|
1
|
Özel A, Erol EE, Yüce S, Büke Ö, Tahmiscioglu F, Erol M. Deciphering the role of lactate as a prognostic indicator in pediatric diabetic ketoacidosis. Wien Klin Wochenschr 2025; 137:98-104. [PMID: 39259222 DOI: 10.1007/s00508-024-02428-z] [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: 06/12/2024] [Accepted: 08/07/2024] [Indexed: 09/12/2024]
Abstract
INTRODUCTION Serum lactate levels have been recognized as a robust marker for predicting disease severity and survival in many critically ill children but consensus is lacking regarding its utility in diabetic ketoacidosis. This study aimed to investigate the relationship between initial lactate levels and disease severity in pediatric patients presenting with diabetic ketoacidosis. METHODS This single-center retrospective descriptive study involved pediatric patients with diabetic ketoacidosis in the pediatric emergency department between January 2022 and April 2023. Patients were diagnosed using the International Society for Pediatric and Adolescent Diabetes 2022 guidelines. RESULTS Among the 112 patients included in the study, 41 (36.6%) were classified as mild, 42 (34.8%) as moderate and 32 (28.6%) as severe acidosis. A statistically significant difference was observed between the time to resolution and clinical severity of diabetic ketoacidosis (p < 0.001). Elevated lactate levels of 2.5 mmol/L or above were detected in 37.5% (42/112) of our patients and a significant increase in clinical severity was observed as lactate levels increased (p < 0.001). Correlation analysis revealed no significant relationship between lactate levels and time to resolution of diabetic ketoacidosis or length of intensive care unit stay. Multivariate analysis demonstrated a significant association between lactate levels and severity of acidosis (p: 0.046). CONCLUSION Although there is an association between the severity of acidosis and lactate levels in diabetic ketoacidosis, contrary to expectations, this relationship was not found to be associated with adverse outcomes. An important point not to be overlooked by pediatricians is that elevated lactate levels in diabetic ketoacidosis may not always herald poor outcomes.
Collapse
Affiliation(s)
- Abdulrahman Özel
- Bagcılar Training and Research Hospital, Department of Pediatrics, Pediatric Intensive Care Unit, Health Sciences University Turkey, Istanbul, Turkey.
| | - Esra Ecem Erol
- Bagcılar Training and Research Hospital, Department of Pediatrics, Health Sciences University Turkey, Istanbul, Turkey
| | - Servet Yüce
- Istanbul Faculty of Medicine, Department of Public Health, Istanbul University, Istanbul, Turkey
| | - Övgü Büke
- Bagcılar Training and Research Hospital, Department of Pediatrics, Health Sciences University Turkey, Istanbul, Turkey
| | - Feride Tahmiscioglu
- Bağcılar Training and Research Hospital, Department of Pediatric Endocrinology, Health Sciences University Turkey, Istanbul, Turkey
| | - Meltem Erol
- Bagcılar Training and Research Hospital, Department of Pediatrics, Health Sciences University Turkey, Istanbul, Turkey
| |
Collapse
|
|
2
|
AlMoosa ES, Al Ghadeer HA, Alatiya JE, Aldairam WH, Alhamrani AM, Alarbash AA, Alamer AT, AlHelal MT, Alkhawajah AM, AlDaif ZY, Alarab YA, Al Hani MF, Alhamdan AY, AlWassel AI, Alshabaan AA. The Prevalence of Autoimmune Diseases Among Children With Type I Diabetes Mellitus. Cureus 2024; 16:e76272. [PMID: 39845243 PMCID: PMC11753791 DOI: 10.7759/cureus.76272] [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] [Accepted: 12/01/2024] [Indexed: 01/24/2025] Open
Abstract
Background Type I diabetes mellitus (T1DM) is a prevalent chronic illness that typically manifests in childhood. In patients who are genetically predisposed to diabetes, complex interactions between environmental and genetic factors play a role in the development of type 1 diabetes. There is proof that the onset of type 1 diabetes raises the possibility of developing additional autoimmune conditions. This has to do with the hereditary predisposition to these illnesses. As the autoimmune process in pancreatic beta cells advances, it may also impact other organs, leading to the emergence of autoimmune diseases that are either organ-specific or organ-nonspecific. Purpose The purpose of this study is to determine the prevalence of autoimmune disorders among children who are diagnosed with T1DM in Al-Ahsa, Saudi Arabia, and assess the potential impact of these conditions on other comorbidities. Methods Over the course of three years, from 2020 to 2023, children with T1DM were the subjects of this descriptive retrospective cross-sectional study conducted in the Endocrinology and Diabetes Unit of the Maternity and Children's Hospital in Al-Ahsa, Saudi Arabia. There were 281 participants in total. Clinical and laboratory research was conducted on autoimmune T1DM. Results A total of 281 T1DM children were investigated, with 59.9% being female and 43.1% being male. The mean age was 12.8 ± 3.3 years, and the mean disease duration at the end of follow-up was 6.6 ± 2.9 years. Among these participants, 5.3% were diagnosed with at least one autoimmune disease (AID). Celiac disease is the most commonly reported AID, accounting for 56.3%, followed by hypothyroidism (31.3%). An increased risk of developing AIDs was linked to significant associations between older age (>10 years old) and longer duration of DM (p<0.05). Conclusion The data show a high prevalence of autoimmune comorbidities among pediatric T1DM patients treated at our department. The findings highlight the importance of regular screenings in facilitating timely diagnosis and intervention, which is critical in promoting the well-being and normative development of pediatric patients.
Collapse
Affiliation(s)
- Eman S AlMoosa
- Paediatrics, Maternity and Children Hospital, Al-Ahsa, SAU
| | | | | | | | | | | | - Ali T Alamer
- Paediatrics, Maternity and Children Hospital, Al-Ahsa, SAU
| | | | | | | | - Yaser A Alarab
- Paediatrics, Maternity and Children Hospital, Al-Ahsa, SAU
| | | | | | | | | |
Collapse
|
|
3
|
Zhang Z, Wang X, Dong W, Gao D. Parental care experience of children with type 1 diabetes: a qualitative meta-synthesis. Rev Esc Enferm USP 2024; 58:e20240118. [PMID: 39589154 PMCID: PMC11584163 DOI: 10.1590/1980-220x-reeusp-2024-0118en] [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: 04/25/2024] [Accepted: 08/26/2024] [Indexed: 11/27/2024] Open
Abstract
OBJECTIVE To assess qualitative studies on parents' caregiving experiences whose children have T1DM and develop personalized support strategies based on the findings. METHOD A systematic review with meta-synthesis performed in the Cochrane Library, Embase, Scopus, CINAHL, PubMed, Web of Science, CNKI, CBM, VIP, and Wanfang databases. Quality was assessed via the JBI criteria, and meta-aggregative method was applied to categorize the results into subtopics and aggregate into three interrelated meta-topics to understand parents' caregiving experiences. RESULTS In total, 2,100 articles were found, out of which 15 were selected and analyzed. The identified three meta-topics were "Parents facing multiple physical, mental and life challenges", "Parents' lack of a full range of external support" and "Parents' caregiving role competency enhanced to adjust to the new life". CONCLUSION it is critical for healthcare professionals to recognize these parental experiences and offer targeted knowledge, skills training, and psychological support tailored to their needs, including group training, online mindfulness interventions, and improved empathy from the medical team.
Collapse
Affiliation(s)
- Zhaoying Zhang
- Zhengzhou University, School of Nursing and Health, Zhengzhou, China
| | - Xin Wang
- Zhengzhou University, School of Nursing and Health, Zhengzhou, China
| | - Wenwen Dong
- Zhengzhou University, School of Nursing and Health, Zhengzhou, China
| | - Danshan Gao
- Zhengzhou University, School of Nursing and Health, Zhengzhou, China
| |
Collapse
|
|
4
|
Wu H, Huo H, Li H, Zhang H, Li X, Han Q, Liao J, Tang Z, Guo J. N-acetylcysteine combined with insulin therapy can reduce myocardial injury induced by type 1 diabetes through the endoplasmic reticulum pathway. Tissue Cell 2024; 90:102515. [PMID: 39146674 DOI: 10.1016/j.tice.2024.102515] [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: 03/20/2024] [Revised: 07/17/2024] [Accepted: 08/02/2024] [Indexed: 08/17/2024]
Abstract
With the development of Type 1 diabetes mellitus (T1DM), various complications can be caused. Hyperglycemia affects the microenvironment of cardiomyocytes, changes endoplasmic reticulum homeostasis, triggers unfolding protein response and eventually promotes myocardial apoptosis. However, insulin therapy alone cannot effectively combat the complications caused by T1DM. Forty adult beagles were randomly divided into five groups: control group, diabetes mellitus group, insulin group, insulin combined with NAC group, and NAC group. 24-hour blood glucose, 120-day blood glucose, 120-day body weight, and serum FMN content were observed, furthermore, hematoxylin-eosin staining, Periodic acid Schiff reagent staining, and Sirius red staining of the myocardium were evaluated. The protein expressions of GRP78, ATF6, IRE1, PERK, JNK, CHOP, caspase 3, Bcl2, and Bax were detected. Results of the pathological section of myocardial tissue indicated that insulin combined with NAC therapy could improve myocardial pathological injury and glycogen deposition. Additionally, insulin combined with NAC therapy down-regulates the expression of GRP78, ATF6, IRE1, PERK, JNK, CHOP, caspase3, and Bax. These findings suggest that NAC has a phylactic effect on myocardial injury in beagles with T1DM, and the mechanism may be related to the improvement of endoplasmic reticulum stress-induced apoptosis.
Collapse
Affiliation(s)
- Haitong Wu
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
| | - Haihua Huo
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
| | - Haoye Li
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
| | - Hongyan Zhang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
| | - Xinrun Li
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
| | - Qingyue Han
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
| | - Jianzhao Liao
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
| | - Zhaoxin Tang
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
| | - Jianying Guo
- College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
| |
Collapse
|
|
5
|
Yoo J, Hwang J, Choi J, Ramalingam M, Jeong H, Jang S, Jeong HS, Kim D. The effects of resistance training on cardiovascular factors and anti-inflammation in diabetic rats. Heliyon 2024; 10:e37081. [PMID: 39295999 PMCID: PMC11407942 DOI: 10.1016/j.heliyon.2024.e37081] [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: 06/23/2024] [Revised: 08/25/2024] [Accepted: 08/27/2024] [Indexed: 09/21/2024] Open
Abstract
Diabetes induces a range of macrovascular and microvascular changes, which lead to significant clinical complications. Although many studies have tried to solve the diabetic problem using drugs, it remains unclear. In this study, we investigated whether resistance exercise affects cardiovascular factors and inflammatory markers in diabetes. The study subjected Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which have genetically induced diabetes mellitus, to a resistance exercise program for 12 weeks and assessed the levels of cardiovascular factors and inflammatory markers using western blotting analysis, ELISA, and immunohistochemistry. During the training period, OLETF + exercise (EX) group exhibited lower body weight and reduced glucose levels when compared with OLETF group. Western blotting analysis, ELISA, and immunohistochemistry revealed that the levels of PAI-1, VACM-1, ICAM-1, E-selectin, TGF-β, CRP, IL-6, and TNF-α were decreased in OLETF + EX group when compared with the OLETF group. Moreover, the anti-inflammatory markers, IL-4 and IL-10, were highly expressed after exercise. Therefore, these results indicate that exercise may influence the regulation of cardiovascular factors and inflammatory markers, as well as help patients with metabolic syndromes regulate inflammation and cardiovascular function.
Collapse
Affiliation(s)
- Jin Yoo
- Department of Physical Education, Chonnam National University, Gwangju, 61186, Republic of Korea
| | - Jinsu Hwang
- Department of Physiology, Chonnam National University Medical School, Hwasun-gun, Jeollanamdo, 58128, Republic of Korea
| | - Jiyun Choi
- Department of Physiology, Chonnam National University Medical School, Hwasun-gun, Jeollanamdo, 58128, Republic of Korea
| | - Mahesh Ramalingam
- Department of Physiology, Chonnam National University Medical School, Hwasun-gun, Jeollanamdo, 58128, Republic of Korea
| | - Haewon Jeong
- StemCell Bio Incorporated, Hwasun-gun, Jeollanamdo, 58128, Republic of Korea
| | - Sujeong Jang
- Department of Physiology, Chonnam National University Medical School, Hwasun-gun, Jeollanamdo, 58128, Republic of Korea
- StemCell Bio Incorporated, Hwasun-gun, Jeollanamdo, 58128, Republic of Korea
| | - Han-Seong Jeong
- Department of Physiology, Chonnam National University Medical School, Hwasun-gun, Jeollanamdo, 58128, Republic of Korea
- StemCell Bio Incorporated, Hwasun-gun, Jeollanamdo, 58128, Republic of Korea
| | - Daeyeol Kim
- Department of Physical Education, Chonnam National University, Gwangju, 61186, Republic of Korea
| |
Collapse
|
|
6
|
Nag S, Stany B, Mishra S, Kumar S, Mohanto S, Ahmed MG, Mathew B, Subramaniyan V. Multireceptor Analysis for Evaluating the Antidiabetic Efficacy of Karanjin: A Computational Approach. Endocrinol Diabetes Metab 2024; 7:e509. [PMID: 38982323 PMCID: PMC11233261 DOI: 10.1002/edm2.509] [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: 05/21/2024] [Revised: 06/15/2024] [Accepted: 06/23/2024] [Indexed: 07/11/2024] Open
Abstract
BACKGROUND Diabetes mellitus, notably type 2, is a rising global health challenge, prompting the need for effective management strategies. Common medications such as metformin, insulin, repaglinide and sitagliptin can induce side effects like gastrointestinal disturbances, hypoglycemia, weight gain and specific organ risks. Plant-derived therapies like Karanjin from Pongamia pinnata present promising alternatives due to their historical use, holistic health benefits and potentially fewer adverse effects. This study employs in silico analysis to explore Karanjin's interactions with diabetes-associated receptors, aiming to unveil its therapeutic potential while addressing the limitations and side effects associated with conventional medications. METHODOLOGY The research encompassed the selection of proteins from the Protein Data Bank (PDB), followed by structural refinement processes and optimization. Ligands such as Karanjin and standard drugs were retrieved from PubChem, followed by a comprehensive analysis of their ADMET profiling and pharmacokinetic properties. Protein-ligand interactions were evaluated through molecular docking using AutoDockTools 1.5.7, followed by the analysis of structural stability using coarse-grained simulations with CABS Flex 2.0. Molecular dynamics simulations were performed using Desmond 7.2 and the OPLS4 force field to explore how Karanjin interacts with proteins over 100 nanoseconds, focusing on the dynamics and structural stability. RESULTS Karanjin, a phytochemical from Pongamia pinnata, shows superior drug candidate potential compared to common medications, offering advantages in efficacy and reduced side effects. It adheres to drug-likeness criteria and exhibits optimal ADMET properties, including moderate solubility, high gastrointestinal absorption and blood-brain barrier penetration. Molecular docking revealed Karanjin's highest binding energy against receptor 3L2M (Pig pancreatic alpha-amylase) at -9.1 kcal/mol, indicating strong efficacy potential. Molecular dynamics simulations confirmed stable ligand-protein complexes with minor fluctuations in RMSD and RMSF, suggesting robust interactions with receptors 3L2M. CONCLUSION Karanjin demonstrates potential in pharmaceutical expansion for treating metabolic disorders such as diabetes, as supported by computational analysis. Prospects for Karanjin in pharmaceutical development include structural modifications for enhanced efficacy and safety. Nanoencapsulation may improve bioavailability and targeted delivery to pancreatic cells, while combination therapies could optimize treatment outcomes in diabetes management. Clinical trials and experimental studies are crucial to validate its potential as a novel therapeutic agent.
