Health, Camperdown, NSW, Australia.,Medical Sciences, Uppsala University, Uppsala, Sweden
| | - I Kockum
- Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.,Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - L Klareskog
- Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.,Department of Rheumatology, Karolinska Institutet, Stockholm, Sweden
| | - C Almqvist
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - S E Bergen
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - K Czene
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - S Hägg
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - P Hall
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Department of Oncology, Södersjukhuset, Stockholm, Sweden
| | - K Johnell
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - A Malarstig
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Pfizer, Worldwide Research and Development, Stockholm, Sweden
| | - A Catrina
- Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - H Hagström
- Department of Medicine, Karolinska Institutet, Stockholm, Sweden.,Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden
| | - M Benson
- Department of Pediatrics, Linkopings Universitet, Linkoping, Sweden.,Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - J Gustav Smith
- Department of Cardiology and Wallenberg Center for Molecular Medicine, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden.,Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - M F Gomez
- From the, Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden
| | - M Orho-Melander
- From the, Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden
| | - B Jacobsson
- Division of Health Data and Digitalisation, Norwegian Institute of Public Health, Genetics and Bioinformatics, Oslo, Norway.,Department of Obstetrics and Gynecology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.,Department of Obstetrics and Gynecology, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden
| | - J Halfvarson
- School of Medical Sciences, Örebro University, Örebro, Sweden
| | - D Repsilber
- Functional Bioinformatics, Örebro University, Örebro, Sweden
| | - M Oresic
- School of Medical Sciences, Örebro University, Örebro, Sweden.,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, FI, Finland
| | - C Jern
- Department of Clinical Genetics and Genomics, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.,Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
| | - B Melin
- Department of Radiation Sciences, Oncology, Umeå Universitet, Umeå, Sweden
| | - C Ohlsson
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, CBAR, University of Gothenburg, Gothenburg, Sweden.,Department of Drug Treatment, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - T Fall
- Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden
| | - L Rönnblom
- Department of Medical Sciences, Rheumatology & Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - M Wadelius
- Department of Medical Sciences, Clinical Pharmacogenomics & Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - G Nordmark
- Department of Medical Sciences, Rheumatology & Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Å Johansson
- Institute for Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden
| | - R Rosenquist
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - P F Sullivan
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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19
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Stress hyperglycemia as first sign of asymptomatic type 1 diabetes: an instructive case. BMC Pediatr 2021; 21:335. [PMID: 34362315 PMCID: PMC8343951 DOI: 10.1186/s12887-021-02811-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 07/12/2021] [Indexed: 11/24/2022] Open
Abstract
Background Stress hyperglycemia (SH) is considered a transient manifestation and routine diagnostic evaluation was thought to be unnecessary due to the lack of definite correlation with diabetes mellitus (DM). Although SH was usually benign and long-term treatment was superfluous, it might be the first sign of insulinopenic status such as type 1 DM (T1DM). Case presentation We reported a boy with acute asthma attack presented incidentally with high blood glucose levels exceeding 300 mg/dL and obvious glycemic variability. A prolonged hyperglycemic duration of more than 48 h was also noticed. To elucidate his unique situation, glucagon test and insulin autoantibody survey were done which showed insulinopenia with positive anti-insulin antibody and glutamic acid decarboxylase antibody despite the absence of overt DM symptoms and signs. Conclusions This case highlights that SH might be a prodromal presentation in T1DM children, especially when accompanied simultaneously with extreme hyperglycemia, apparent glucose variability, as well as prolonged hyperglycemic duration.
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20
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Abstract
PURPOSE OF REVIEW Disorders of glucose metabolism, including insulin resistance, prediabetes, and diabetes, have been identified as risk factors for worsened asthma. This review summarizes emerging evidence for their role as modifiable risk factors in asthma, including the potential benefit of diabetes medications on asthma outcomes. RECENT FINDINGS Experimental studies show that hyperinsulinemia associated with insulin resistance is associated with airway smooth muscle proliferation and promotes contractility. Epidemiologic studies have identified a higher prevalence of glycemic dysfunction among those with severe and uncontrolled asthma, and longitudinal studies have associated prediabetes and diabetes with higher risk of asthma exacerbations. The potential benefits of thiazolidinediones (TZDs), glucagon-like peptide-1 agonists, and metformin being investigated in asthma, but thus far interventional studies of TZDs have reported null results. On the contrary, observational studies have inconsistently controlled for relevant confounders which leaves conclusions vulnerable to misattribution of relationships due to corelated metabolic disorders, including dyslipidemia. SUMMARY Developing evidence suggests that disorders of glucose metabolism may be associated with worsening asthma. However, these conditions arise within a network of obesity-related metabolic diseases that may themselves worsen asthma. Few interventional trials have not identified a benefit, but data have been limited. Additional research is needed to define the potential independent impact of disorders of glucose metabolism in asthma.
