Part XI Type 1 Diabetes
|
|
- Gabriella Whitehead
- 5 years ago
- Views:
Transcription
1 Part XI Type 1 Diabetes
2 Introduction Åke Lernmark Epidemiology Type 1 diabetes is increasing worldwide and shows epidemic proportions in several countries or regions [1]. There is evidence to suggest that the annual increase in type 1 diabetes incidence may amount to 2% to 7% dependent on the country or region [1]. In a Swedish countrywide study in 1983 to 1998, it was found that the incidence of type 1 diabetes had not increased but rather shifted to a younger age at diagnosis the 0- to 34-year age group [2]. In a similar study of Belgian patients up to 40 years of age, the rising incidence in children was largely restricted to boys under age 10, where the incidence more than doubled during the 15-year period [3]. At the same time obesity-related hyperglycemia appears to attain epidemic proportion [4]. It is controversial, however, to what extent an increase in body mass index increases the risk for type 1 diabetes [5]. The trend toward a younger age at onset is increasing the risk for ketoacidosis and cerebral edema in conjunction with the clinical onset of hyperglycemia. Genetic Etiology Type 1 diabetes can be diagnosed at any age. The genetic and environmental determinants as well as the clinical course are heterogeneous by age. The common pathway (Fig. XI.1) begins with genetic risk. It is remarkable that about 85% of newly diagnosed type 1 diabetes children or young adults have a first-degree relative (parent or sibling) with the disease [1]. The genetic factors represent primarily human leukocyte antigen (HLA) DR-DQ on chromosome 6 (Table XI.1). The HLA genetic factors may account for about 60% of the genetic risk for type 1 diabetes [4]. The HLA genotypes listed in Table XI.1 would typically account for about 90% of children and young adults developing diabetes. The Å. Lernmark Professor of Experimental Diabetes, Department of Clinical Sciences, Lund University/CRC, University Hospital MAS, Malmö, Sweden T.F. Davies (ed.), A Case-Based Guide to Clinical Endocrinology, C Humana Press, Totowa, NJ
3 322 Å. Lernmark INITIATORS - virus? - diet? PROMOTERS - genes? - virus? - diet? Genetic risk Autoimmunity Diabetes Fig. XI.1 Type 1 diabetes pathophysiology. Children are born with genetic risk primarily conferred by HLA DR-DQ genetic factors on chromosome 6. Initiators are thought to trigger the development of islet autoimmunity, which is marked by autoantibodies against insulin, the 65-kd isoform of glutamic acid decarboxylase (GAD65) or IA-2. Genetic factors, virus infections, or diet may represent promoters of islet autoimmunity eventually resulting in hyperglycemia DR4-DQA DQB /DR3-DQA DQB genotype (abbreviated DR4-DQ8/DR3-DQ2) is conferring the highest risk for type 1 diabetes in most countries. In North America and in Europe this high-risk genotype may be found among about 30% of the patients compared to 3% to 4% of the controls. The younger the patient, the higher the frequency of this genotype. The second highest risk genotype is DR4-DQA DQB1 0302/DR4-DQA DQB (DR4-DQ8 homozygous), the frequency of which is 25% to 27% compared to about 3% to 4% among controls. These and the other HLA genotypes listed in Table XI.1 are therefore necessary but not sufficient for type 1 diabetes. Table XI.1 Genetic factors affecting the risk of type 1 diabetes Genetic factor Chromosome Contribution to risk Reference HLA DR-DQ genotypes 6p21 Major [5] DR4-DQA DQB /DR3-DQA DQB DR4-DQA DQB1 0302/DR4-DQA DQB DR4-DQA DQB /DR8-DQA DQB DR3-DQA DQB1 0201/DR3-DQA DQB DR4-DQA DQB /DR4-DQA DQB DR4-DQA DQB /DR12-DQA DQB DR4-DQA DQB /DR13-DQA DQB DR4-DQA DQB1 0302/DR4-DQA DQB DR4-DQA DQB /DR9-DQA DQB DR3-DQA DQB1 0201/DR9-DQA DQB Non-HLA genetic factors Minor [5] INS 11p15 CTLA4 2q33 PTPN22 1p13 IL2RA 10p15 IFIH1 2q24 ITPR3 6p Non-HLA genetic regions Minor Unknown 12q Unknown 16p