Collapse
Affiliation(s)
- Sagnik Nag
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia
| | - B Stany
- Department of Biomedical Sciences, School of Bio-Sciences & Technology (SBST), Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India
| | - Shatakshi Mishra
- Department of Biomedical Sciences, School of Bio-Sciences & Technology (SBST), Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India
| | - Sunil Kumar
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, India
| | - Sourav Mohanto
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to Be University), Mangalore, Karnataka, India
| | - Mohammed Gulzar Ahmed
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to Be University), Mangalore, Karnataka, India
| | - Bijo Mathew
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, India
| | - Vetriselvan Subramaniyan
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia
| |
Collapse
|
|
7
|
Celis-Andrade M, Morales-González V, Rojas M, Monsalve DM, Acosta-Ampudia Y, Rodríguez-Jiménez M, Rodríguez Y, Ramírez-Santana C. Prevalence of latent and overt polyautoimmunity in type 1 diabetes: A systematic review and meta-analysis. Diabetes Metab Syndr 2024; 18:103087. [PMID: 39074403 DOI: 10.1016/j.dsx.2024.103087] [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: 02/28/2024] [Revised: 07/15/2024] [Accepted: 07/20/2024] [Indexed: 07/31/2024]
Abstract
BACKGROUND Patients afflicted by type 1 diabetes (T1D) exhibit polyautoimmunity (PolyA). However, the frequency and distribution of PolyA in T1D is still unknown. OBJECTIVE We conducted a systematic review and meta-analysis to define the prevalence of latent and overt PolyA in individuals with T1D. METHODS Following PRISMA guidelines, a comprehensive search across medical databases identified studies on latent and overt PolyA in T1D. Two researchers independently screened, extracted data, and assessed study quality. A random effects model was utilized to calculate the pooled prevalence, along with its corresponding 95 % confidence interval (CI), for latent PolyA and overt PolyA. Meta-regression analysis was conducted to study the effect of study designs, age, sex, and duration of disease on pooled prevalence. RESULTS A total of 158 articles, encompassing a diverse composition of study designs were scrutinized. The analysis included 270,890 individuals with a confirmed diagnosis of T1D. The gender was evenly distributed (50.30 % male). Notably, our analysis unveiled an overt PolyA prevalence rate of 8.50 % (95 % CI, 6.77 to 10.62), with North America having the highest rates (14.50 %, 95 % CI, 7.58 to 24.89). This PolyA profile was further characterized by a substantial incidence of concurrent autoimmune thyroid disease (7.44 %, 95 % CI, 5.65 to 9.74). Moreover, we identified a notable prevalence of latent PolyA in the T1D population, quantified at 14.45 % (95 % CI, 11.17 to 18.49) being most frequent in Asia (23.29 %, 95 % CI, 16.29 to 32.15) and Oceania (21.53 %, 95 % CI, 16.48 to 27.62). Remarkably, this latent PolyA phenomenon primarily featured an array of autoantibodies, including rheumatoid factor, followed by Ro52, thyroid peroxidase antibodies, and thyroglobulin antibodies. Duration of the disease was associated with a highest frequency of latent (β: 0.0456, P-value: 0.0140) and overt PolyA (β: 0.0373, P-value: 0.0152). No difference in the pooled prevalence by study design was observed. CONCLUSION This meta-analysis constitutes a substantial advancement in the realm of early detection of PolyA in the context of T1D. Individuals with T1D should regularly undergo assessments to identify potential concurrent autoimmune diseases, especially as they age.
Collapse
Affiliation(s)
- Mariana Celis-Andrade
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá D.C., Colombia
| | - Victoria Morales-González
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá D.C., Colombia
| | - Manuel Rojas
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá D.C., Colombia; Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, 95616, USA
| | - Diana M Monsalve
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá D.C., Colombia
| | - Yeny Acosta-Ampudia
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá D.C., Colombia
| | - Mónica Rodríguez-Jiménez
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá D.C., Colombia
| | - Yhojan Rodríguez
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá D.C., Colombia; Department of Internal Medicine, University Hospital, Fundación Santa Fe de Bogotá, Bogotá D.C., Colombia
| | - Carolina Ramírez-Santana
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad Del Rosario, Bogotá D.C., Colombia.
| |
Collapse
|
|
8
|
He R, Chen Y. The Role of Adipose Tissue-derived Exosomes in Chronic Metabolic Disorders. Curr Med Sci 2024; 44:463-474. [PMID: 38900388 DOI: 10.1007/s11596-024-2902-2] [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: 11/08/2023] [Accepted: 05/28/2024] [Indexed: 06/21/2024]
Abstract
Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases, such as type 2 diabetes mellitus (T2DM), cardiovascular diseases, and non-alcoholic fatty liver disease (NAFLD). Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles (EVs) that play a role in the regulation of whole-body metabolism. Exosomes are a subtype of EVs, and accumulating evidence indicates that adipose tissue exosomes (AT Exos) mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms. However, the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated. In this review, we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders. Moreover, we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.
Collapse
Affiliation(s)
- Rui He
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Laboratory of Endocrinology & Metabolism, Key Laboratory of Vascular Aging of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yong Chen
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Laboratory of Endocrinology & Metabolism, Key Laboratory of Vascular Aging of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, China.
| |
Collapse
|
|
9
|
Shen J, Qin H, Li K, Ding H, Chen X, Peng M, Jiang X, Han Y. The angelica Polysaccharide: a review of phytochemistry, pharmacology and beneficial effects on systemic diseases. Int Immunopharmacol 2024; 133:112025. [PMID: 38677093 DOI: 10.1016/j.intimp.2024.112025] [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: 01/09/2024] [Revised: 04/02/2024] [Accepted: 04/04/2024] [Indexed: 04/29/2024]
Abstract
Angelica sinensis is a perennial herb widely distributed around the world, and angelica polysaccharide (APS) is a polysaccharide extracted from Angelica sinensis. APS is one of the main active components of Angelica sinensis. A large number of studies have shown that APS has hematopoietic, promoting blood circulation, radiation resistance, lowering blood glucose, enhancing the body immunity and other pharmacological effects in a variety of diseases. However, different extraction methods and extraction sites greatly affect the efficacy of APS. In recent years, with the emerging of new technologies, there are more and more studies on the combined application and structural modification of APS. In order to promote the comprehensive development and in-depth application of APS, this narrative review systematically summarizes the effects of different drying methods and extraction sites on the biological activity of APS, and the application of APS in the treatment of diseases, hoping to provide a scientific basis for the experimental study and clinical application of APS.
Collapse
Affiliation(s)
- Jie Shen
- School of Pharmacy, Qingdao University, Qingdao, China
| | - Huan Qin
- School of Basic Medical Sciences, Qingdao, China
| | - Kangkang Li
- School of Basic Medical Sciences, Qingdao, China
| | - Huiqing Ding
- School of Basic Medical Sciences, Qingdao, China.
| | - Xuehong Chen
- School of Basic Medical Sciences, Qingdao, China.
| | - Meiyu Peng
- School of Basic Medical Sciences, Shandong Second Medical University, China
| | - Xin Jiang
- School of Basic Medical Sciences, Qingdao, China.
| | - Yantao Han
- School of Basic Medical Sciences, Qingdao, China.
| |
Collapse
|
|
10
|
Kawasaki E, Tamai H, Fukuyama T, Sagara Y, Hidaka R, Uchida A, Tojikubo M, Tatsumoto N, Akehi Y, Hiromatsu Y. Enzyme-linked immunosorbent assay of 3 Screen Islet Cell Autoantibody in patients with autoimmune thyroid disease. World J Diabetes 2024; 15:935-944. [PMID: 38766435 PMCID: PMC11099373 DOI: 10.4239/wjd.v15.i5.935] [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: 01/27/2024] [Revised: 02/07/2024] [Accepted: 03/11/2024] [Indexed: 05/10/2024] Open
Abstract
BACKGROUND In recent years, the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes (T1D). While it has been established that 20%-30% of T1D patients suffer from autoimmune thyroid disease (AITD), there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients. Among commercially available anti-islet autoantibodies, glutamic acid decarboxylase 65 autoantibodies (GADAs) are often the first marker measured in general clinical practice. AIM To investigate the frequency of anti-islet autoantibodies in AITD patients. METHODS Our study involved four hundred ninety-five AITD patients, categorized into three distinct groups: AITD with T1D (n = 18), AITD with phenotypic type 2 diabetes (T2D) (n = 81), and AITD without diabetes (n = 396), and the enzyme-linked immunosorbent assay (ELISA) was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody (3 Screen ICA), GADA, insulinoma-associated antigen-2 autoantibodies (IA-2As), and zinc transporter 8 autoantibodies (ZnT8As) within these groups. RESULTS The frequency of 3 Screen ICA in AITD patients with T1D, T2D, and those without diabetes were 88.9%, 6.2%, and 5.1%, respectively, with no significant difference seen between the latter two groups. Notably, the frequency of 3 Screen ICA was 11.1% higher in AITD patients with T1D, 1.3% higher in AITD patients with T2D, and 1.1% higher in AITD patients without diabetes compared to GADA, respectively. Furthermore, 12.5%, 20.0%, and 20.0% of the 3 Screen ICA-positive patients were negative for GADA. Additionally, 1.3% of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies. Among the 3 Screen ICA-positive patients, there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes (37.5% vs 5.0%, P < 0.05). However, this proportion was similar to that in AITD patients with T2D (20.0%). Nevertheless, there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes (436.8 ± 66.4 vs 308.1 ± 66.4 index). Additionally, no significant difference in 3 Screen ICA titers was observed between Graves' disease and Hashimoto's thyroiditis in any of the groups. CONCLUSION Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D. Thus, 3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.
Collapse
Affiliation(s)
- Eiji Kawasaki
- The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, Kurume 830-8577, Japan
| | - Hidekazu Tamai
- The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, Kurume 830-8577, Japan
| | - Takahiro Fukuyama
- The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, Kurume 830-8577, Japan
| | - Yoko Sagara
- The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, Kurume 830-8577, Japan
| | - Ryutaro Hidaka
- The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, Kurume 830-8577, Japan
| | - Aira Uchida
- The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, Kurume 830-8577, Japan
| | - Masayuki Tojikubo
- The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, Kurume 830-8577, Japan
| | - Narihito Tatsumoto
- The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, Kurume 830-8577, Japan
| | - Yuko Akehi
- The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, Kurume 830-8577, Japan
| | - Yuji Hiromatsu
- The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, Kurume 830-8577, Japan
| |
Collapse
|
|
11
|
Hajaj H, Elouali A, Hamami A, Babakhouya A, Rkain M. Celiac Disease and Autoimmune Diseases in a Pediatric Population in Morocco: A Cross-Sectional Study. Cureus 2024; 16:e61468. [PMID: 38953066 PMCID: PMC11216121 DOI: 10.7759/cureus.61468] [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] [Accepted: 05/31/2024] [Indexed: 07/03/2024] Open
Abstract
INTRODUCTION Celiac disease (CD) is defined as an autoimmune disease (AD) caused by gluten ingestion in genetically sensitive individuals. Several publications have demonstrated the increased risk of AD in patients with CD, both adults and children, which requires systematic research. Our study aimed to determine the prevalence of AD in 60 patients diagnosed with CD and to highlight risk factors that may contribute to the emergence of AD. MATERIALS AND METHODS We collected medical data from all CD patients under 16 years of age who also had AD. Our study was conducted in the Gastroenterology-Hepatology and Pediatric Nutrition Unit of the Pediatrics Department of the Mohamed VI Hospital and University Center in Oujda, Morocco, during a seven-year period between January 2017 and January 2024. RESULTS We studied 60 patients with CD in our study. Eight patients (13%) had an associated AD. Their average age was eight years, with extremes varying between two and 15 years. AD was diagnosed before CD in six cases (75%), in parallel with CD in one patient (12.5%), while in only one case, it was diagnosed after CD (12.5%). All our patients had a single AD associated with CD. These ADs were mainly type 1 diabetes in seven cases and autoimmune thyroiditis in only one case. All our patients followed a gluten-free diet in addition to specific treatment for associated AD. Nevertheless, despite regular medical follow-up and targeted dietary advice for the management of CD and associated AD, three patients encountered difficulties in following the recommended diet. CONCLUSION Younger patients with CD have an increased risk of hypothyroidism and insulin-dependent diabetes. These data necessitate improved surveillance to discover these illnesses as early as possible in order to optimize management and reduce related consequences.