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21
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Sgrazzutti L, Sansone F, Attanasi M, Di Pillo S, Chiarelli F. Coaggregation of Asthma and Type 1 Diabetes in Children: A Narrative Review. Int J Mol Sci 2021; 22:ijms22115757. [PMID: 34071190 PMCID: PMC8198343 DOI: 10.3390/ijms22115757] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 05/20/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Asthma and type 1 diabetes mellitus (T1DM) are two of the most frequent chronic diseases in children, representing a model of the atopic and autoimmune diseases respectively. These two groups of disorders are mediated by different immunological pathways, T helper (Th)1 for diabetes and Th2 for asthma. For many years, these two groups were thought to be mutually exclusive according to the Th1/Th2 paradigm. In children, the incidence of both diseases is steadily increasing worldwide. In this narrative review, we report the evidence of the potential link between asthma and T1DM in childhood. We discuss which molecular mechanisms could be involved in the link between asthma and T1DM, such as genetic predisposition, cytokine patterns, and environmental influences. Cytokine profile of children with asthma and T1DM shows an activation of both Th1 and Th2 pathways, suggesting a complex genetic-epigenetic interaction. In conclusion, in children, the potential link between asthma and T1DM needs further investigation to improve the diagnostic and therapeutic approach to these patients. The aim of this review is to invite the pediatricians to consider the potential copresence of these two disorders in clinical practice.
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22
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Lamminsalo A, Lundqvist A, Virta LJ, Gissler M, Kaila M, Metsälä J, Virtanen SM. Cow's milk allergy in infancy and later development of type 1 diabetes-nationwide case-cohort study. Pediatr Diabetes 2021; 22:400-406. [PMID: 33470004 DOI: 10.1111/pedi.13181] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 12/09/2020] [Accepted: 12/15/2020] [Indexed: 12/15/2022] Open
Abstract
BAKGROUND It is suggested that early intake of cow's milk could be a risk factor for type 1 diabetes (T1DM). Further, the different immunological background, gives a suggestion of an inverse relationship for the occurrence of these diseases. The aim of this study was to explore the association between cow's milk allergy (CMA) and the risk of T1DM in a register-based case-cohort study. METHODS Data were obtained from Finnish nationwide health registers. The study included all children born in Finland between January 01, 1986 and December 31, 2008 and diagnosed with T1DM before the age of 16 years (n = 7754). A 10% random sample from each birth year cohort was selected as a reference cohort (n = 137,798). T1DM, CMA, and asthma were defined based on valid special reimbursements for the costs of drugs/special formulas needed in the treatment of the diseases. Child's sex, birth decade, asthma, maternal diabetes and asthma, smoking during pregnancy, and previous deliveries were considered as confounding factors. Time-dependent, weighted Cox regression was applied for statistical analyses. RESULTS Children with CMA had an increased risk of developing T1DM in fully adjusted model (HR = 1.17; 95% CI 1.02-1.34), but the association was no longer observed when including the use of special infant formulas in the definition of CMA in the sensitivity analysis (HR = 1.11; 95% CI 0.92-1.32). CMA was associated with an increased risk of T1DM in children without asthma (HR = 1.27; 95%CI 1.10-1.47), but not in children with asthma (HR = 0.80; 95% CI 0.92-1.27). CONCLUSION Children with CMA may have an increased risk of T1DM.