4 Part XI Type 1 Diabetes 323 Table XI.2 Virus implicated in the development of islet autoimmunity, type 1 diabetes, or both Virus Type RNA/DNA Coxsackie Enterovirus RNA Echo Enterovirus RNA Rubella Rubivirus RNA Mumps Paroxyvirus RNA Rota Reovirus RNA Cytomegalovirus Herpesvirus DNA Ljungan virus Parechovirus RNA It is speculated that the interaction between these HLA genetic determinants and environmental factors such as certain virus may trigger islet autoimmunity (Fig. XI.1). Islet autoimmunity is marked by the appearance of islet autoantibodies (Table XI.2) to insulin (IAA), GAD65 (GADA) or IA-2 (IA-2A) [5]. The ability to develop these autoantibodies is related to the HLA genotype. Hence, IAA and IA-2A are more common among subjects who are positive for DR4-DQ8, while GADA is more likely to be found among DR3-DQ2 positive subjects. Several non-hla genetic factors (Table XI.1) have been identified either by association in case-control studies or by linkage analyses of affected sib-pairs [4]. The non-hla genetic factors may contribute to age at onset or the presence of islet autoantibodies, increasing the risk of low-risk HLA DR-DQ genotypes. For example, IAA occurs more often in subjects with a high-risk INS genotype [5], while the genetic polymorphism of the PTPN22 gene is increasing the risk for type 1 diabetes in subjects with low-risk HLA genotypes [4]. It will be important to determine to what extent the non-hla genes contribute to islet autoimmunity, as may be the case for the INS gene [4], or represent promoters of the pathogenic process leading to hyperglycemia. Etiologic Factors Virus infection remains the major environmental candidate to trigger islet autoimmunity, onset of hyperglycemia, or both. Several viruses have been implicated (Table XI.2). The association between virus and type 1 diabetes is primarily based on studies carried out at the clinical diagnosis of type 1 diabetes [1]. Several authors are therefore questioning whether virus infections in conjunction with the onset of hyperglycemia rather represent a promoter phenomenon of islet autoimmunity than a trigger of type 1 diabetes. Longitudinal studies of children at genetic risk for type 1 diabetes, such as The Diabetes Autoimmunity Study in the Young (DAISY), The Baby Diabetes study (BABY DIAB), The Diabetes Prevention Project (DIPP), and The Environmental Determinants of Diabetes in the Young (TEDDY) [5], may identify virus infections resulting in islet autoimmunity as marked by the appearance of islet autoantibodies [5].
5 324 Å. Lernmark Table XI.3 Diagnostic thresholds for diabetes and lesser degrees of glucose dysregulation Category FPG 2-hour PG after OGTT Normal 100 mg/dl (5.6 mmol/l) 140 mg/dl (7.8 mmol/l) IFG mg/dl ( mmol/l) IGT mg/dl ( mmol/l) Diabetes 126 mg/dl (7.0 mmol/l) 200 mg/dl (11.1 mmol/l) Note: When both tests are performed, IFG or IGT should be diagnosed only if diabetes is not diagnosed by the other test. A diagnosis of diabetes needs to be confirmed on a separate day. The table is from [1]. FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; OGTT, oral glucose tolerance test; PG, plasma glucose. Pathogenesis The preclinical beta-cell autoimmunity marked by IAA, GADA, and IA-2A, alone or in combination, may be present for several years before the onset of hyperglycemia. Islet autoantibody-positive subjects have varying degree of betacell dysfunction, particularly in their first-phase insulin response to intravenous glucose [4]. The presence of islet autoantibodies predicts type 1 diabetes by the number of autoantibodies; three autoantibodies that are persistently positive represent the highest risk, higher than any autoantibody alone or characteristics such as isotype, subtype, or epitope-specificity [5]. The islet autoantibodies are standardized, and proficiency tests have been instituted. Islet autoantibodies are used to enroll subjects to immune intervention trials [5]. Islet autoantibodies are the first primary end point in the TEDDY observational cohort study in which newborns who are younger than 4 months and have high-risk HLA genotypes in the general population or are first-degree relatives of patients affected with type 1 diabetes GADA, in particular, may be important to the differential classification of diabetes in adults to distinguish type 2 from type 1 or autoimmune diabetes [5]. Diagnostic Criteria The criteria to diagnose diabetes have remained the same with few modifications since the first recommendations were made in 1979 [1]. The diagnostic thresholds for fasting plasma glucose (FPG) and plasma glucose after a 75-g oral glucose tolerance test (OGTT) are summarized in (Table XI.3). Note also the thresholds for impaired fasting glucose (IFG) as well as impaired glucose tolerance (IGT). It is expected that an increasing number of subjects will be identified with any of the glycemic abnormalities shown in Table XI.3. There is considerable evidence that IFG, IGT, and, of course, diabetes are associated with increased morbidity including cardiovascular disease.