Collapse
Affiliation(s)
- Hanane Hajaj
- Department of Pediatrics, University Hospital Mohammed VI, Faculty of Medicine and Pharmacy, Mother and Child Health Laboratory, Mohammed First University, Oujda, MAR
| | - Aziza Elouali
- Department of Pediatrics, University Hospital Mohammed VI, Faculty of Medicine and Pharmacy, Mother and Child Health Laboratory, Mohammed First University, Oujda, MAR
| | - Amal Hamami
- Department of Pediatrics, University Hospital Mohammed VI, Faculty of Medicine and Pharmacy, Mother and Child Health Laboratory, Mohammed First University, Oujda, MAR
| | - Abdeladim Babakhouya
- Department of Pediatrics, University Hospital Mohammed VI, Faculty of Medicine and Pharmacy, Mother and Child Health Laboratory, Mohammed First University, Oujda, MAR
| | - Maria Rkain
- Department of Pediatrics, University Hospital Mohammed VI, Faculty of Medicine and Pharmacy, Mother and Child Health Laboratory, Mohammed First University, Oujda, MAR
| |
Collapse
|
|
12
|
Samuelsson J, Bertilsson R, Bülow E, Carlsson S, Åkesson S, Eliasson B, Hanas R, Åkesson K. Autoimmune comorbidity in type 1 diabetes and its association with metabolic control and mortality risk in young people: a population-based study. Diabetologia 2024; 67:679-689. [PMID: 38252314 PMCID: PMC10904419 DOI: 10.1007/s00125-024-06086-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 11/27/2023] [Indexed: 01/23/2024]
Abstract
AIMS/HYPOTHESIS This register-based study aimed to describe autoimmune comorbidity in children and young adults from type 1 diabetes onset, and to investigate whether such comorbidity was associated with a difference in HbA1c or mortality risk compared with children/young adults with type 1 diabetes without autoimmune comorbidity. METHODS A total of 15,188 individuals from the Swedish National Diabetes Register, registered with type 1 diabetes before 18 years of age between 2000 and 2019, were included. Five randomly selected control individuals from the Swedish population (Statistics Sweden) were matched to each individual with type 1 diabetes (n=74,210 [346 individuals with type 1 diabetes were not found in the Statistics Sweden register at the date of type 1 diabetes diagnosis, so could not be matched to control individuals]). The National Patient Register was used to attain ICD-10 codes on autoimmune diseases and the Cause of Death Register was used to identify deceased individuals. RESULTS In the total type 1 diabetes cohort, mean±SD age at onset of type 1 diabetes was 9.5±4.4 years and mean disease duration at end of follow-up was 8.8±5.7 years. Of the individuals with type 1 diabetes, 19.2% were diagnosed with at least one autoimmune disease vs 4.0% of the control group. The HRs for comorbidities within 19 years from onset of type 1 diabetes were 11.6 (95% CI 10.6, 12.6) for coeliac disease, 10.6 (95% CI 9.6, 11.8) for thyroid disease, 1.3 (95% CI 1.1, 1.6) for psoriasis, 4.1 (95% CI 3.2, 5.3) for vitiligo, 1.7 (95% CI 1.4, 2.2) for rheumatic joint disease, 1.0 (95% CI 0.8, 1.3) for inflammatory bowel disease, 1.0 (95% CI 0.7, 1.2) for systemic connective tissue disorder, 1.4 (95% CI 1.1, 1.9) for uveitis, 18.3 (95% CI 8.4, 40.0) for Addison's disease, 1.8 (95% CI 0.9, 3.6) for multiple sclerosis, 3.7 (95% CI 1.6, 8.7) for inflammatory liver disease and 19.6 (95% CI 4.2, 92.3) for atrophic gastritis. Autoimmune disease in addition to type 1 diabetes had no statistically significant effect on HbA1c or mortality risk. CONCLUSIONS/INTERPRETATION To our knowledge, this is the first comprehensive study where young individuals with type 1 diabetes were followed regarding development of a wide spectrum of autoimmune diseases, from onset of type 1 diabetes. In this nationwide and population-based study, there was already a high prevalence of autoimmune diseases in childhood, especially coeliac and thyroid disease. The presence of autoimmune comorbidity did not have a statistically significant effect on metabolic control or mortality risk.
Collapse
Affiliation(s)
- John Samuelsson
- Department of Paediatrics, Ryhov County Hospital, Jönköping, Sweden.
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
| | | | - Erik Bülow
- Centre of Registers in Region Västra Götaland, Gothenburg, Sweden
- Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Sanna Carlsson
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Sanna Åkesson
- The Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Björn Eliasson
- Centre of Registers in Region Västra Götaland, Gothenburg, Sweden
- Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Ragnar Hanas
- The Sahlgrenska Academy, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden
- Department of Paediatrics, NU Hospital Group, Uddevalla, Sweden
| | - Karin Åkesson
- Department of Paediatrics, Ryhov County Hospital, Jönköping, Sweden.
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
| |
Collapse
|
|
13
|
Li K, Ouyang Y, Yang H. Myasthenia gravis and five autoimmune diseases: a bidirectional Mendelian randomization study. Neurol Sci 2024; 45:1699-1706. [PMID: 37910321 DOI: 10.1007/s10072-023-07163-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 10/18/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND The association between myasthenia gravis (MG) and other autoimmune diseases is well established. In this study, we aimed to investigate the causal effects between MG and five other autoimmune diseases, including autoimmune thyroid disease (AITD), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and type 1 diabetes (T1DM). METHODS We conducted a bidirectional Mendelian randomization (MR) study by using seven published genome-wide association studies (GWAS), including MG (1873 patients versus 36,370 controls), AITD (autoimmune hypothyroidism) (22,997 patients versus 175,475 controls), AITD (autoimmune hyperthyroidism) (962 patients versus 172,976 controls), MS (47,429 patients versus 68,374 controls), RA (14,361 patients versus 43,923 controls), SLE (4222 patients versus 8431 controls), and T1DM (9266 patients versus 15,574 controls). We used the inverse-variance-weighted (IVW) method, weighted-median (WM) estimator, MR-Egger regression, and MR PRESSO in our analyses. We also carried out detailed sensitivity analyses for each direction using the aforementioned methods. RESULTS When MG was treated as the exposure, MR evidence suggested a causal relationship between MG and T1DM, SLE, AITD (both hypothyroidism and hyperthyroidism), and MS (excluding RA). Using the IVW method, we found that MG was associated with increased risk of T1DM (OR = 1.94; 95% CI, 1.16-3.26; p = 0.012), SLE (OR = 1.47; 95% CI, 1.02-2.13; p = 0.04), AITD (hypothyroidism) (OR = 1.31; 95% CI, 1.02-1.68; p = 0.039), AITD (hyperthyroidism) (OR = 1.55; 95% CI, 1.15-2.09; p = 0.004), and MS (OR = 1.46; 95% CI, 1.01-2.09; p = 0.041). When MG was treated as the outcome, MR evidence suggested that RA, T1DM, and SLE were causal factors in MG. Using the IVW method, we found that the risk of MG increased with exposure to RA (OR = 1.21; 95% CI, 1.08-1.37; p = 0.002), T1DM (OR = 1.09; 95% CI, 1.02-1.16; p = 0.006), and SLE (OR = 1.12; 95% CI, 1.02-1.23; p = 0.018). CONCLUSIONS This study demonstrated a causal relationship between MG and several other autoimmune diseases. Our results supported a bidirectional causal association between MG and SLE/T1DM. Our findings also provided reliable evidence that MG is associated with increased risk of AITD. Meanwhile, we also showed that RA is a possible causal driver of MG risk.
Collapse
Affiliation(s)
- Kailin Li
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Yuzhen Ouyang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Huan Yang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410013, China.
| |
Collapse
|
|
14
|
Ko J, Song J, Choi N, Kim HN. Patient-Derived Microphysiological Systems for Precision Medicine. Adv Healthc Mater 2024; 13:e2303161. [PMID: 38010253 PMCID: PMC11469251 DOI: 10.1002/adhm.202303161] [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: 11/06/2023] [Indexed: 11/29/2023]
Abstract
Patient-derived microphysiological systems (P-MPS) have emerged as powerful tools in precision medicine that provide valuable insight into individual patient characteristics. This review discusses the development of P-MPS as an integration of patient-derived samples, including patient-derived cells, organoids, and induced pluripotent stem cells, into well-defined MPSs. Emphasizing the necessity of P-MPS development, its significance as a nonclinical assessment approach that bridges the gap between traditional in vitro models and clinical outcomes is highlighted. Additionally, guidance is provided for engineering approaches to develop microfluidic devices and high-content analysis for P-MPSs, enabling high biological relevance and high-throughput experimentation. The practical implications of the P-MPS are further examined by exploring the clinically relevant outcomes obtained from various types of patient-derived samples. The construction and analysis of these diverse samples within the P-MPS have resulted in physiologically relevant data, paving the way for the development of personalized treatment strategies. This study describes the significance of the P-MPS in precision medicine, as well as its unique capacity to offer valuable insights into individual patient characteristics.
Collapse
Affiliation(s)
- Jihoon Ko
- Department of BioNano TechnologyGachon UniversitySeongnam‐siGyeonggi‐do13120Republic of Korea
| | - Jiyoung Song
- Brain Science InstituteKorea Institute of Science and Technology (KIST)Seoul02792Republic of Korea
| | - Nakwon Choi
- Brain Science InstituteKorea Institute of Science and Technology (KIST)Seoul02792Republic of Korea
- Division of Bio‐Medical Science & TechnologyKIST SchoolSeoul02792Republic of Korea
- KU‐KIST Graduate School of Converging Science and TechnologyKorea UniversitySeoul02841Republic of Korea
| | - Hong Nam Kim
- Brain Science InstituteKorea Institute of Science and Technology (KIST)Seoul02792Republic of Korea
- Division of Bio‐Medical Science & TechnologyKIST SchoolSeoul02792Republic of Korea
- School of Mechanical EngineeringYonsei UniversitySeoul03722Republic of Korea
- Yonsei‐KIST Convergence Research InstituteYonsei UniversitySeoul03722Republic of Korea
| |
Collapse
|
|
15
|
Antar SA, Ashour NA, Sharaky M, Khattab M, Ashour NA, Zaid RT, Roh EJ, Elkamhawy A, Al-Karmalawy AA. Diabetes mellitus: Classification, mediators, and complications; A gate to identify potential targets for the development of new effective treatments. Biomed Pharmacother 2023; 168:115734. [PMID: 37857245 DOI: 10.1016/j.biopha.2023.115734] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 10/13/2023] [Accepted: 10/13/2023] [Indexed: 10/21/2023] Open
Abstract
Nowadays, diabetes mellitus has emerged as a significant global public health concern with a remarkable increase in its prevalence. This review article focuses on the definition of diabetes mellitus and its classification into different types, including type 1 diabetes (idiopathic and fulminant), type 2 diabetes, gestational diabetes, hybrid forms, slowly evolving immune-mediated diabetes, ketosis-prone type 2 diabetes, and other special types. Diagnostic criteria for diabetes mellitus are also discussed. The role of inflammation in both type 1 and type 2 diabetes is explored, along with the mediators and potential anti-inflammatory treatments. Furthermore, the involvement of various organs in diabetes mellitus is highlighted, such as the role of adipose tissue and obesity, gut microbiota, and pancreatic β-cells. The manifestation of pancreatic Langerhans β-cell islet inflammation, oxidative stress, and impaired insulin production and secretion are addressed. Additionally, the impact of diabetes mellitus on liver cirrhosis, acute kidney injury, immune system complications, and other diabetic complications like retinopathy and neuropathy is examined. Therefore, further research is required to enhance diagnosis, prevent chronic complications, and identify potential therapeutic targets for the management of diabetes mellitus and its associated dysfunctions.
Collapse
Affiliation(s)
- Samar A Antar
- Center for Vascular and Heart Research, Fralin Biomedical Research Institute, Virginia Tech, Roanoke, VA 24016, USA; Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Horus University, New Damietta 34518, Egypt
| | - Nada A Ashour
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt
| | - Marwa Sharaky
- Cancer Biology Department, Pharmacology Unit, National Cancer Institute (NCI), Cairo University, Cairo, Egypt
| | - Muhammad Khattab
- Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Cairo, Egypt
| | - Naira A Ashour
- Department of Neurology, Faculty of Physical Therapy, Horus University, New Damietta 34518, Egypt
| | - Roaa T Zaid
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza 12566, Egypt
| | - Eun Joo Roh
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science & Technology, University of Science and Technology, Daejeon 34113, Republic of Korea
| | - Ahmed Elkamhawy
- BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of Korea; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
| | - Ahmed A Al-Karmalawy
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza 12566, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt
| |
Collapse
|
|
16
|
Odeh R, Gharaibeh L, Ibrahim S, Alassaf A. Associated autoimmune thyroid diseases in children and adolescents with type one diabetes in Jordan. J Pediatr Endocrinol Metab 2023; 36:917-924. [PMID: 37656596 DOI: 10.1515/jpem-2023-0322] [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: 07/06/2023] [Accepted: 08/15/2023] [Indexed: 09/03/2023]
Abstract
OBJECTIVES To investigate the prevalence of thyroid autoimmunity and related thyroid disorders among children and adolescents with type 1 diabetes in Jordan. METHODS In a retrospective study, thyroid stimulating hormone and thyroid hormone (Free T4) levels were measured in 684 children with type 1 diabetes who presented to Jordan University Hospital between January 2012 and February 2021. Anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin (TGAb) antibodies were measured in 526 and 438 subjects with type 1 diabetes, respectively. RESULTS 681 children were included in the study (52.4 % females, average current age 14.3 years, average age at diagnosis 8.0 years, and average diabetes duration 6.2 years). Of the whole group, 18 children (2.6 %) were diagnosed with subclinical hypothyroidism and 31 children (4.4 %) had overt hypothyroidism. Of those who were tested for TPOAb and TGAb, 22.6 and 23.1 % were positive respectively. Predictors for developing hypothyroidism were female sex and positive antibodies to glutamic acid decarboxylase. CONCLUSIONS Screening for associated thyroid autoimmunity in children and adolescents with type one diabetes from Jordan is advised with a special focus on females and those with positive antibodies to glutamic acid decarboxylase.