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Affiliation(s)
- Anni Lamminsalo
- Faculty of Social Sciences, Unit of Health Sciences, Tampere University, Tampere, Finland.,Research, Development, and Innovation Center, Tampere University Hospital, Tampere, Finland
| | - Annamari Lundqvist
- Public Health Solutions Department, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Lauri J Virta
- Research Department, Social Insurance Institution, Turku, Finland
| | - Mika Gissler
- Information Services Department, Finnish Institute for Health and Welfare, Helsinki, Finland.,Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden
| | - Minna Kaila
- Public Health Medicine, University of Helsinki, Helsinki University Hospital, Helsinki, Finland.,Department of Paediatrics, Tampere University Hospital, Tampere, Finland
| | - Johanna Metsälä
- Public Health Solutions Department, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Suvi M Virtanen
- Faculty of Social Sciences, Unit of Health Sciences, Tampere University, Tampere, Finland.,Research, Development, and Innovation Center, Tampere University Hospital, Tampere, Finland.,Public Health Solutions Department, Finnish Institute for Health and Welfare, Helsinki, Finland.,Center for Child Health Research, Tampere University, Tampere University Hospital, Tampere, Finland
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23
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Mameli C, Ghezzi M, Mari A, Cammi G, Macedoni M, Redaelli FC, Calcaterra V, Zuccotti G, D’Auria E. The Diabetic Lung: Insights into Pulmonary Changes in Children and Adolescents with Type 1 Diabetes. Metabolites 2021; 11:69. [PMID: 33530418 PMCID: PMC7912250 DOI: 10.3390/metabo11020069] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/21/2021] [Accepted: 01/22/2021] [Indexed: 12/13/2022] Open
Abstract
Historically, the lung was not listed and recognized as a major target organ of diabetic injury. The first evidence of diabetic lung involvement was published fifty years ago, with a study conducted in a population of young adults affected by type 1 diabetes (T1D). In recent years, there has been mounting evidence showing that the lung is a target organ of diabetic injury since the beginning of the disease-at the pediatric age. The deeply branched vascularization of the lungs and the abundance of connective tissue, indeed, make them vulnerable to the effects of hyperglycemia, in a way similar to other organs affected by microvascular complications. In this review, we focus on pulmonary function impairment in children and adolescents affected by T1D. We also cover controversial aspects regarding available studies and future perspectives in this field.
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Affiliation(s)
- Chiara Mameli
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (M.G.); (A.M.); (G.C.); (M.M.); (F.C.R.); (V.C.); (G.Z.); (E.D.)
- Department of Biomedical and Clinical Science “L. Sacco”, Università di Milano, 20157 Milan, Italy
| | - Michele Ghezzi
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (M.G.); (A.M.); (G.C.); (M.M.); (F.C.R.); (V.C.); (G.Z.); (E.D.)
- Allergology and Pneumology Unit, V. Buzzi Children’s Hospital, 20154 Milan, Italy
| | - Alessandra Mari
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (M.G.); (A.M.); (G.C.); (M.M.); (F.C.R.); (V.C.); (G.Z.); (E.D.)
| | - Giulia Cammi
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (M.G.); (A.M.); (G.C.); (M.M.); (F.C.R.); (V.C.); (G.Z.); (E.D.)
| | - Maddalena Macedoni
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (M.G.); (A.M.); (G.C.); (M.M.); (F.C.R.); (V.C.); (G.Z.); (E.D.)
| | - Francesca Chiara Redaelli
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (M.G.); (A.M.); (G.C.); (M.M.); (F.C.R.); (V.C.); (G.Z.); (E.D.)
| | - Valeria Calcaterra
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (M.G.); (A.M.); (G.C.); (M.M.); (F.C.R.); (V.C.); (G.Z.); (E.D.)
- Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy
| | - Gianvincenzo Zuccotti
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (M.G.); (A.M.); (G.C.); (M.M.); (F.C.R.); (V.C.); (G.Z.); (E.D.)
- Department of Biomedical and Clinical Science “L. Sacco”, Università di Milano, 20157 Milan, Italy
| | - Enza D’Auria
- Department of Pediatrics, V. Buzzi Children’s Hospital, 20154 Milan, Italy; (M.G.); (A.M.); (G.C.); (M.M.); (F.C.R.); (V.C.); (G.Z.); (E.D.)