6 Part XI Type 1 Diabetes 325 Classification of Diabetes Once the diagnosis of hyperglycemia (IFG, IGT, or diabetes) has been made, the classification of disease is next. The classification of diabetes is complicated by the fact that symptoms not defined etiologic, pathogenic, or pathophysiologic criteria are used to classify the disease. In children, type 1 diabetes predominate. Type 1 diabetes is strongly associated with markers of autoimmune phenomena directed against the pancreatic beta-cells [3] and a loss of endogenous insulin production. In contrast to type 2 diabetes, type 1 diabetes is strongly associated with other organ-specific autoimmune disorders [3, 4]. Recent epidemiologic studies indicate that type 2 diabetes is rare among patients under 20 years of age. However, a major advance in molecular diagnosis has made it possible to classify diabetes into maturity-onset diabetes of the young (MODY), a dominantly inherited form of nonketotic diabetes [4]. MODY usually develops in childhood, adolescence, or young adulthood. However, despite the etiology, this disease is characterized by genetic and clinical heterogeneity. Type 2 diabetes genetic markers are beginning to be understood. Interestingly enough, most of the genetic factors identified so far seem to affect the beta-cell function [4]. Type 2 diabetes is strongly associated with obesity and an older age at onset, although current epidemiologic investigations suggest that also younger obese subjects may develop type 2 diabetes. Future Directions Current research efforts are focused on the identification of genetic and environmental determinants of the type 1 diabetes disease process and how they interact. The presentation of diabetes in children and adolescents is heterogeneous. Infants and preschool children, therefore, may be diagnosed at very different pathogenic stages. Children participating in screening studies for type 1 diabetes may be diagnosed by hyperglycemia. Diagnosis without the classic type 1 diabetes symptoms is possible, and ongoing and future studies will be important to establish possible beneficial effects on prognosis. Currently, after initiation of insulin replacement therapy, there is a transient, usually partial, remission. The remission, which is shorter in younger patients, is followed by complete insulin deficiency associated with acute and chronic complications and untimely death. Major research efforts, therefore, are focused on either preventing the development of hyperglycemia in islet autoantibody-positive subjects or intervening with the islet autoimmunity at the time of clinical diagnosis. Acknowledgments Studies in the author s laboratory is supported by the National Institutes of Health (grants DK26190, DK53004, AI42380, DK63861, DK17047), the American Diabetes Association, the Juvenile Diabetes Research Foundation, the Swedish Research Council, the Swedish Diabetes Association, the Skåne County Research and Development Fund, and the University Hospital Malmö Allmänna Sjukhus (UMAS) Fund.