Collapse
Affiliation(s)
- Rasha Odeh
- Department of Pediatrics, School of Medicine, University of Jordan, Amman, Jordan
| | - Lobna Gharaibeh
- Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, AI-Ahliyya Amman University, Amman, Jordan
| | - Sarah Ibrahim
- Department of Pediatrics, School of Medicine, University of Jordan, Amman, Jordan
| | - Abeer Alassaf
- Department of Pediatrics, School of Medicine, University of Jordan, Amman, Jordan
| |
Collapse
|
|
17
|
Meyers TM, Reeves PT, Lombardo JL, Anisowicz SK, Larson NS, Rogers PL. Autoimmune gastritis as an unexpected cause of diarrhea in a young adult with type I diabetes: a case report. J Med Case Rep 2023; 17:342. [PMID: 37507704 PMCID: PMC10386669 DOI: 10.1186/s13256-023-04039-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 06/13/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND Type 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as: polyuria, polydipsia, polyphagia, and weight loss. Treatment of type 1 diabetes centers on insulin administration to replace or supplement the body's own insulin with the goal of achieving euglycemia and preventing or minimizing complications. Patients with T1DM are at risk for developing other autoimmune conditions, most commonly thyroid or celiac disease. CASE PRESENTATION A 20-year-old African American female with T1DM was referred by her endocrinologist to pediatric gastroenterology for 2 months of nocturnal, non-bloody diarrhea, left lower quadrant pain, and nausea; she was also being followed by neurology for complaints of lower extremity paresthesias and pain. The patient's initial lab-workup was remarkable for a low total Immunoglobulin A (IgA) level of < 6.7 mg/dL. As IgA deficiency is associated with an increased risk of celiac disease, the patient underwent upper and lower endoscopy, which was grossly unremarkable; however, histology revealed a pattern consistent with autoimmune gastritis. Subsequent serum evaluation was remarkable for an elevated fasting gastrin level and an elevated parietal cell antibody level without macrocytic anemia, iron deficiency, or vitamin B12 depletion. The patient was diagnosed with autoimmune gastritis (AIG) and subsequently initiated on parenteral B12 supplementation therapy with improvement in her neurologic and gastrointestinal symptoms. CONCLUSION This case illustrates the importance of recognition of red flag findings in a patient with known autoimmune disease. Following well-established health maintenance recommendations for individuals with T1DM ensures that common comorbidities will be detected. Autoimmune gastritis, while a rarer pathology in the pediatric population, deserves consideration in patients with pre-existing autoimmune conditions and new gastrointestinal or neurologic symptoms, as AIG can be associated with poor outcomes and risk of malignancy. Initial lab findings associated with an eventual diagnosis of AIG typically include anemia, iron deficiency, or Vitamin B12 deficiency. However, as demonstrated in this case, symptoms of AIG can rarely present before anemia or Vitamin B12 deficiency develops. To prevent permanent neurological damage, parenteral Vitamin B12 therapy must be considered even in the absence of Vitamin B12 deficiency, especially in those patients already experiencing neurological symptoms.
Collapse
Affiliation(s)
- Taylor M Meyers
- Department of Pediatrics, Walter Reed National Military Medical Center, 4494 Palmer Road North, Bethesda, MD, 20814, USA.
| | - Patrick T Reeves
- Department of Pediatrics, Walter Reed National Military Medical Center, 4494 Palmer Road North, Bethesda, MD, 20814, USA
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Jamie L Lombardo
- Department of Pediatrics, Walter Reed National Military Medical Center, 4494 Palmer Road North, Bethesda, MD, 20814, USA
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Sarah K Anisowicz
- Department of Pediatrics, Walter Reed National Military Medical Center, 4494 Palmer Road North, Bethesda, MD, 20814, USA
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Noelle S Larson
- Department of Pediatrics, Walter Reed National Military Medical Center, 4494 Palmer Road North, Bethesda, MD, 20814, USA
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Philip L Rogers
- Department of Pediatrics, Walter Reed National Military Medical Center, 4494 Palmer Road North, Bethesda, MD, 20814, USA
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| |
Collapse
|
|
18
|
Girard C, De Percin A, Morin C, Talvard M, Fortenfant F, Congy-Jolivet N, Le Tallec C, Olives JP, Mas E. Accuracy of Serological Screening for the Diagnosis of Celiac Disease in Type 1 Diabetes Children. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1321. [PMID: 37512132 PMCID: PMC10386403 DOI: 10.3390/medicina59071321] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 07/12/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023]
Abstract
Background and Objectives: Patients with type 1 diabetes (T1D) are considered at high-risk for developing celiac disease (CD). The purpose of our study was to determine the prevalence of CD among children who were followed in our unit for T1D using the latest ESPGHAN guidelines, and avoiding intestinal biopsies in some of the children. Materials and Methods: We performed a prospective monocentric study, which included 663 T1D children between June 2014 and June 2016. We considered CD according to serological (tissue transglutaminase (TGAs) and endomysium antibodies) results. Children were included either at the time of T1D diagnosis or during their follow up. We looked for clinical and biochemical signs of CD, and for T1D characteristics. Results: The children's ages ranged from 11 months to 18 years. CD was confirmed in 32 out of 663 patients with T1D, with a prevalence of 4.8%. CD was excluded in 619 children and remained uncertain for 12 children, who had positive TGAs without the required criteria. We found that 95% of T1D children express HLA-DQ2 and/or -DQ8, which was 2.4 times higher than in the general population. Conclusions: An intestinal biopsy could be avoided to confirm CD in the majority of T1D children. Silent forms of CD are frequent and screening is recommended for all patients. Importantly, repeated TGA assessment is required in HLA genetically predisposed T1D patients, while it is unnecessary in the 5% who are HLA-DQ2 and -DQ8 negative.
Collapse
Affiliation(s)
- Chloé Girard
- Service de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, CHU de Toulouse, 31059 Toulouse, France
| | - Aurélie De Percin
- Service de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, CHU de Toulouse, 31059 Toulouse, France
| | - Carole Morin
- Service de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, CHU de Toulouse, 31059 Toulouse, France
| | - Maeva Talvard
- Service de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, CHU de Toulouse, 31059 Toulouse, France
| | | | - Nicolas Congy-Jolivet
- Department of Immunology, Rangueil Hospital, 31400 Toulouse, France
- Molecular Immunogenetics Laboratory, EA 3034, Faculty of Medicine Purpan, IFR150 (INSERM), 31400 Toulouse, France
| | - Claire Le Tallec
- Service de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, CHU de Toulouse, 31059 Toulouse, France
| | - Jean-Pierre Olives
- Service de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, CHU de Toulouse, 31059 Toulouse, France
- Faculté de Médecine, Université de Toulouse III, UPS, 31400 Toulouse, France
| | - Emmanuel Mas
- Service de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, CHU de Toulouse, 31059 Toulouse, France
- Institut de Recherche en Santé Digestive (IRSD), Université de Toulouse, INSERM, INRAE, ENVT, UPS, 31300 Toulouse, France
| |
Collapse
|
|
19
|
Kawasaki E. Anti-Islet Autoantibodies in Type 1 Diabetes. Int J Mol Sci 2023; 24:10012. [PMID: 37373160 PMCID: PMC10298549 DOI: 10.3390/ijms241210012] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 06/08/2023] [Accepted: 06/09/2023] [Indexed: 06/29/2023] Open
Abstract
Anti-islet autoantibodies serve as key markers in immune-mediated type 1 diabetes (T1D) and slowly progressive T1D (SPIDDM), also known as latent autoimmune diabetes in adults (LADA). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), tyrosine phosphatase-like protein IA-2 (IA-2A), and zinc transporter 8 (ZnT8A) are currently employed in the diagnosis, pathological analysis, and prediction of T1D. GADA can also be detected in non-diabetic patients with autoimmune diseases other than T1D and may not necessarily reflect insulitis. Conversely, IA-2A and ZnT8A serve as surrogate markers of pancreatic β-cell destruction. A combinatorial analysis of these four anti-islet autoantibodies demonstrated that 93-96% of acute-onset T1D and SPIDDM cases were diagnosed as immune-mediated T1D, while the majority of fulminant T1D cases were autoantibody-negative. Evaluating the epitopes and immunoglobulin subclasses of anti-islet autoantibodies help distinguish between diabetes-associated and non-diabetes-associated autoantibodies and is valuable for predicting future insulin deficiency in SPIDDM (LADA) patients. Additionally, GADA in T1D patients with autoimmune thyroid disease reveals the polyclonal expansion of autoantibody epitopes and immunoglobulin subclasses. Recent advancements in anti-islet autoantibody assays include nonradioactive fluid-phase assays and the simultaneous determination of multiple biochemically defined autoantibodies. Developing a high-throughput assay for detecting epitope-specific or immunoglobulin isotype-specific autoantibodies will facilitate a more accurate diagnosis and prediction of autoimmune disorders. The aim of this review is to summarize what is known about the clinical significance of anti-islet autoantibodies in the pathogenesis and diagnosis of T1D.
Collapse
Affiliation(s)
- Eiji Kawasaki
- Diabetes Center, Shin-Koga Hospital, Kurume 830-8577, Japan
| |
Collapse
|
|
20
|
Liu J, Zhang B, Zhu G, Liu C, Wang S, Zhao Z. Discovering genetic linkage between periodontitis and type 1 diabetes: A bioinformatics study. Front Genet 2023; 14:1147819. [PMID: 37051594 PMCID: PMC10083320 DOI: 10.3389/fgene.2023.1147819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 03/15/2023] [Indexed: 03/29/2023] Open
Abstract
Background: Relationship between periodontitis (PD) and type 1 diabetes (T1D) has been reported, but the detailed pathogenesis requires further elucidation. This study aimed to reveal the genetic linkage between PD and T1D through bioinformatics analysis, thereby providing novel insights into scientific research and clinical treatment of the two diseases.Methods: PD-related datasets (GSE10334, GSE16134, GSE23586) and T1D-related datasets(GSE162689)were downloaded from NCBI Gene Expression Omnibus (GEO). Following batch correction and merging of PD-related datasets as one cohort, differential expression analysis was performed (adjusted p-value <0.05 and ∣log2 fold change| > 0.5), and common differentially expressed genes (DEGs) between PD and T1D were extracted. Functional enrichment analysis was conducted via Metascape website. The protein-protein interaction (PPI) network of common DEGs was generated in The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Hub genes were selected by Cytoscape software and validated by receiver operating characteristic (ROC) curve analysis.Results: 59 common DEGs of PD and T1D were identified. Among these DEGs, 23 genes were commonly upregulated, and 36 genes were commonly downregulated in both PD- and T1D-related cohorts. Functional enrichment analysis indicated that common DEGs were mainly enriched in tube morphogenesis, supramolecular fiber organization, 9 + 0 non-motile cilium, plasma membrane bounded cell projection assembly, glomerulus development, enzyme-linked receptor protein signaling pathway, endochondral bone morphogenesis, positive regulation of kinase activity, cell projection membrane and regulation of lipid metabolic process. After PPI construction and modules selection, 6 hub genes (CD34, EGR1, BBS7, FMOD, IGF2, TXN) were screened out and expected to be critical in linking PD and T1D. ROC analysis showed that the AUC values of hub genes were all greater than 70% in PD-related cohort and greater than 60% in T1D-related datasets.Conclusion: Shared molecular mechanisms between PD and T1D were revealed in this study, and 6 hub genes were identified as potential targets in treating PD and T1D.
Collapse
Affiliation(s)
- Junqi Liu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Bo Zhang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Guanyin Zhu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Chenlu Liu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Shuangcheng Wang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zhihe Zhao
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- *Correspondence: Zhihe Zhao,
| |
Collapse
|
|
21
|
Popoviciu MS, Kaka N, Sethi Y, Patel N, Chopra H, Cavalu S. Type 1 Diabetes Mellitus and Autoimmune Diseases: A Critical Review of the Association and the Application of Personalized Medicine. J Pers Med 2023; 13:jpm13030422. [PMID: 36983604 PMCID: PMC10056161 DOI: 10.3390/jpm13030422] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 02/17/2023] [Accepted: 02/24/2023] [Indexed: 03/02/2023] Open
Abstract
Type 1 Diabetes Mellitus (T1DM) is a common hyperglycemic disease characterized by the autoimmune destruction of insulin-producing beta cells of the pancreas. Various attempts have been made to understand the complex interplay of genetic and environmental factors which lead to the development of the autoimmune response in an individual. T1DM is frequently associated with other autoimmune illnesses, the most common being autoimmune thyroid disorders affecting more than 90% of people with T1D and autoimmune disorders. Antithyroid antibodies are present in around 20% of children with T1D at the start of the illness and are more frequent in girls. Patients with T1DM often have various other co-existing multi-system autoimmune disorders including but not limited to thyroid diseases, parathyroid diseases, celiac disease, vitiligo, gastritis, skin diseases, and rheumatic diseases. It is a consistent observation in clinics that T1DM patients have other autoimmune disorders which in turn affect their prognosis. Concomitant autoimmune illness might affect diabetes care and manifest itself clinically in a variety of ways. A thorough understanding of the complex pathogenesis of this modern-day epidemic and its association with other autoimmune disorders has been attempted in this review in order to delineate the measures to prevent the development of these conditions and limit the morbidity of the afflicted individuals as well. The measures including antibody screening in susceptible individuals, early identification and management of other autoimmune disorders, and adoption of personalized medicine can significantly enhance the quality of life of these patients. Personalized medicine has recently gained favor in the scientific, medical, and public domains, and is frequently heralded as the future paradigm of healthcare delivery. With the evolution of the ‘omics’, the individualization of therapy is not only closer to reality but also the need of the hour.
Collapse
Affiliation(s)
| | - Nirja Kaka
- PearResearch, Dehradun 248001, India
- Department of Medicine, GMERS Medical College, Himmatnagar 383001, India
| | - Yashendra Sethi
- PearResearch, Dehradun 248001, India
- Department of Medicine, Government Doon Medical College, HNB Uttarakhand Medical Education University, Dehradun 248001, India
| | - Neil Patel
- PearResearch, Dehradun 248001, India
- Department of Medicine, GMERS Medical College, Himmatnagar 383001, India
| | - Hitesh Chopra
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India
| | - Simona Cavalu
- Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania
- Correspondence:
| |
Collapse
|
|
22
|
Chen Y, Wang Q, Xie Z, Huang G, Fan L, Li X, Zhou Z. The impact of family history of type 2 diabetes on clinical heterogeneity in idiopathic type 1 diabetes. Diabetes Obes Metab 2023; 25:417-425. [PMID: 36200314 DOI: 10.1111/dom.14884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/28/2022] [Accepted: 10/03/2022] [Indexed: 02/02/2023]
Abstract
AIM To investigate the impact of family history of type 2 diabetes (T2D) on the clinical phenotypes of patients with idiopathic type 1 diabetes (T1D). METHODS In clinically diagnosed T1D cases, a total of 335 idopathic T1D patients were included in the study, after excluding autoimmune T1D using islet autoantibody testing and monogenic diabetes using a custom monogenic diabetes gene panel obtained from clinically diagnosed T1D cases. A semi-structured questionnaire was used to collect information on the presence of T2D in first-degree relatives. The demographic and metabolic markers of idiopathic T1D patients were analysed. Subgroup analysis was performed to investigate potential interactions between T2D family history and human leukocyte antigen (HLA) genotypes. RESULTS A total of 18.2% of individuals with idiopathic T1D had a T2D family history, and these individuals were more likely to have features associated with T2D, such as older age of onset, higher body mass index at diagnosis, lower insulin dosage and better beta-cell function, as indicated by higher levels of fasting C-peptide and 2-hour postprandial C-peptide (all P < 0.05). Additionally, regardless of HLA susceptible genotypes, the impact of family history of T2D was consistently observed in idiopathic T1D patients. Multivariable analyses showed that T2D family history was negatively correlated with the risk of beta-cell function failure in idiopathic T1D patients (P < 0.05). CONCLUSIONS Family history of T2D may be implicated in the heterogeneity of idiopathic T1D patients.