- Allergology and Pneumology Unit, V. Buzzi Children’s Hospital, 20154 Milan, Italy
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24
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Krischer JP, Cuthbertson D, Couluris M, Knip M, Virtanen SM. Association of diabetes-related autoantibodies with the incidence of asthma, eczema and allergic rhinitis in the TRIGR randomised clinical trial. Diabetologia 2020; 63:1796-1807. [PMID: 32548702 PMCID: PMC7416479 DOI: 10.1007/s00125-020-05188-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 04/15/2020] [Indexed: 11/24/2022]
Abstract
AIMS/HYPOTHESIS This paper presents the relationship between islet autoantibodies, precursors of type 1 diabetes, and the development of persistent asthma, allergic rhinitis and atopic eczema. METHODS A total of 2159 newborns who had a first-degree relative with type 1 diabetes and selected HLA genotypes were followed until the youngest participant reached 10 years of age. Islet cell antibodies (ICA) were detected using indirect immunofluorescence. Autoantibodies to insulin (IAA), GAD (GADA), the tyrosine phosphatase-related insulinoma-associated 2 molecule (IA-2A) and zinc transporter 8 (ZnT8A) were quantified with the use of specific radiobinding assays. As an ancillary study, the incidence of asthma, allergic rhinitis and eczema was assessed in 1106 of these children using the International Study of Asthma and Allergies in Childhood (ISAAC) core questionnaire when the children were 9-11 years old. HRs with 95% CIs were calculated to depict the incidence of these diseases following seroconversion to autoantibody positivity. RESULTS The cumulative incidence of atopic eczema, allergic rhinitis and persistent asthma were 22%, 9% and 7.5%, respectively, by 9-11 years of age. The occurrence of diabetes-related autoantibodies showed a protective association with subsequently reported incidence of asthma and eczema. The incidence of rhinitis was not significantly related to the occurrence of IAA or GADA (statistical power was limited), but demonstrated the same inverse relationship as did the other diseases with ICA or when multiple autoantibodies first appeared together. CONCLUSIONS/INTERPRETATION The findings add evidence to the relationships between these atopic diseases and diabetes-related autoimmunity and also suggest that, for eczema, the interaction depends upon which autoantibody appeared first. TRIAL REGISTRATION ClinicalTrials.gov NCT00179777 Graphical abstract.
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Affiliation(s)
- Jeffrey P Krischer
- Health Informatics Institute, Morsani College of Medicine, University of South Florida, 3650 Spectrum Boulevard, Suite 100, Tampa, FL, 33612, USA.
| | - David Cuthbertson
- Health Informatics Institute, Morsani College of Medicine, University of South Florida, 3650 Spectrum Boulevard, Suite 100, Tampa, FL, 33612, USA
| | - Marisa Couluris
- Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
| | - Mikael Knip
- Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Suvi M Virtanen
- Unit of Public Health Promotion, National Institute for Health and Welfare, Helsinki, Finland
- Faculty of Social Sciences/Health Sciences, Tampere University, Tampere, Finland
- Research, Development and Innovation Center, Tampere University Hospital, Tampere, Finland
- Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
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Metsälä J, Lundqvist A, Virta LJ, Kaila M, Gissler M, Virtanen SM, Nevalainen J. Use of Antiasthmatic Drugs and the Risk of Type 1 Diabetes in Children: A Nationwide Case-Cohort Study. Am J Epidemiol 2020; 189:779-787. [PMID: 31971234 DOI: 10.1093/aje/kwaa002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 01/06/2020] [Indexed: 12/15/2022] Open
Abstract
Asthma has been reported to be associated with an increased risk of type 1 diabetes mellitus in childhood, but the reasons are unclear. We examined whether the use of antiasthmatic drugs was associated with the development of type 1 diabetes in childhood in a nationwide, register-based case-cohort study. We identified all children who were born January 1, 1995, through December 31, 2008, in Finland and diagnosed with type 1 diabetes by 2010 (n = 3,342). A 10% random sample from each birth-year cohort was selected as a reference cohort (n = 80,909). Information on all dispensed antiasthmatic drugs (Anatomical Therapeutic Chemical classification system code R03) during 1995-2009 was obtained, and associations between the use of antiasthmatic drugs and the development of type 1 diabetes were investigated using time-dependent and time-sequential Cox regression models. Dispensed inhaled corticosteroids and inhaled β-agonists were associated with an increased risk of type 1 diabetes after adjusting for other antiasthmatic drugs, asthma, sex, and birth decade (hazard ratio = 1.29, 95% confidence interval: 1.09, 1.52, and hazard ratio = 1.22, 95% confidence interval: 1.07, 1.41, respectively). These findings suggest that children using inhaled corticosteroids or inhaled β-agonists might be at increased risk of type 1 diabetes.