7 326 Å. Lernmark References 1. Green A, Patterson CC. Trends in the incidence of childhood-onset diabetes in Europe Diabetologia 2001;44:B Pundziute-Lycka A, Dahlquist G, Nystrom L, et al. The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0 34 years group in Sweden Diabetologia 2002;45: Epub 2002 May Weets I, Rooman R, Coeckelberghs M, et al. The age at diagnosis of type 1 diabetes continues to decrease in Belgian boys but not in girls: a 15-year survey. Diabetes Metab Res Rev 2007;23: Onengut-Gumuscu S, Concannon P. Recent advances in the immunogenetics of human type 1 diabetes. Curr Opin Immunol 2006;18: Epub 2006 Aug Eisenbarth GS. Update in type 1 diabetes. J Clin Endocrinol Metab 2007;92:
LUP. Lund University Publications Institutional Repository of Lund University
LUP Lund University Publications Institutional Repository of Lund University This is an author produced version of a paper published in Diabetologia. This paper has been peer-reviewed but does not include
More informationINCIDENCE OF CHILDHOOD TYPE 1 DIABETES IN 14 EUROPEAN COUNTRIES INCLUDING ALL NORDIC COUNTRIES
INCIDENCE OF CHILDHOOD TYPE 1 DIABETES IN 14 EUROPEAN COUNTRIES 1989-1998 INCLUDING ALL NORDIC COUNTRIES FINLAND Sardinia SWEDEN NORWAY UK DENMARK ICELAND Estonia France Greece Italy Lithuania Latvia Romania
More information1. PATHOPHYSIOLOGY OF DIABETES MELLITUS
1. PATHOPHYSIOLOGY OF DIABETES MELLITUS Prof. Vladimir Palicka, M.D., Ph.D. Institute for Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove, Czech Republic Diabetes mellitus is
More informationEvgenija Homšak,M.Ph., M.Sc., EuSpLM. Department for laboratory diagnostics University Clinical Centre Maribor Slovenia
Evgenija Homšak,M.Ph., M.Sc., EuSpLM. Department for laboratory diagnostics University Clinical Centre Maribor Slovenia 14th EFLM Continuing Postgraduate Course in Clinical Chemistry and Laboratory Medicine
More informationLundgren, Markus; Lynch, Kristian; Larsson, Christer; Elding Larsson, Helena; Diabetes Prediction in Skåne study group; Carlsson, Annelie
Cord blood insulinoma-associated protein 2 autoantibodies are associated with increased risk of type 1 diabetes in the population-based Diabetes Prediction in Skane study Lundgren, Markus; Lynch, Kristian;
More informationIs there evidence for post-translational modification of beta cell autoantigens in the aetiology and pathogenesis of type 1 diabetes?
Is there evidence for post-translational modification of beta cell autoantigens in the aetiology and pathogenesis of type 1 diabetes? Lernmark, Åke Published in: Diabetologia DOI: 10.1007/s00125-013-3041-7
More informationWhat is New in Type 1 Diabetes? Prof. Åke Lernmark
What is New in Type 1 Diabetes? Lunds Universitet/CRC Skånes University Hospital SUS Malmö, Sweden 1 What s new in type 1 diabetes? Is the disease still increasing? What is the etiology? What is the pathogenesis?
More informationCase 2: A 42 year-old male with a new diagnosis of diabetes mellitus. History - 1
Case 2: A 42 year-old male with a new diagnosis of diabetes mellitus Bruce Knutsen, MD Michael Slag, MD Lisa Thomas, RN, CDE Essentia Health Diabetes and Endocrinology Conference October 14, 2011 History
More informationDiabetes Mellitus in the Pediatric Patient
Diabetes Mellitus in the Pediatric Patient William Bryant, M.D. Chief of Section Pediatric Endocrinology Children s Hospital at Scott & White Texas A&M University Temple, Texas Disclosures None Definitions
More informationClinical and Laboratory Characteristics of Childhood Diabetes Mellitus: A Single-Center Study from 2000 to 2013
Original Article www.cmj.ac.kr Clinical and Laboratory Characteristics of Childhood Diabetes Mellitus: A Single-Center Study from 2000 to 2013 Tae Hyun Park 1, Min Sun Kim 1,2, * and Dae-Yeol Lee 1,2 1
More informationDysregulation of glucose metabolism in preclinical type 1 diabetes
Pediatric Diabetes 2016: 17(Suppl. 22): 25 30 doi: 10.1111/pedi.12392 All rights reserved Pediatric Diabetes Review Article Dysregulation of glucose metabolism in preclinical type 1 diabetes Veijola R,
More informationPrediction and Prevention of Type 1 Diabetes. How far to go?
Prediction and Prevention of Type 1 Diabetes. How far to go? Peter Colman Diabetes and Endocrinology Royal Melbourne Hospital Royal Melbourne Hospital Lancet, Saturday 30 th November 1974; p. 1279-1282
More informationEarly Diagnosis of T1D Through An3body Screening
Early Diagnosis of T1D Through An3body Screening Andrea Steck, M.D. Barbara Davis Center for Childhood Diabetes Keystone Conference July 15, 2017 Presenter Disclosure Andrea Steck Disclosed no conflict
More informationEarly Indications of Type 1 Diabetes
Transcript Details This is a transcript of an educational program accessible on the ReachMD network. Details about the program and additional media formats for the program are accessible by visiting: https://reachmd.com/programs/clinicians-roundtable/early-indications-of-type-1-diabetes/3861/
More informationImmune therapy in type 1 diabetes mellitus.