Collapse
Affiliation(s)
- Yan Chen
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Qianrong Wang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Zhiguo Xie
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Gan Huang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Li Fan
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Xia Li
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Zhiguang Zhou
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| |
Collapse
|
|
23
|
Chang X, Wang Z, Guo H, Xu Y, Ogihara A. Effect of Physical Activity/Exercise on Cardiorespiratory Fitness in Children and Adolescents with Type 1 Diabetes: A Scoping Review. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:1407. [PMID: 36674162 PMCID: PMC9860959 DOI: 10.3390/ijerph20021407] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/25/2022] [Accepted: 01/10/2023] [Indexed: 05/26/2023]
Abstract
The most common type of diabetes among children and adolescents is type 1 diabetes mellitus (T1DM), which is associated with an increased risk of cardiovascular disease (CVD). Additionally, lower levels of cardiorespiratory fitness (CRF) are linked to an increased risk of CVD. Regular exercise is associated with a decreased risk of CVD and improved CRF. We conducted this scoping review to assess the effects of exercise on CRF in youth with T1DM. Three electronic databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) were used to search for the relevant literature. In this analysis, the PICOS method was used to select studies and was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines scoping review guidelines for the evaluation of the effects of physical activity and cardiac function; the criteria may include the type and intensity of physical activity, the duration of the intervention, peak oxygen consumption (VO2), peak minute ventilation (VE), and peak heart rate of cardiorespiratory fitness. Screening resulted in 434 records. Of these, nine articles were included in our study. These nine studies were experimental (noncontrolled trials or randomized controlled trials) (n = 7) and observational (cross-sectional) (n = 2), and could be used to evaluate the effectiveness of physical activity interventions on cardiac function. The effects of exercise on CRF in youth with T1DM vary according to the type, frequency, and intensity of the exercise. According to our review, the duration of exercise included in the studies did not meet the recommendations of the guidelines for youth with T1DM. Additionally, half of the studies revealed that exercise could optimize the lipid profile in youth with T1DM. Hence, this research is to provide an overview of the effects of physical activity and exercise on CRF, cardiovascular fitness, lipid profile, and blood pressure in youth with T1DM, as well as identified potential limitations of the existing studies. Nevertheless, the limited number of clinical studies employing exercise interventions for children and adolescents with T1DM emphasize the need for more studies in this area, and more specific modes of exercise should be developed in the future.
Collapse
Affiliation(s)
- Xinyi Chang
- Graduate School of Human Sciences, Waseda University, Tokorozawa 359-1192, Japan
| | - Ziheng Wang
- Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8579, Japan
| | - Hongzhi Guo
- Graduate School of Human Sciences, Waseda University, Tokorozawa 359-1192, Japan
| | - Yinghan Xu
- Graduate School of Human Sciences, Waseda University, Tokorozawa 359-1192, Japan
| | - Atsushi Ogihara
- Faculty of Human Sciences, Waseda University, Tokorozawa 359-1192, Japan
| |
Collapse
|
|
24
|
Fröhlich-Reiterer E, Elbarbary NS, Simmons K, Buckingham B, Humayun KN, Johannsen J, Holl RW, Betz S, Mahmud FH. ISPAD Clinical Practice Consensus Guidelines 2022: Other complications and associated conditions in children and adolescents with type 1 diabetes. Pediatr Diabetes 2022; 23:1451-1467. [PMID: 36537532 DOI: 10.1111/pedi.13445] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Affiliation(s)
- Elke Fröhlich-Reiterer
- Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
| | | | - Kimber Simmons
- Barbara Davis Center for Diabetes, University of Colorado, Denver, Colorado, USA
| | - Bruce Buckingham
- Division of Endocrinology and Diabetes, Department of Pediatrics, Stanford University Medical Center, Stanford, California, USA
| | - Khadija N Humayun
- Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan
| | - Jesper Johannsen
- Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Herlev and Steno Diabetes Center Copenhagen, Copenhagen, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Reinhard W Holl
- Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, Ulm, Germany
| | - Shana Betz
- Parent/Advocate for people with diabetes, Markham, Canada
| | - Farid H Mahmud
- Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| |
Collapse
|
|
25
|
Chranioti I, Vartzelis G, Maritsi D, Tsolia M. A Co-diagnosis of Crohn Disease and Autoimmune Diabetes in an Adolescent Patient. JPGN REPORTS 2022; 3:e265. [PMID: 37168469 PMCID: PMC10158271 DOI: 10.1097/pg9.0000000000000265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 09/01/2022] [Indexed: 05/13/2023]
Abstract
Inflammatory bowel disease (IBD) is a lifelong, immune-mediated disorder that often occurs in childhood and is becoming increasingly common worldwide. Diagnosis of IBD in children remains difficult due to the spectrum of symptoms, including gastrointestinal and extraintestinal manifestations. Type 1 diabetes mellitus (T1D) is one of the most common autoimmune diseases in children and adolescents. Classic manifestations of T1D in young people include polyuria, polydipsia, abdominal pain, weight loss, and ketoacidosis. However, children with autoimmunity of pancreatic β-cells may remain euglycemic and asymptomatic for many years. An accurate and prompt diagnosis of IBD and T1D is particularly important in children because they can negatively affect growth, psychosocial function and overall well-being. We present a case in which a previously healthy child was co-diagnosed with Crohn disease and T1D during a routine pediatric evaluation in the outpatient clinic of a peripheral secondary hospital.
Collapse
Affiliation(s)
- Ioanna Chranioti
- From the Pediatric Department, General Hospital of Ierapetra, Crete, Greece
- Second Pediatric Department, National and Kapodistrian University of Athens, Medical School, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece
| | - George Vartzelis
- Second Pediatric Department, National and Kapodistrian University of Athens, Medical School, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece
| | - Despoina Maritsi
- Second Pediatric Department, National and Kapodistrian University of Athens, Medical School, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece
| | - Maria Tsolia
- Second Pediatric Department, National and Kapodistrian University of Athens, Medical School, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece
| |
Collapse
|
|
26
|
Kakleas K, Kossyva L, Korona A, Kafassi N, Karanasios S, Karavanaki K. Predictors of associated and multiple autoimmunity in children and adolescents with type 1 diabetes mellitus. Ann Pediatr Endocrinol Metab 2022; 27:192-200. [PMID: 34793669 PMCID: PMC9537678 DOI: 10.6065/apem.2142168.084] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 11/01/2021] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Type 1 diabetes mellitus (T1DM) is an autoimmune condition characterised by the presence of antipancreatic antibodies. The autoimmune process is also directed against other organs, most frequently against the thyroid gland, intestinal mucosa, and gastric parietal cells. METHODS Our investigation included 121 children with T1DM with a mean age±standard deviation of 11.99±4.63 years (range, 2.0-20.0 years). We explored the frequency of associated autoimmunity; the presence of predictive factors such as current age, sex, and severity at diabetes diagnosis; T1DM duration; and family history of autoimmunity. RESULTS Associated autoimmunity was present in 28.9% of T1DM patients. Children with associated autoimmunity were older at diabetes diagnosis (p=0.009) and had a longer diabetes duration compared to children without associated autoimmunity (p=0.044). Adolescents aged 12-20 years had a statistically significant higher chance of developing thyroid autoimmunity compared to children aged 1-5 years (p=0.019). Multiple autoimmunity (MA), T1DM, and 2 or more autoimmune diseases were present in 5.8% of the study population. All children with MA presented with ketoacidosis at diabetes diagnosis and had a higher percentage of familial autoimmunity (p=0.042). The familial autoimmunity of these patients most frequently affected ≥3 relatives (p=0.026) and was more frequently diagnosed before 5 years of age (p=not significant). CONCLUSION Associated autoimmunity was present in almost one-third of T1DM patients. Significant associations with associated autoimmunity were longer diabetes duration, female sex, older age at diabetes diagnosis, and glutamic acid decarboxylase positivity. Predictors of MA were age <5 years at T1DM diagnosis, the presence of diabetic ketoacidosis at diagnosis, and a significant family history of autoimmunity.
Collapse
Affiliation(s)
- Konstantinos Kakleas
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, 'P. & A. Kyriakou' Children's Hospital, Athens, Greece,Address for correspondence: Konstantinos Kakleas Athens General Children's Hospital "Pan. & Aglaia Kyriakou", Thivon kai Levadias, Athens P.C. 11527 Telephone: 0030-213 2009000
| | - Lydia Kossyva
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, 'P. & A. Kyriakou' Children's Hospital, Athens, Greece
| | - Anastasia Korona
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, 'P. & A. Kyriakou' Children's Hospital, Athens, Greece
| | | | - Spyridon Karanasios
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, 'P. & A. Kyriakou' Children's Hospital, Athens, Greece
| | - Kyriaki Karavanaki
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, 'P. & A. Kyriakou' Children's Hospital, Athens, Greece
| |
Collapse
|
|
27
|
Burbaud M, Renard E, Jellimann S, Luc A, Di Patrizio M, Remen T, Legagneur C. Additional autoimmune diseases associated with type 1 diabetes in children and adolescents: A French single-center study from 2014 to 2021. Arch Pediatr 2022; 29:381-387. [DOI: 10.1016/j.arcped.2022.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 12/01/2021] [Accepted: 03/26/2022] [Indexed: 11/28/2022]
|
|
28
|
Modarelli R, Sarah S, Ramaker ME, Bolobiongo M, Benjamin R, Gumus Balikcioglu P. Pediatric Diabetes on the Rise: Trends in Incident Diabetes During the COVID-19 Pandemic. J Endocr Soc 2022; 6:bvac024. [PMID: 35265783 PMCID: PMC8900286 DOI: 10.1210/jendso/bvac024] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Indexed: 11/19/2022] Open
Abstract
Context The effects of the coronavirus disease 2019 (COVID-19) pandemic on the incident cases of pediatric type 1 diabetes (T1D) and type 2 diabetes (T2D) are not clear. Objective To identify trends in incidence and presentation of pediatric new-onset T1D and T2D during the COVID-19 pandemic. Methods A retrospective chart review was conducted. Demographics, anthropometrics, and initial laboratory results from patients ages 0 through 21 years who presented with new-onset diabetes to a pediatric tertiary care center were recorded. Results During the pandemic, incident cases of pediatric T1D increased from 31 in each of the prior 2 years to 46; an increase of 48%. Incident cases of pediatric T2D increased by 231% from 2019 to 2020. The number of incident cases of pediatric T2D increased significantly more than the number of incident cases of pediatric T1D (P = 0.009). Patients with T2D were more likely to present in diabetic ketoacidosis (DKA), though this was not statistically significant (P = 0.093). Severe DKA was higher compared with moderate DKA (P = 0.036) in incident cases of pediatric T2D. During the pandemic, for the first time, incident cases of T2D accounted for more than one-half of all newly diagnosed pediatric diabetes cases (53%). Conclusions There were more incident pediatric T1D and T2D cases as well as an increase in DKA severity in T2D at presentation during the COVID-19 pandemic. More importantly, incident T2D cases were higher than the incident T1D during the pandemic. This clearly suggests a disruption and change in the pediatric diabetes trends with profound individual and community health consequences.
Collapse
Affiliation(s)
- Rachel Modarelli
- Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
| | - Salma Sarah
- Division of Pediatric Endocrinology and Diabetes, Duke University Medical Center, Durham, NC 27705, USA
| | - Megan E Ramaker
- Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA
| | - Mboli Bolobiongo
- Duke School of Medicine, Master of Biomedical Sciences, Durham, NC 27710, USA
| | - Robert Benjamin
- Division of Pediatric Endocrinology and Diabetes, Duke University Medical Center, Durham, NC 27705, USA
| | - Pinar Gumus Balikcioglu
- Division of Pediatric Endocrinology and Diabetes, Duke University Medical Center, Durham, NC 27705, USA
- Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA
| |
Collapse
|
|
29
|
Wang Y, Yang Y, Liu Y, Guo A, Zhang Y. Cognitive impairments in type 1 diabetes mellitus model mice are associated with synaptic protein disorders. Neurosci Lett 2022; 777:136587. [PMID: 35337951 DOI: 10.1016/j.neulet.2022.136587] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 01/24/2022] [Accepted: 03/21/2022] [Indexed: 11/24/2022]
Abstract
An association between type 1 diabetes mellitus (T1DM) and cognitive impairment was recently reported. However, the mechanisms by which T1DM induces cognitive impairment are still unknown. Here, we confirmed that T1DM mice induced by streptozotocin (STZ) injection had impaired working memory and spatial memory. We observed long-term potentiation (LTP) induction defects and synaptic loss in mice 20 weeks after STZ injection. We also found decreased levels of synaptic proteins, including the N-methyl-D-aspartic acid receptor (NMDAR) subunit NR2A, synaptophysin (SYP), and postsynaptic density 95 (PSD95), in the hippocampus and prefrontal cortex, revealing similarities in the alteration patterns of these synaptic proteins in aged Alzheimer's disease (AD) APP/PS1 mice and T1DM mice. Taken together, these findings expand our understanding of the mechanisms underlying T1DM-induced cognitive impairment.