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Affiliation(s)
- Johanna Metsälä
- Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Annamari Lundqvist
- Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Lauri J Virta
- Research Department, Social Insurance Institution, Turku, Finland
| | - Minna Kaila
- Public Health Medicine, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Mika Gissler
- Information Services Department, Finnish Institute for Health and Welfare, Helsinki, Finland
- Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden
| | - Suvi M Virtanen
- Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland
- Science Centre, Tampere University Hospital, Tampere, Finland
- Tampere Center for Child Health Research, Tampere University and Tampere University Hospital, Finland
- Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Jaakko Nevalainen
- Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland
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Metsälä J, Hakola L, Lundqvist A, Virta LJ, Gissler M, Virtanen SM. Perinatal factors and the risk of type 1 diabetes in childhood and adolescence-A register-based case-cohort study in Finland, years 1987 to 2009. Pediatr Diabetes 2020; 21:586-596. [PMID: 32003515 DOI: 10.1111/pedi.12994] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 01/02/2020] [Accepted: 01/27/2020] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVES Our aim was to clarify previously reported associations and to explore new ones between various maternal background and perinatal factors and the risk of type 1 diabetes in childhood. METHODS We identified all children born 1 January 1987 to 31 December 2008 in Finland and diagnosed with type 1 diabetes by age 16 years or end of 2009 from the Special Reimbursement Register (n = 6862). A 10% random sample from each birth year cohort was selected as a reference cohort (n = 127 216). Information on perinatal factors was obtained from the Finnish Medical Birth Register. RESULTS Maternal diabetes (hazard ratios [HR] = 6.43; 95% confidence interval [CI] 5.35, 7.73), maternal asthma (HR = 1.23; 95% CI 1.06, 1.43), child's high birth length for gestational age (HR = 1.35; 95% CI 1.22, 1.51 highest vs lowest quintile) and premature or early term birth (HR = 1.21; 95% CI 1.05, 1.39 gestational weeks 33-36 and HR = 1.17; 95% CI 1.09, 1.26 gestational weeks 37-38 vs gestational weeks 39-40) was associated with an increased risk of type 1 diabetes when adjusted for several potential confounders. Maternal smoking during pregnancy (HR = 0.72; 95% CI 0.66, 0.77), high number of previous live births (HR = 0.65; 95% CI 0.55, 0.76 ≥ 4 vs 0 live births), and the child being born small for gestational age (HR = 0.80; 95% CI 0.67, 0.96) was associated with a decreased risk of type 1 diabetes. CONCLUSIONS Findings on maternal asthma and high birth length for gestational age increasing the risk of type 1 diabetes are novel and need to be confirmed. Our findings indicate that perinatal factors may play a role in the development of type 1 diabetes.
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Affiliation(s)
- Johanna Metsälä
- Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Leena Hakola
- Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Annamari Lundqvist
- Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Lauri J Virta
- Research Department, Social Insurance Institution, Turku, Finland
| | - Mika Gissler
- Information Services Department, Finnish Institute for Health and Welfare, Helsinki, Finland.,Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden
| | - Suvi M Virtanen
- Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland.,Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland.,Tampere Center for Child Health Research, Tampere University and Tampere University Hospital, Finland.,Science Centre, Tampere University Hospital, Tampere, Finland
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27
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Virtanen SM, Knip M. Type 1 diabetes-origins and epidemiology. Lancet Diabetes Endocrinol 2020; 8:368-369. [PMID: 32333870 DOI: 10.1016/s2213-8587(20)30121-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 03/30/2020] [Indexed: 01/29/2023]
Affiliation(s)
- Suvi M Virtanen
- Department of Public Health Solutions, Finnish Institute for Health and Welfare FI-00271, Helsinki, Finland; Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland; Tampere University Hospital, Research, Development and Innovation Center, Tampere, Finland; Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.