Immune therapy in type 1 diabetes mellitus. Lernmark, Åke; Elding Larsson, Helena Published in: Nature Reviews Endocrinology DOI: 10.1038/nrendo.2012.237 2013 Link to publication Citation for published
More informationIslet Cell Autoantibodies in Cord Blood from Children with Blood Group Incompatibility or Hyperbilirubinemia
Autoimmunity, 2003 Vol. 36 (2), pp. 111 115 Islet Cell Autoantibodies in Cord Blood from Children with Blood Group Incompatibility or Hyperbilirubinemia A. MARIA ELFVING a, BENGT A. LINDBERG b, *, M. LANDIN-OLSSON
More informationIPS Modern management of childhood diabetes mellitus
Modern management of childhood diabetes mellitus Professor Philippe LYSY, MD PhD Pediatric endocrinology and diabetology Institut de Recherche Expérimentale et Clinique Université Catholique de Louvain
More informationType 1 diabetes in children - risk factors and prediction.
Type 1 diabetes in children - risk factors and prediction. Elding Larsson, Helena 2008 Link to publication Citation for published version (APA): Larsson, H. (2008). Type 1 diabetes in children - risk factors
More informationA Study on the Presence of Islets Cell Autoantibodies in Non- Insulin Requiring Young Diabetic Patients
IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-issn: 2279-0853, p-issn: 2279-0861.Volume 14, Issue 12 Ver. VI (Dec. 2015), PP 119-123 www.iosrjournals.org A Study on the Presence of Islets Cell
More informationReversion of b-cell Autoimmunity Changes Risk of Type 1 Diabetes: TEDDY Study DOI: /dc
Diabetes Care 1 Reversion of b-cell Autoimmunity Changes Risk of Type 1 Diabetes: TEDDY Study DOI: 10.2337/dc16-0181 Kendra Vehik, 1 Kristian F. Lynch, 1 Desmond A. Schatz, 2 Beena Akolkar, 3 William Hagopian,
More informationJanice Lazear, DNP, FNP-C, CDE DIAGNOSIS AND CLASSIFICATION OF DIABETES
Janice Lazear, DNP, FNP-C, CDE DIAGNOSIS AND CLASSIFICATION OF DIABETES Objectives u At conclusion of the lecture the participant will be able to: 1. Differentiate between the classifications of diabetes
More informationElimination of Dietary Gluten Does Not Reduce Titers of Type 1 Diabetes Associated Autoantibodies in High-Risk Subjects
Clinical Care/Education/Nutrition O R I G I N A L A R T I C L E Elimination of Dietary Gluten Does Not Reduce Titers of Type 1 Diabetes Associated Autoantibodies in High-Risk Subjects MICHAEL HUMMEL, MD
More informationType 1 Diabetes-Pathophysiology, Diagnosis, and Long-Term Complications. Alejandro J de la Torre Pediatric Endocrinology 10/17/2014
Type 1 Diabetes-Pathophysiology, Diagnosis, and Long-Term Complications Alejandro J de la Torre Pediatric Endocrinology 10/17/2014 Objectives Understand the pathophysiology of Type 1 diabetes. Be familiar
More informationProbiotics for the Prevention of Beta Cell Autoimmunity in Children at Genetic Risk of Type 1 Diabetes the PRODIA Study
Probiotics for the Prevention of Beta Cell Autoimmunity in Children at Genetic Risk of Type 1 Diabetes the PRODIA Study MARTIN LJUNGBERG, a RIITA KORPELA, b JORMA ILONEN, c JOHNNY LUDVIGSSON, a AND OUTI
More informationV. N. Karazin Kharkiv National University Department of internal medicine Golubkina E.O., ass. of prof., Shanina I. V., ass. of prof.
V. N. Karazin Kharkiv National University Department of internal medicine Golubkina E.O., ass. of prof., Shanina I. V., ass. of prof., Macharinskaya O.S., ass. of prof; Supervisor: prof. Yabluchanskiy
More informationDepleting T cells in newly diagnosed autoimmune (type 1) diabetes--are we getting anywhere?