Collapse
Affiliation(s)
- Yiming Wang
- State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China
| | - Yueqi Yang
- State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China
| | - Yiqiong Liu
- State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China
| | - Angyang Guo
- Duke Kunshan University, Kunshan, Jiangsu 215316, China
| | - Yan Zhang
- State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
| |
Collapse
|
|
30
|
Zhang B, Zhong W, Yang B, Li Y, Duan S, Huang J, Mao Y. Gene expression profiling reveals candidate biomarkers and probable molecular mechanisms in chronic stress. Bioengineered 2022; 13:6048-6060. [PMID: 35184642 PMCID: PMC8973686 DOI: 10.1080/21655979.2022.2040872] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Chronic stress refers to nonspecific systemic reactions under the over-stimulation of different external and internal factors for a long time. Previous studies confirmed that chronic psychological stress had a negative effect on almost all tissues and organs. We intended to further identify potential gene targets related to the pathogenesis of chronic stress-induced consequences involved in different diseases. In our study, mice in the model group lived under the condition of chronic unpredictable mild stress (CUMS) until they expressed behaviors like depression which were supposed to undergo chronic stress. We applied high-throughput RNA sequencing to assess mRNA expression and obtained transcription profiles in lung tissue from CUMS mice and control mice for analysis. In view of the prediction of high-throughput RNA sequences and bioinformatics software, and mRNA regulatory network was constructed. First, we conducted differentially expressed genes (DEGs) and obtained 282 DEGs between CUMS (group A) and the control model (group B). Then, we conducted functional and pathway enrichment analyses. In general, the function of upregulated regulated DEGs is related to immune and inflammatory responses. PPI network identified several essential genes, of which ten hub genes were related to the T cell receptor signaling pathway. qRT-PCR results verified the regulatory network of mRNA. The expressions of CD28, CD3e, and CD247 increased in mice with CUMS compared with that in control. This illustrated immune pathways are related to the pathological molecular mechanism of chronic stress and may provide information for identifying potential biomarkers and early detection of chronic stress.
Collapse
Affiliation(s)
- Bohan Zhang
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, SH, China
| | - Weijie Zhong
- Department of Neurosurgery, Ninth People Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, SH, China
| | - Biao Yang
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, SH, China
| | - Yi Li
- Department of Neurosurgery, Ninth People Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, SH, China
| | - Shuxian Duan
- Department of Neurosurgery, Ninth People Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, SH, China
| | - Junlong Huang
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, SH, China
| | - Yanfei Mao
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, SH, China
| |
Collapse
|
|
31
|
Wardinger J, Sussman L, Irish E, Foulke L, Litwa B, Kaslovsky R. Autoimmune overload: An atypical presentation of granulomatosis with polyangiitis in an adolescent with type 1 diabetes mellitus. Pediatr Pulmonol 2022; 57:322-324. [PMID: 34695301 DOI: 10.1002/ppul.25724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 09/11/2021] [Accepted: 09/29/2021] [Indexed: 11/12/2022]
Affiliation(s)
- Jamie Wardinger
- Department of Pediatrics, Albany Medical Center, Albany, New York, USA.,Department of Neonatal-Perinatal Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Lauren Sussman
- Department of Pediatrics, Albany Medical Center, Albany, New York, USA
| | - Elizabeth Irish
- Shaffer Library of Health Sciences, Albany Medical College, Albany, New York, USA
| | - Llewellyn Foulke
- Department of Pathology, Albany Medical Center, Albany, New York, USA
| | | | - Robert Kaslovsky
- Department of Pediatrics (Pulmonary), Albany Medical College, Albany, New York, USA
| |
Collapse
|
|
32
|
Li X, Shi S, Jing D, Li X, Zhang B, Bie Q. Signal transduction mechanism of exosomes in diabetic complications (Review). Exp Ther Med 2021; 23:155. [PMID: 35069836 DOI: 10.3892/etm.2021.11078] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 11/24/2021] [Indexed: 11/05/2022] Open
Affiliation(s)
- Xueting Li
- Department of Clinical Medicine, Jining Medical University, Jining, Shandong 272000, P.R. China
| | - Shuo Shi
- Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China
| | - Dehuai Jing
- Department of Digestive Endoscopy and 4Nephrology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China
| | - Xinjian Li
- Department of Nephrology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272000, P.R. China
| | - Bin Zhang
- Department of Clinical Medicine, Jining Medical University, Jining, Shandong 272000, P.R. China
| | - Qingli Bie
- Department of Clinical Medicine, Jining Medical University, Jining, Shandong 272000, P.R. China
| |
Collapse
|
|
33
|
Zhou N, Liu W, Zhang W, Liu Y, Li X, Wang Y, Zheng R, Zhang Y. Wip1 regulates the immunomodulatory effects of murine mesenchymal stem cells in type 1 diabetes mellitus via targeting IFN-α/BST2. Cell Death Discov 2021; 7:326. [PMID: 34716317 PMCID: PMC8556269 DOI: 10.1038/s41420-021-00728-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 10/12/2021] [Accepted: 10/15/2021] [Indexed: 12/30/2022] Open
Abstract
Mesenchymal stem cells (MSCs) show significant therapeutic effects in type 1 diabetes mellitus (T1DM) as regulating the inflammatory processes. However, little is known about the detailed process of MSCs immunosuppression in T1DM. In this study, we investigated the effects of wild-type p53-induce phosphatase 1 (Wip1) on regulating MSCs immunosuppressive capacities in T1DM mice. We found that Wip1 knockout (Wip1-/-) MSCs had lower therapeutic effects in T1DM mice, and displayed weaker immunosuppressive capability. In vivo distribution analysis results indicated thatWip1-/-MSCs could home to the damaged pancreas and increase the expression of tumor necrosis factor-α (TNF-α), interleukin-17a (IL-17a), interferon-α(IFN-α), IFN-β, and IFN-γ, while decrease the expression of IL-4 and IL-10. Moreover, we confirmedWip1-/-MSCs exhibited weaker immunosuppressive capacity, as evidenced by enhanced expression of bone marrow stromal cell antigen 2(BST2) and IFN-α. In conclusion, these results revealed Wip1 affects MSCs immunomodulation by regulating the expression of IFN-α/BST2. Our study uncovered that Wip1 is required to regulate the therapeutic effects of MSCs on T1DM treatment, indicating a novel role of Wip1 in MSCs immunoregulation properties.
Collapse
Affiliation(s)
- Na Zhou
- Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, 100850, China
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Weijiang Liu
- Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, 100850, China
| | - Wei Zhang
- Department of Medical Administration, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China
| | - Yuanlin Liu
- Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, 100850, China
| | - Xue Li
- Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, 100850, China
| | - Yang Wang
- Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, 100850, China
| | - Rongxiu Zheng
- Department of Pediatrics, Tianjin Medical University General Hospital, Tianjin, 300052, China.
| | - Yi Zhang
- Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
| |
Collapse
|
|
34
|
Márquez A, Martín J. Genetic overlap between type 1 diabetes and other autoimmune diseases. Semin Immunopathol 2021; 44:81-97. [PMID: 34595540 DOI: 10.1007/s00281-021-00885-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Accepted: 08/12/2021] [Indexed: 12/11/2022]
Abstract
Type 1 diabetes (T1D) is a chronic disease caused by the destruction of pancreatic β cells, which is driven by autoreactive T lymphocytes. It has been described that a high proportion of T1D patients develop other autoimmune diseases (AIDs), such as autoimmune thyroid disease, celiac disease, or vitiligo, which suggests the existence of common etiological factors among these disorders. In this regard, genetic studies have identified a high number of loci consistently associated with T1D that also represent established genetic risk factors for other AIDs. In addition, studies focused on identifying the shared genetic component in autoimmunity have described several common susceptibility loci with a potential role in T1D. Elucidation of this genetic overlap has been useful in identifying key molecular pathways with a pathogenic role in multiple disorders. In this review, we summarize recent advances in understanding the shared genetic component between T1D and other AIDs and discuss how the identification of common pathogenic mechanisms can help in the development of new therapeutic approaches as well as in improving the use of existing drugs.
Collapse
Affiliation(s)
- Ana Márquez
- Institute of Parasitology and Biomedicine López-Neyra. Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), Granada, Spain.,Systemic Autoimmune Disease Unit, Hospital Clínico San Cecilio, Instituto de Investigación Biosanitaria Ibs. GRANADA, Granada, Spain
| | - Javier Martín
- Institute of Parasitology and Biomedicine López-Neyra. Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), Granada, Spain.
| |
Collapse
|
|
35
|
Agrawal A, Narayan G, Gogoi R, Thummer RP. Recent Advances in the Generation of β-Cells from Induced Pluripotent Stem Cells as a Potential Cure for Diabetes Mellitus. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1347:1-27. [PMID: 34426962 DOI: 10.1007/5584_2021_653] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Diabetes mellitus (DM) is a group of metabolic disorders characterized by high blood glucose levels due to insufficient insulin secretion, insulin action, or both. The present-day solution to diabetes mellitus includes regular administration of insulin, which brings about many medical complications in diabetic patients. Although islet transplantation from cadaveric subjects was proposed to be a permanent cure, the increased risk of infections, the need for immunosuppressive drugs, and their unavailability had restricted its use. To overcome this, the generation of renewable and transplantable β-cells derived from autologous induced pluripotent stem cells (iPSCs) has gained enormous interest as a potential therapeutic strategy to treat diabetes mellitus permanently. To date, extensive research has been undertaken to derive transplantable insulin-producing β-cells (iβ-cells) from iPSCs in vitro by recapitulating the in vivo developmental process of the pancreas. This in vivo developmental process relies on transcription factors, signaling molecules, growth factors, and culture microenvironment. This review highlights the various factors facilitating the generation of mature β-cells from iPSCs. Moreover, this review also describes the generation of pancreatic progenitors and β-cells from diabetic patient-specific iPSCs, exploring the potential of the diabetes disease model and drug discovery. In addition, the applications of genome editing strategies have also been discussed to achieve patient-specific diabetes cell therapy. Last, we have discussed the current challenges and prospects of iPSC-derived β-cells to improve the relative efficacy of the available treatment of diabetes mellitus.
Collapse
Affiliation(s)
- Akriti Agrawal
- Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India
| | - Gloria Narayan
- Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India
| | - Ranadeep Gogoi
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research Guwahati, Changsari, Guwahati, Assam, India
| | - Rajkumar P Thummer
- Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India.
| |
Collapse
|
|
36
|
Type 1 Diabetes and Addison’s Disease: When the Diagnosis Is Suggested by the Continuous Glucose Monitoring System. CHILDREN 2021; 8:children8080702. [PMID: 34438593 PMCID: PMC8391923 DOI: 10.3390/children8080702] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 07/20/2021] [Accepted: 08/06/2021] [Indexed: 01/14/2023]
Abstract
Our objective is to emphasize the important role of continuous glucose monitoring (CGM) in suggesting adrenal insufficiency in patients affected by type 1 diabetes. We describe an adolescent girl with type 1 diabetes and subsequent latent Addison’s disease diagnosed based on a recurrent hypoglycemic trend detected by CGM. In patients with type 1 diabetes, persistent unexplained hypoglycemic episodes at dawn together with reduced insulin requirement arouse souspicionof adrenal insufficiency. Adrenal insufficiency secondary to autoimmune Addison’s disease, even if rarely encountered among young patients, may be initially symptomless and characterized by slow progression up to acute adrenal crisis, which represents a potentially life-threatening condition. Besides glycometabolic assessment and adequate insulin dosage adjustment, type 1 diabetes needs prompt recognition of potentially associated autoimmune conditions. Among these, Addison’s disease can be suspected, although latent or paucisymptomatic, through periodic and careful evaluation of CGM data.
Collapse
|
|
37
|
Gougourelas D, Tsentidis C, Koufadaki AM, Koutsovasilis A, Gougourela E, Karanasios S, Sotiropoulos A, Bousboulas S, Karavanaki KA. Associated autoimmunity in Type 1 Diabetes and latent autoimmune diabetes of adults: The role of glutamic-acid decarboxylase autoantibodies. Diabetes Res Clin Pract 2021; 175:108847. [PMID: 33945840 DOI: 10.1016/j.diabres.2021.108847] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 04/19/2021] [Accepted: 04/28/2021] [Indexed: 11/17/2022]
Abstract
AIMS To determine the prevalence of Associated Autoimmune Diseases (AADs) in Latent Autoimmune Diabetes of Adults (LADA) versus autoimmune Type 1 Diabetes (T1D) and the role of glutamic-acid decarboxylase antibodies (GADA) and other factors. METHODS Adults with autoimmune diabetes mellitus (DM) were recruited from the Diabetes Center of Nikaia-Piraeus Hospital. Demographic and clinical parameters were recorded and anti-pancreatic and organ-specific antibodies were measured. RESULTS Of 160 patients, 33.75% had one AAD and 24.37% had two or more. Patients with LADA had higher overall prevalence of AADs, mainly autoimmune thyroiditis and gastritis. Celiac disease was present only in T1D. GADA positive patients had higher prevalence of AADs and multiple autoimmunity, especially thyroiditis and gastritis. Patients with LADA had higher rates of positive GADA or islet-cell antibodies (ICA). After controlling for LADA, GADA remained a significant predictor of AADs. Female gender and chronological age were also significant predictors of AADs. CONCLUSIONS AADs were present in 58.13% of patients. Patients with LADA were more prone to a generalized autoimmune disorder than those with T1D. AADs development was significantly associated with female sex, older age and positive GADA, which proved an independent marker of associated autoimmunity.
Collapse
Affiliation(s)
- Dimitrios Gougourelas
- Diabetes Center, General Hospital of Nikaia - Piraeus "Agios Panteleimon", Athens, Greece.
| | - Charalampos Tsentidis
- Department of Endocrinology, Metabolism & Diabetes Mellitus, General Hospital of Nikaia - Piraeus "Agios Panteleimon", Athens, Greece
| | - Athina Maria Koufadaki
- Diabetes and Metabolism Clinic, 2(nd) Department of Pediatrics, National and Kapodistrian University of Athens, "P&A Kyriakou" Children's Hospital, Athens, Greece
| | | | - Eupraxia Gougourela
- Diabetes Center, General Hospital of Nikaia - Piraeus "Agios Panteleimon", Athens, Greece
| | - Spyridon Karanasios
- Diabetes and Metabolism Clinic, 2(nd) Department of Pediatrics, National and Kapodistrian University of Athens, "P&A Kyriakou" Children's Hospital, Athens, Greece
| | - Alexios Sotiropoulos
- Diabetes Center, General Hospital of Nikaia - Piraeus "Agios Panteleimon", Athens, Greece
| | - Stavros Bousboulas
- Diabetes Center, General Hospital of Nikaia - Piraeus "Agios Panteleimon", Athens, Greece
| | - Kyriaki Athina Karavanaki
- Diabetes and Metabolism Clinic, 2(nd) Department of Pediatrics, National and Kapodistrian University of Athens, "P&A Kyriakou" Children's Hospital, Athens, Greece
| |
Collapse
|
|
38
|
Large-Scale Screening in General Population Children for Celiac Disease with a Multiplex Electrochemiluminescence (ECL) Assay. J Immunol Res 2021; 2020:8897656. [PMID: 33426098 PMCID: PMC7775136 DOI: 10.1155/2020/8897656] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 12/15/2020] [Accepted: 12/17/2020] [Indexed: 11/17/2022] Open
Abstract
Background Autoimmunity Screening for Kids (ASK) study was launched to screen general population children for type 1 diabetes (T1D) and celiac disease (CD). Methods A total of 23,319 children from general population were screened. A high throughput multiplex electrochemiluminescence (ECL) assay to screen multiautoantibodies in a single well was applied, parallel with a standard radiobinding assay (RBA). All children with any positive autoantibodies in screening were revisited within one month for confirmation and followed every 6 months. Results Among 23,319 children, 2.6% (606/23,319) of children were tested positive for TGA. Multiplex ECL assay detected more TGA (584/23,319) in the initial screening than RBA (490/23,319, p = 0.004) and was able to detect TGA earlier than RBA in a subset of children by 0.8 to 34.8 months. Prevalence of TGA by either ECL or RBA in children with islet autoantibodies was found significantly higher than overall prevalence in general population screened. Conclusions A multiplex ECL assay was more sensitive than standard RBA by identifying more TGA positivity and detecting TGA earlier in general population screening. It also provides a high efficient tool with its unique advantage of multiplexing measurements to screen for multiple autoimmune diseases simultaneously in general population.