| | - Mikael Knip
- Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland; Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland
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Smew AI, Lundholm C, Sävendahl L, Lichtenstein P, Almqvist C. Familial Coaggregation of Asthma and Type 1 Diabetes in Children. JAMA Netw Open 2020; 3:e200834. [PMID: 32163166 PMCID: PMC7068230 DOI: 10.1001/jamanetworkopen.2020.0834] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
IMPORTANCE The association between atopic and autoimmune disease, particularly asthma and type 1 diabetes, has been debated. Further understanding of the underlying factors associated with the comorbidity in children is warranted. OBJECTIVES To assess the bidirectional association between asthma and type 1 diabetes and examine the possibility of a shared risk for the diseases by studying their pattern of familial coaggregation. DESIGN, SETTING, AND PARTICIPANTS A birth cohort study of children born from January 1, 2001, and followed up until December 31, 2015, was performed. Population data were obtained from multiple national Swedish registers. A total of 1 347 901 singleton children, live-born in Sweden between January 1, 2001, and December 31, 2013, were identified, and children with incomplete data were excluded. The remaining 1 284 748 children were linked to their biological full siblings, maternal and paternal half-siblings, cousins, and half-cousins. Data analysis was conducted from April 1, 2019, to January 17, 2020. MAIN OUTCOMES AND MEASURES Cases of asthma and type 1 diabetes were defined using a combination of diagnoses and medication prescriptions found in the registers. RESULTS In the cohort of 1 284 748 children, 660 738 children (51.4%) were boys; 121 809 children (9.5%) had asthma, 3812 children (0.3%) had type 1 diabetes, and 494 children had both asthma and type 1 diabetes, representing 0.4% of all asthma or 13% of all type 1 diabetes. Mean (SD) age at diagnosis was 3.0 (2.8) years for children with asthma, and 5.9 (3.3) years for those with type 1 diabetes. Asthma and type 1 diabetes were associated within individuals (odds ratio, 1.15; 95% CI, 1.05-1.27). Children with asthma had an increased risk of subsequent type 1 diabetes (hazard ratio, 1.16; 95% CI, 1.06-1.27); however, subsequent asthma risk did not differ substantially among children with type 1 diabetes (hazard ratio, 0.92; 95% CI, 0.75-1.12). Siblings of individuals with asthma were at an increased risk of type 1 diabetes (odds ratio, 1.27; 95% CI, 1.13-1.42) and vice versa. The results remained positive after controlling for the direct association of one disease with the other. CONCLUSIONS AND RELEVANCE This study appears to provide evidence for co-occurrence, importance of sequential appearance, and coaggregation of asthma and type 1 diabetes in children and their siblings. The findings may suggest shared familial factors contributing to the associations. Knowledge of the nature of the association could be of importance in future clinical practice.
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Affiliation(s)
- Awad I. Smew
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Cecilia Lundholm
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Lars Sävendahl
- Pediatric Endocrinology Unit at Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden
| | - Paul Lichtenstein
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Catarina Almqvist
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden
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Abstract
Diabetes mellitus is a chronic, progressive, incompletely understood metabolic disorder whose prevalence has been increasing steadily worldwide. Even though little attention has been paid to lung disorders in the context of diabetes, its prevalence has recently been challenged by newer studies of disease development. In this review, we summarize and discuss the role of diabetes mellitus involved in the progression of pulmonary diseases, with the main focus on pulmonary fibrosis, which represents a chronic and progressive disease with high mortality and limited therapeutic options.
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Affiliation(s)
- Saeed Kolahian
- Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), Eberhard Karls University Hospitals and Clinics, Tübingen, Germany.
- Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Tübingen, Germany.
- Department of Pharmacogenomics, University of Tübingen, Wilhelmstrasse. 56, D-72074, Tübingen, Germany.
| | - Veronika Leiss
- Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), Eberhard Karls University Hospitals and Clinics, Tübingen, Germany
| | - Bernd Nürnberg
- Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), Eberhard Karls University Hospitals and Clinics, Tübingen, Germany
- Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Tübingen, Germany
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