Depleting T cells in newly diagnosed autoimmune (type 1) diabetes--are we getting anywhere? Lernmark, Åke Published in: Diabetes DOI: 10.2337/db13-1207 Published: 2013-01-01 Link to publication Citation
More informationChildhood Thyroid and Islet Autoimmunity. Immunogenetics, Risk Factors and Prediction
Childhood Thyroid and Islet Autoimmunity. Immunogenetics, Risk Factors and Prediction Jonsdottir, Berglind 2017 Document Version: Publisher's PDF, also known as Version of record Link to publication Citation
More informationDIABETES MELLITUS. IAP UG Teaching slides
DIABETES MELLITUS 1 DIABETES MELLITUS IN CHILDREN Introduction, Definition Classification, pathogenesis Clinical features Investigations and diagnosis Therapy and follow up Complications Carry home message
More informationType 2 Diabetes Mellitus in Adolescents PHIL ZEITLER MD, PHD SECTION OF ENDOCRINOLOGY DEPARTMENT OF PEDIATRICS UNIVERSITY OF COLORADO DENVER
Type 2 Diabetes Mellitus in Adolescents PHIL ZEITLER MD, PHD SECTION OF ENDOCRINOLOGY DEPARTMENT OF PEDIATRICS UNIVERSITY OF COLORADO DENVER Yes! Is Type 2 diabetes the same in kids as in adults? And No!
More informationBDC Keystone Genetics Type 1 Diabetes. Immunology of diabetes book with Teaching Slides
BDC Keystone Genetics Type 1 Diabetes www.barbaradaviscenter.org Immunology of diabetes book with Teaching Slides PRACTICAL Trailnet screens relatives and new onset patients for autoantibodies and HLA
More informationType 1 and Type 2 Diabetes among Youths in Jordan: Incidence and Trends for the period ( ) Abstract Acknowledgement 1.
Type 1 and Type 2 Diabetes among Youths in Jordan: Incidence and Trends for the period (2011-2016) Dr. Alghtani Fehaid Mohammed N Dr. Alanazi Saqqar Abdulelah S Dr. Alshahrani Adel Mohammed S Dr. Alhejaili
More informationIncreasing body mass index at diagnosis of diabetes in young adult people during in the Diabetes Incidence Study in Sweden (DISS).
Increasing body mass index at diagnosis of diabetes in young adult people during 1983-1999 in the Diabetes Incidence Study in Sweden (DISS). Littorin, Bengt; Nyström, L.; Gullberg, Bo; Råstam, Lennart;
More informationUniversità degli Studi di Chieti Clinica Pediatrica. M. Loredana Marcovecchio, Francesco Chiarelli
Università degli Studi di Chieti Clinica Pediatrica UP TO DATE SUL DIABETE M. Loredana Marcovecchio, Francesco Chiarelli Outline An update on T1D & T2D Epidemiology of diabetes Pathogenesis Treatment Complications
More informationAn association analysis of the HLA gene region in latent autoimmune diabetes in adults
Diabetologia (2007) 50:68 73 DOI 10.1007/s00125-006-0513-z SHORT COMMUNICATION An association analysis of the HLA gene region in latent autoimmune diabetes in adults M. Desai & E. Zeggini & V. A. Horton
More informationHLA-DR, HLA-DQB1 and PTPN22 gene polymorphism: association with age at onset for autoimmune diabetes
Clinical research HLA-DR, HLA-DQB1 and PTPN22 gene polymorphism: association with age at onset for autoimmune diabetes Anna Okruszko, Barbara Szepietowska, Natalia Wawrusiewicz-Kurylonek, Maria Górska,
More informationDiabetes Mellitus, Type 1 (or Insulin-Dependent Diabetes Mellitus)
Diabetes Mellitus, Type 1 (or Insulin-Dependent Diabetes Mellitus) Pronunciations: (di"ah-be'teez MEL-ih-tus ) Diabetes Mellitus is a chronic condition characterized either by lack of insulin secretion
More informationBuilding and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes
Received: 28 September 2016 Revised: 26 June 2017 Accepted: 10 July 2017 DOI: 10.1002/dmrr.2921 RESEARCH ARTICLE Building and validating a prediction model for paediatric type 1 diabetes risk using next