Collapse
|
|
39
|
Derrou S, El Guendouz F, Benabdelfedil Y, Chakri I, Ouleghzal H, Safi S. The profile of autoimmunity in Type 1 diabetes patients. Ann Afr Med 2021; 20:19-23. [PMID: 33727507 PMCID: PMC8102891 DOI: 10.4103/aam.aam_8_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 04/12/2020] [Accepted: 05/06/2020] [Indexed: 01/01/2023] Open
Abstract
Background Type 1 diabetes mellitus (T1DM) is an autoimmune disorder caused by pancreatic β-cells destruction. Anti-pancreatic antibodies are the witness of β-cell destruction and their dosage is mainly used for etiological diagnosis. Patients with T1DM are at increased risk of developing other autoimmune reactions, which may involve other organs, resulting in organ specific autoimmune disease. The most frequently encountered are autoimmune thyroid disease, followed by celiac and gastric disease and other rare autoimmune diseases. Objectives The purpose of this study is to investigate the prevalence of autoimmune markers in patients with T1DM. Methods The study was conducted at the Department of Endocrinology of the Military Hospital Moulay Ismail in Meknes Morocco, from January 2016 to December 2018. All Type 1 diabetes patients consulting during the study period were included in the study. Their clinical and biochemical data were collected at their first presentation, made up of anti-pancreatic antibodies (glutamic acid decarboxylase [GAD] antibody, tyrosine phosphatase antibody, and islet cell antibody) and other organ-specific antibodies: the thyroid (antithyroid peroxidase antibody, antithyroglobulin antibody, and antithyroid-stimulating hormone receptor antibody), the intestine (IgA antitissue transglutaminase antibody), the adrenal gland (anti-21 hydroxylase antibody), and the stomach (antigastric parietal cell antibody and anti-intrinsic factor antibody). Results Fifty-four patients were included, with an average age of 26 years. GAD, tyrosine phosphatase, and islet cell antibodies were detected in 74%, 22%, and 3.7%, respectively, of the 54 patients examined. The prevalence of extrapancreatic autoimmunity was 45% with a large preponderance among different immunities of those from thyroid and celiac diseases (CDs). Conclusion Our results confirm that patients with Type 1 diabetes should be investigated for the presence of autoimmune diseases mainly from thyroid and CDs.
Collapse
Affiliation(s)
- Sara Derrou
- Department of Endocrinology, Diabetology and Nutrition, Military Hospital Moulay Ismail, Meknes, Morocco
- Faculty of Medicine and Pharmacy, University Sidi Mohamed Ben Abdellah, Fez, Morocco
| | - Fayçal El Guendouz
- Department of Endocrinology, Diabetology and Nutrition, Military Hospital Moulay Ismail, Meknes, Morocco
- Faculty of Medicine and Pharmacy, University Sidi Mohamed Ben Abdellah, Fez, Morocco
| | - Yousra Benabdelfedil
- Department of Endocrinology, Diabetology and Nutrition, Military Hospital Moulay Ismail, Meknes, Morocco
- Faculty of Medicine and Pharmacy, University Sidi Mohamed Ben Abdellah, Fez, Morocco
| | - Imad Chakri
- Department of Clinical Research and Community Health Laboratory, Faculty of Medicine and Pharmacy, University Sidi Mohamed Ben Abdellah, Fez, Morocco
| | - Hassan Ouleghzal
- Department of Endocrinology, Diabetology and Nutrition, Military Hospital Moulay Ismail, Meknes, Morocco
- Faculty of Medicine and Pharmacy, University Sidi Mohamed Ben Abdellah, Fez, Morocco
| | - Somaya Safi
- Department of Endocrinology, Diabetology and Nutrition, Military Hospital Moulay Ismail, Meknes, Morocco
- Faculty of Medicine and Pharmacy, University Sidi Mohamed Ben Abdellah, Fez, Morocco
| |
Collapse
|
|
40
|
Abdul-Rahman A. Multiple autoimmune syndrome complicating the management of diabetic retinopathy. Am J Ophthalmol Case Rep 2020; 20:100928. [PMID: 33073055 PMCID: PMC7548932 DOI: 10.1016/j.ajoc.2020.100928] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 09/03/2020] [Accepted: 09/13/2020] [Indexed: 11/16/2022] Open
Abstract
Purpose Observations Conclusion and Importance
Collapse
|
|
41
|
Chakarova N, Dimova R, Serdarova M, Grozeva G, Kuncheva M, Kamenov L, Tankova T. Islet, thyroid and transglutaminase antibodies in adult Bulgarian patients with type 1 diabetes. Endocrine 2020; 70:299-306. [PMID: 32594378 DOI: 10.1007/s12020-020-02395-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 06/18/2020] [Indexed: 01/02/2023]
Abstract
AIM The aim of the study was to assess the prevalence and relationship of islet antibodies and autoantibodies of the most common associated autoimmune diseases-autoimmune thyroid disease (AITD) and celiac disease, in adult Bulgarian patients with type 1 diabetes of short duration. MATERIAL AND METHODS 160 type 1 diabetes patients, of mean age 36.3 ± 10.9 years, mean BMI 23.0 ± 4.2 kg/m2 and mean disease duration 1.35 ± 1.69 years were enrolled. Pancreatic islet cell antibodies-glutamic acid decarboxylase antibodies (GAD 65-Ab), tyrosine phosphatase antibodies (IA 2-Ab), and zinc transporter 8 antibodies (ZnT8-Ab), thyroid antibodies-thyroperoxidase and thyroglobulin antibodies, and transglutaminase antibodies (TTG-IgA-Ab) were assessed by ELISA. RESULTS 87.5% of the patients had one or more of the islet antibodies-78.1% had GAD 65-Ab, 53.1%-ZnT8-Ab, and 34.4%-IA 2-Ab. 5% presented as just ZnT8-Ab positive. GAD 65-Ab identified 90.6% of the antibody positive patients. The addition of IA 2-Ab as a second immunologic marker identified 94.4%, while the use of ZnT8-Ab in second place identified 98.8% of the cases. 24.4% presented with positive thyroid antibodies and 33.8% had AITD. No relation was found between any of the islet antibodies and AITD. None of the patients was TTG-IgA-Ab positive. No significant correlations were established between the antibodies with different organ specificity. CONCLUSIONS In adult Bulgarian type 1 diabetes patients ZnT8-Ab is an independent diagnostic marker rating second in prevalence and diagnostic significance after GAD 65-Ab. AITD affects about one third of this population and routine screening is required, while screening for celiac disease is not justified.
Collapse
Affiliation(s)
- Nevena Chakarova
- Department of Endocrinology, Division of Diabetology, Medical University Sofia, Sofia, Bulgaria.
| | - Rumyana Dimova
- Department of Endocrinology, Division of Diabetology, Medical University Sofia, Sofia, Bulgaria
| | - Mina Serdarova
- Department of Endocrinology, Division of Diabetology, Medical University Sofia, Sofia, Bulgaria
| | - Greta Grozeva
- Department of Endocrinology, Division of Diabetology, Medical University Sofia, Sofia, Bulgaria
| | | | | | - Tsvetalina Tankova
- Department of Endocrinology, Division of Diabetology, Medical University Sofia, Sofia, Bulgaria
| |
Collapse
|
|
42
|
Cardinez N, Lovblom LE, Orszag A, Cherney DZI, Perkins BA. The Prevalence of Autoimmune Diseases in Longstanding Diabetes: Results from the Canadian Study of Longevity in Adults with Type 1 Diabetes. Can J Diabetes 2020; 45:512-518.e1. [PMID: 33358269 DOI: 10.1016/j.jcjd.2020.10.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 10/21/2020] [Accepted: 10/23/2020] [Indexed: 11/24/2022]
Abstract
OBJECTIVE We aimed to determine the prevalence of autoimmune diseases (e.g. thyroid disease, celiac disease, etc) in Canadians with longstanding type 1 diabetes (T1D) and to explore sex-specific differences and the association with complications. METHODS Cross-sectional data were analyzed in an exploratory secondary analysis from the Canadian Study of Longevity in Type 1 Diabetes, a nationwide registry of people with T1D of at least 50 years' duration. In total, 374 participants provided self-reported questionnaire data and physician-reported laboratory results. Student's t-test, the Wilcoxon rank-sum test, the χ2 test and logistic regression were used to identify associations with autoimmune diseases. RESULTS The 374 participants had a median T1D duration of 53 years (interquartile range, 51 to 58) and a median age of onset of 11 years (6 to 16), and 57.1% were females. Females had a greater prevalence of autoimmune diseases (60.6% vs 34.4%, p<0.001). Thyroid disease was most prevalent (41%, 153/374), especially in females (51.6% vs 26.9%), and the prevalence of 1 or more autoimmune disease was 49.3% (184/374). Autoimmune disease was associated with lower odds of cardiovascular disease (CVD)-odds ratio [OR] 0.61, 95% confidence interval [CI] 0.37 to 1.00 for thyroid autoimmune disease and OR 0.34 (95% CI 0.12 to 0.93) for nonthyroid autoimmune disease, both compared to those without autoimmune disease (p=0.033). Autoimmune diseases were not associated with the presence of nephropathy, neuropathy or retinopathy. CONCLUSIONS Lifetime risk of autoimmune disease in longstanding T1D approaches 50%, is greater in females and is driven by thyroid disease. The probability of diabetes complications, such as CVD, was lower in those with autoimmune disease, which was driven mostly by nonthyroid autoimmune diseases.
Collapse
Affiliation(s)
- Nancy Cardinez
- Division of Endocrinology and Metabolism, Department of Medicine, Sinai Health System, University of Toronto, Toronto, Ontario, Canada
| | - Leif E Lovblom
- Division of Endocrinology and Metabolism, Department of Medicine, Sinai Health System, University of Toronto, Toronto, Ontario, Canada
| | - Andrej Orszag
- Division of Endocrinology and Metabolism, Department of Medicine, Sinai Health System, University of Toronto, Toronto, Ontario, Canada
| | - David Z I Cherney
- Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Bruce A Perkins
- Division of Endocrinology and Metabolism, Department of Medicine, Sinai Health System, University of Toronto, Toronto, Ontario, Canada.
| |
Collapse
|
|
43
|
Gad H, Saraswathi S, Al-Jarrah B, Petropoulos IN, Ponirakis G, Khan A, Singh P, Al Khodor S, Elawad M, Almasri W, Abdelrahman H, Hussain K, Hendaus MA, Al-Mudahka F, Abouhazima K, McGrogan P, Malik RA, Akobeng AK. Corneal confocal microscopy demonstrates minimal evidence of distal neuropathy in children with celiac disease. PLoS One 2020; 15:e0238859. [PMID: 32956371 PMCID: PMC7505458 DOI: 10.1371/journal.pone.0238859] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES The aim of this study was to utilise corneal confocal microscopy to quantify corneal nerve morphology and establish the presence of sub-clinical small fibre damage and peripheral neuropathy in children with celiac disease. METHODS This is a cross-sectional cohort study of twenty children with celiac disease and 20 healthy controls who underwent clinical and laboratory assessments and corneal confocal microscopy. Corneal nerve fiber density (no.mm2), corneal nerve branch density (no.mm2), corneal nerve fiber length (mm.mm2), corneal nerve fiber tortuosity and inferior whorl length (mm.mm2) were quantified manually. RESULTS Corneal nerve fiber density (34.7±8.6 vs. 32.9±8.6; P = 0.5), corneal nerve branch density (47.2±24.5 vs. 47.3±20.0; P = 0.1) and corneal nerve fiber length (20.0±5.1 vs. 19.5±4.5; P = 0.8) did not differ between children with celiac disease and healthy controls. Corneal nerve fiber tortuosity (11.4±1.9 vs 13.5±3.0; P = 0.01) was significantly lower and inferior whorl length (20.0±5.5 vs 23.0±3.8; P = 0.06) showed a non-significant reduction in children with celiac disease compared to healthy controls. Inferior whorl length correlated significantly with corneal nerve fiber density (P = 0.005), corneal nerve branch density (P = 0.04), and corneal nerve fiber length (P = 0.002). CONCLUSION Corneal confocal microscopy demonstrates minimal evidence of neuropathy in children with celiac disease.
Collapse
Affiliation(s)
- Hoda Gad
- Department Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Saras Saraswathi
- Division of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha, Qatar
| | - Bara Al-Jarrah
- Division of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha, Qatar
| | | | | | - Adnan Khan
- Department Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Parul Singh
- Research Department, Sidra Medicine, Doha, Qatar
| | | | - Mamoun Elawad
- Division of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha, Qatar
| | - Wesam Almasri
- Division of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha, Qatar
| | - Hatim Abdelrahman
- Division of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha, Qatar
| | | | | | - Fatma Al-Mudahka
- Division of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha, Qatar
| | - Khaled Abouhazima
- Division of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha, Qatar
| | - Paraic McGrogan
- Division of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha, Qatar
| | - Rayaz A. Malik
- Department Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
- Institute of Cardiovascular Medicine, University of Manchester, Manchester, United Kingdom
| | - Anthony K. Akobeng
- Division of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha, Qatar
| |
Collapse
|
|
44
|
Alsaheel AY, Alayed SI, Alotaibi YM, Alfahhad AA, Alothman OM, Alnefaie HF. Mean glycosylated hemoglobin in children with type 1 diabetes at King Fahad Medical City, Riyadh, Saudi Arabia. J Family Community Med 2020; 27:163-167. [PMID: 33354146 PMCID: PMC7745789 DOI: 10.4103/jfcm.jfcm_173_20] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/22/2020] [Accepted: 08/24/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND: Type 1 diabetes is the third most common chronic disease among teenagers. In Saudi Arabia, there is a gap of knowledge regarding hemoglobin A1C (HbA1c) concentration levels, and adherence to regular follow-up visits by patients. The aim of this study was to determine the mean glycosylated hemoglobin (HbA1c) levels in diabetic children who have been diagnosed with type 1 diabetes and were being followed up at a tertiary care center in Saudi Arabia. MATERIALS AND METHODS: This cross-sectional study was conducted among all diabetic children treated at King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia. Data were retrieved and analysed during the period from September to December 2018. Diabetic patients of <18 years and who were being followed up at KFMC were included in the study. Data on age, sex, duration of illness, associated comorbidities, antidiabetic regimen, and HbA1c levels were obtained. Student t-test was used to compare quantitative parameters between two groups, and Chi-square employed to test for associations between categorical variables at 5% significance level. RESULTS: A total of 510 patients of were included in the study; about 53% were females. The mean HbA1c level was 10.6% and females showed higher HbA1c levels. Data showed a strong correlation between age and HbA1c levels (P < 0.001), with older patients showing higher HbA1c levels. The HbA1c levels also increased as the duration of disease increased. The median number of patient visits to KFMC was two per year. No statistically significant differences were observeed for type of treatment for diabetes. Celiac disease, the most frequent comorbidity, was seen in 50% of patients. CONCLUSION: Diabetic children who were followed up at KFMC had high HbA1C level (10.6%), and lower than recommended follow-up visits per year. The treating physicians should educate patients and their legal guardians on the importance of follow-up visits and their role in controlling HbA1C levels, and following healthier lifestyle.
Collapse
Affiliation(s)
| | - Sulaiman I Alayed
- College of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Yazzan M Alotaibi
- College of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Aseel A Alfahhad
- College of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Othman M Alothman
- College of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Hissah F Alnefaie
- Saudi Center for Disease Control and Prevention, Riyadh, Saudi Arabia
| |
Collapse
|
|
45
|
Maloy MH, Ferrer MA, Parashurama N. In Vivo Differentiation of Stem Cell-derived Human Pancreatic Progenitors to Treat Type 1 Diabetes. Stem Cell Rev Rep 2020; 16:1139-1155. [PMID: 32844324 DOI: 10.1007/s12015-020-10018-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Type 1 diabetes mellitus (T1DM) is an autoimmune disease that results from the loss of the pancreatic β-cells. The autoimmune destruction of the β-cells causes the loss of insulin production from the islets of the pancreas, resulting in the loss of blood glucose regulation. This loss of regulation, if not treated, can lead to a plethora of long-term complications in patients. Subsequently, T1DM patients rely on the administration of exogenous insulin sources to maintain their blood glucose levels. In this review, we summarize the history of T1DM therapy and current treatment options. Although treatments for T1DM have progressed substantially, none of the available treatment options allow the patient to live autonomously. Therefore, the challenge to develop a therapy that will fully reverse the disease still remains. A promising field of T1DM therapies is cell replacement therapies derived from human pluripotent stem cells. Here, we specifically review studies that employ stem-cell derived pancreatic progenitors transplanted for in vivo differentiation/maturation and discuss, in detail, the complications that arise post transplantation, including heterogeneity, graft immaturity, and host foreign bodyresponse. We also discuss efforts to induce human stem cell-derived mature β-cells in vitro and compare strategies regarding transplantation of pancreatic progenitors versus mature β-cells cells. Finally, we review key approaches that address critical limitations of in vivo progenitor differentiation including vascularization, oxygenation, and transplant location. The field of islet replacement therapy has made tremendous progress in the last two decades. If the strengths and limitations of the field continue to be identified and addressed, future studies will lead to an ideal treatment for T1DM. Graphical abstract.
Collapse
Affiliation(s)
- Mitchell H Maloy
- Department of Chemical and Biological Engineering, University at Buffalo (State University of New York), 907 Furnas Hall, Buffalo, NY, 14260, USA
| | - Matthew A Ferrer
- Department of Chemical and Biological Engineering, University at Buffalo (State University of New York), 907 Furnas Hall, Buffalo, NY, 14260, USA
| | - Natesh Parashurama
- Department of Chemical and Biological Engineering, University at Buffalo (State University of New York), 907 Furnas Hall, Buffalo, NY, 14260, USA. .,Department of Biomedical Engineering, University at Buffalo, (State University of New York), 323 Bonner Hall, Buffalo, NY, 14260, USA. .,Clinical and Translation Research Center (CTRC), University at Buffalo (State University of New York), 875 Ellicott St, Buffalo, NY, 14203, USA.
| |
Collapse
|
|
46
|
An Overview of International Guidelines Focusing on the Long-Term Management of Coeliac Disease. GASTROINTESTINAL DISORDERS 2020. [DOI: 10.3390/gidisord2020016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Coeliac disease (CD) is an autoimmune disorder characterised by, but not isolated to, intestinal enteropathy in response to exposure to gluten in predisposed individuals. The mainstay of the management of CD is a strict, lifelong gluten free diet (GFD). Although numerous publications have focused on pathways to guide the diagnosis of CD, recommendations for the care of patients after diagnosis are less well established. This manuscript aimed to review the available published guidelines focusing on the ongoing management and follow-up of patients after diagnosis with CD and commencement of a GFD. All available guidelines recommend strict adherence to a GFD with most recommending an annual review by a specialist clinician, focusing on symptoms, adherence and growth. In addition to monitoring micronutrient status, some guidelines suggest monitoring bone mineral density in at-risk groups and screening for other autoimmune disorders. The benefit of multi-disciplinary input was outlined in many guidelines, in particular, the involvement of a specialist dietitian to provide nutritional counselling and support. While the available guidelines provide key messages, they highlight a lack of strong evidence and some inconsistences. Further evidence is required to support high quality, best-practice management strategies that will optimise the outcomes of patients with CD.
Collapse
|
|
47
|
Liu Y, Chen S, Zhang D, Li Z, Wang X, Xie X, Zhu H, Ren L, Wang L. The study on the risk of other endocrine glands autoimmune diseases in patients with type 1 diabetes mellitus. Medicine (Baltimore) 2020; 99:e20437. [PMID: 32481446 DOI: 10.1097/md.0000000000020437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
To study the changes of pancreas, thyroid, adrenal, parathyroid and gonadal organ-specific antibodies in patients with type 1 diabetic patients and to explore the risk of development to other endocrine gland autoimmune diseases.Fifty one patients with type 1 diabetes mellitus were selected. ELISA was used to detect islet, adrenal gland, Parathyroid, gonadal organ-specific antibody levels, the level of thyroid-related antibodies by lectrochemiluminescence.Compared with the healthy control group, the levels of the 17-α-OHAb, 21-OHAb, NALP5Ab, P450sccAb, and CaSRAb in the T1DM group were significantly higher. GADAb-positive patients were more likely to have TPOAb-positive patients than GADAb-negative patients, and the positive rate of 2 thyroid antibodies in GADAb-positive patients was significantly higher than that in GADAb-negative patients. The presence of these antibodies is related to the age of onset of type 1 diabetes or Patient age. In combination with 1 or 2 islet antibody-positive patients, the combined non-islet antibody positive rate was higher than that of islet antibody-negative patients.Patients with type 1 diabetes with other autoimmune diseases at risk significantly increased compared with normal, of which the most common thyroid autoimmune disease, thyroid antibodies and hormone levels should be routinely detected at the first visit and long-term follow-up.
Collapse
Affiliation(s)
- Yang Liu
- Department of Endocrinology, Hebei General Hospital
| | - Shuchun Chen
- Department of Endocrinology, Hebei General Hospital
- Department of Endocrinology
| | | | - Zelin Li
- Department of Endocrinology, Hebei General Hospital
- Department of Endocrinology
| | - Xing Wang
- Department of Endocrinology, Hebei General Hospital
| | - Xing Xie
- Department of Endocrinology, Hebei General Hospital
| | - Haijiao Zhu
- Department of Endocrinology, Hebei General Hospital
| | - Luping Ren
- Department of Endocrinology, Hebei General Hospital
| | - Liqin Wang
- Key Laboratory of Environment and Population Health of Hebei Province, Department of Epidemiology and Statistics, Hebei Medical University, Shijiazhuang, Hebei, PR China
| |
Collapse
|
|
48
|
Kakleas K, Basatemur E, Karavanaki K. Association Between Severity of Diabetic Ketoacidosis at Diagnosis and Multiple Autoimmunity in Children With Type 1 Diabetes Mellitus: A Study From a Greek Tertiary Centre. Can J Diabetes 2020; 45:33-38.e2. [PMID: 32800761 DOI: 10.1016/j.jcjd.2020.05.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 05/05/2020] [Accepted: 05/06/2020] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Type 1 diabetes mellitus is a chronic disorder associated with development of autoimmunity. In this work, we studied the relationship between severity of acidosis at diagnosis and future risk for autoimmunity development in children with type 1 diabetes. METHODS We investigated the presence of associated autoimmunity in 144 children with type 1 diabetes (mean ± standard deviation: age, 12.44±4.76 years; diabetes duration, 4.41±3.70 years). We identified the presence of thyroid disease, celiac disease, autoimmune gastritis and adrenal autoimmunity, and retrospectively reviewed the files for presence of diabetic ketoacidosis at diagnosis. RESULTS Autoimmunity prevalence was 16.7% for thyroid autoimmunity, 9.5% for celiac disease, 5% for gastric autoimmunity and 8.0% for multiple autoimmunities. There were strong associations between severe acidosis at diabetes diagnosis (pH<7.10) and development of thyroid autoimmunity (odds ratio [OR], 5.34; 95% confidence interval [CI], 1.90‒15.1; p<0.001), celiac disease (OR, 5.83; 95% CI, 1.19‒28.6; p=0.013), gastric autoimmunity (OR, 13.1; 95% CI, 1.22‒140; p=0.006) and multiple autoimmunity (OR, 26.7; 95% CI, 2.36‒301; p<0.01). The associations persisted after adjustment for sex, age at diabetes diagnosis, age at assessment, time since diabetes diagnosis and antiglutamic acid decarboxylase autoantibody status. CONCLUSIONS The severity of acidosis at diagnosis is strongly associated with the development of associated autoimmune diseases in children with type 1 diabetes and could act as a predictive factor for multiple autoimmunity development. This association can be either due to effect of acidosis on immune system or to the presence of a more aggressive diabetes endotype.
Collapse
Affiliation(s)
- Kostas Kakleas
- Paediatric Department, Leicester Royal Infirmary, Leicester, United Kingdom.
| | - Emre Basatemur
- Population, Policy and Practice Programme, Institute of Child Health, University College of London, London, United Kingdom
| | - Kyriaki Karavanaki
- Diabetic Clinic, Second Department of Pediatrics, University of Athens, "P&A Kyriakou" Children's Hospital, Athens, Greece
| |
Collapse
|
|
49
|
Abbade RCF, Fernandes A, Zantut-Wittmann DE, Parisi MCR, Pavin EJ. Type 1 diabetes mellitus associated or not with primary hypothyroidism and women's fertility. Gynecol Endocrinol 2020; 36:126-130. [PMID: 31232118 DOI: 10.1080/09513590.2019.1631282] [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] [Indexed: 10/26/2022] Open
Abstract
The aim of this study is to evaluate the prevalence of infertility and other reproductive parameters in women with type 1 diabetes mellitus (DM1) with and without primary hypothyroidism (PH). This is a cross-sectional study conducted at Division of Endocrinology. We evaluated 110 female, aged over 18 years, 79 had DM1 and 31 had DM1 plus PH. They were interviewed to obtain data on their gynecological and obstetric history; medical charts were reviewed to determine the characteristics of the diseases and to assess clinical/laboratory data. Infertility was defined as 12 months of unprotected sexual intercourse without conception. We used the chi-square and Mann-Whitney's tests, and logistic regression analysis. The prevalence of infertility in the total sample was 24.5%, no differences were found between groups regarding obstetric outcomes and gynecologic variables. Factors associated with infertility were microvascular complication (OR: 11.36; 95% CI: 2.488-52.632; p = .029), polycystic ovary syndrome (OR: 9.80; 95% CI: 2.247-43.478; p = .016), PH (OR: 3.38; 95% CI: 1.078-10.638; p = .047), and older age at onset of DM1 (OR: 1.12; 95% CI: 1.029-1.215; p = .019). The presence of PH in women with DM1 was a predictive factor for infertility. Women with DM1 showed poorer reproductive outcomes compared to the general population.
Collapse
Affiliation(s)
- Randolfo Carlos Ferraz Abbade
- Endocrinology Division of Department of Clinical Medicine, School of Medical Sciences, University of Campinas, São Paulo, Brazil
| | - Arlete Fernandes
- Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, São Paulo, Brazil
| | | | - Maria Candida Ribeiro Parisi
- Endocrinology Division of Department of Clinical Medicine, School of Medical Sciences, University of Campinas, São Paulo, Brazil
| | - Elizabeth João Pavin
- Endocrinology Division of Department of Clinical Medicine, School of Medical Sciences, University of Campinas, São Paulo, Brazil
| |
Collapse
|
|
50
|
Abstract
Diabetes mellitus (DM) is the most common endocrine and metabolic disease caused by absolute or insufficient insulin secretion. Under the context of an aging population worldwide, the number of diabetic patients is increasing year by year. Most patients with diabetes have multiple complications that severely threaten their survival and living quality. DM is mainly divided into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). T1DM is caused by absolute lack of insulin secretion, so the current treatment for T1DM patients is exogenous insulin replacement therapy. At present, exercise therapy has been widely recognized in the prevention and treatment of diabetes, and regular aerobic exercise has become an important part of T1DM treatment. At the same time, exercise therapy is also used in conjunction with other treatments in the prevention and treatment of diabetic complications. However, for patients with T1DM, exercise still has the risk of hypoglycemia or hyperglycemia. T1DM Patients and specialist physician need to fully understand the effects of exercise on metabolism and implement individualized exercise programs. This chapter reviews the related content of exercise and T1DM.
Collapse
Affiliation(s)
- Xiya Lu
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Cuimei Zhao
- Department of Cardiology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| |
Collapse
|