More informationb-cell Autoantibodies and Their Function in Taiwanese Children With Type 1 Diabetes Mellitus
ORIGINAL ARTICLE b-cell Autoantibodies and Their Function in Taiwanese Children With Type 1 Diabetes Mellitus Yi-Ching Tung, 1 Mei-Huei Chen, 2 Cheng-Ting Lee, 1 Wen-Yu Tsai 1 * Background/Purpose: To
More informationDistinguishing T1D vs. T2D in Childhood: a case report for discussion
Distinguishing T1D vs. T2D in Childhood: a case report for discussion Alba Morales, MD Associate Professor of Pediatrics Division of Pediatric Endocrinology and Diabetes Disclosure I have no financial
More informationChapter 11. Prediction of Type 1A Diabetes: The Natural History of the Prediabetic Period
Chapter 11 Prediction of Type 1A Diabetes: The Natural History of the Prediabetic Period Greenbaum et al Diabetes June 11, 212 Fall in C peptide During First 2 Years From Diagnosis: Evidence of at Least
More informationGAD65 Autoantibodies Detected by Electrochemiluminescence Assay Identify High Risk for Type 1 Diabetes
BRIEF REPORT GAD65 Autoantibodies Detected by Electrochemiluminescence Assay Identify High Risk for Type 1 Diabetes Dongmei Miao, K. Michelle Guyer, Fran Dong, Ling Jiang, Andrea K. Steck, Marian Rewers,
More informationShort communication. Abstract
Diabetologia (1999) 42: 574±578 Short communication Ó Springer-Verlag 1999 Immunological abnormalities in islets at diagnosis paralleled further deterioration of glycaemic control in patients with recent-onset
More informationIDDM1 and Multiple Family History of Type 1 Diabetes Combine to Identify Neonates at High Risk for Type 1 Diabetes
Metabolic Syndrome/Insulin Resistance Syndrome/Pre-Diabetes O R I G I N A L A R T I C L E IDDM1 and Multiple Family History of Type 1 Diabetes Combine to Identify Neonates at High Risk for Type 1 Diabetes
More informationPatients: Adult KPD patients (n 384) were followed longitudinally in a research clinic.
JCEM ONLINE Brief Report Endocrine Research Masked and Overt Autoantibodies Specific to the DPD Epitope of 65-kDa Glutamate Decarboxylase (GAD65- DPD) Are Associated With Preserved -Cell Functional Reserve
More informationPrediction and Prevention of Type 1 Diabetes
Prediction and Prevention of Type 1 Diabetes Helping to defuse the diabetes The number of people in the world currently with type 1 diabetes is around 17 million and increasing rapidly. Already there are
More informationJDRF Research. Jessica Dunne, Ph.D. Director, Discovery Research
JDRF Research Jessica Dunne, Ph.D. Director, Discovery Research Saturday, March 11, 2017 Hello JESSICA DUNNE, PH.D. Joined JDRF in September 2008, Lead for Prevention program since its inception in July
More informationAnti-islet autoantibodies in Japanese type 1 diabetes
15 th Korea Japan Symposium on Diabetes Anti-islet autoantibodies in Japanese type 1 diabetes Eiji Kawasaki, Katsumi Eguchi Nagasaki University Hospital, Nagasaki, Japan November 20 21, 21 2009 Cheju Islend
More informationAssociation of HLA-DQ Genotype in Autoantibody-Negative and Rapid-Onset Type 1 Diabetes
Pathophysiology/Complications O R I G I N A L A R T I C L E Association of HLA-DQ Genotype in Autoantibody-Negative and Rapid-Onset Type 1 Diabetes SHOICHIRO TANAKA, MD 1,2 TETSURO KOBAYASHI, MD 1 KOJI
More informationUnderstanding Autoimmune Diseases: Evolving Issues. Alvina D. Chu, M.D. April 23, 2009
Understanding Autoimmune Diseases: Evolving Issues Alvina D. Chu, M.D. April 23, 2009 Objectives Define the key pathogenic characteristics of: Type I diabetes mellitus Multiple sclerosis Rheumatoid arthritis
More informationStaging of Type 1 Diabetes: Clinical Implications. April Deborah Hefty, MN, RN, CDE.
Staging of Type 1 Diabetes: TT Clinical Implications April 2016 Deborah Hefty, MN, RN, CDE dhefty@benaroyaresearch.org BRI s major contributions to type 1 diabetes research Identified type 1 diabetes susceptibility
More informationASSESSMENT OF THE RISK FOR TYPE 1 DIABETES MELLITUS CONFERRED BY HLA CLASS II GENES. Irina Durbală
ASSESSMENT OF THE RISK FOR TYPE 1 DIABETES MELLITUS CONFERRED BY HLA CLASS II GENES Summary Irina Durbală CELL AND MOLECULAR BIOLOGY DEPARTMENT FACULTY OF MEDICINE, OVIDIUS UNIVERSITY CONSTANŢA Class II
More informationCeliac Disease: is it time for mass screening yet?
Celiac Disease: is it time for mass screening yet? Edwin Liu, MD Taplin Endowed Chair for Celiac Disease Director, Colorado Center for Celiac Disease Associate Professor of Pediatrics Digestive Health
More informationWe are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists. International authors and editors
We are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists 4,000 116,000 120M Open access books available International authors and editors Downloads Our
More informationKetoacidosis at diagnosis of type 1 diabetes: Effect of prospective studies with newborn genetic screening and follow up of risk children
Received: 30 January 2017 Revised: 5 April 2017 Accepted: 24 April 2017 DOI: 10.1111/pedi.12541 ORIGINAL ARTICLE Ketoacidosis at diagnosis of type 1 diabetes: Effect of prospective studies with newborn
More informationPathogenesis of Diabetes Mellitus
Pathogenesis of Diabetes Mellitus Young-Bum Kim, Ph.D. Associate Professor of Medicine Harvard Medical School Definition of Diabetes Mellitus a group of metabolic diseases characterized by hyperglycemia
More informationDOWNLOAD OR READ : TYPE I JUVENILE DIABETES PDF EBOOK EPUB MOBI
DOWNLOAD OR READ : TYPE I JUVENILE DIABETES PDF EBOOK EPUB MOBI Page 1 Page 2 type i juvenile diabetes type i juvenile diabetes pdf type i juvenile diabetes Diabetes means your blood glucose, or blood
More informationRisk of Pediatric Celiac Disease According to HLA Haplotype and Country
The new england journal of medicine original article Risk of Pediatric Celiac Disease According to HLA Haplotype and Country Edwin Liu, M.D., Hye-Seung Lee, Ph.D., Carin A. Aronsson, M.Sc., William A.
More informationNIH Public Access Author Manuscript N Engl J Med. Author manuscript; available in PMC 2015 January 03.
NIH Public Access Author Manuscript Published in final edited form as: N Engl J Med. 2014 July 3; 371(1): 42 49. doi:10.1056/nejmoa1313977. Risk of Pediatric Celiac Disease According to HLA Haplotype and
More informationEarly Onset of Diabetes in the Proband Is the Major Determinant of Risk in HLA. DR3-DQ2/DR4-DQ8 siblings, the
Diabetes Volume 63, March 2014 1041 Kathleen M. Gillespie, Rachel J. Aitken, Isabel Wilson, Alistair J.K. Williams, and Polly J. Bingley Early Onset of Diabetes in the Proband Is the Major Determinant
More informationCase- history. Lab results
Neda Rasouli, M.D. Associate Professor of Medicine Division of Endocrinology, UC Denver VA_ Eastern Colorado Health Care System Case- history 46 y/o AA male with BMI 37 presented in Oct 2001 with polyuria,
More informationRole of Insulin Resistance in Predicting Progression to Type 1 Diabetes
Pathophysiology/Complications O R I G I N A L A R T I C L E Role of Insulin Resistance in Predicting Progression to Type 1 Diabetes PING XU, MPH 1 DAVID CUTHBERTSON, MS 1 CARLA GREENBAUM, MD 2 JERRY P.
More informationAbstract. Keywords Type 1 diabetes, HLA-DQB1, Autoantibody, Finland, General population, Risk group.
Diabetologia (2003) 46:65 70 DOI 10.1007/s00125-002-0976-5 Signs of beta-cell autoimmunity and HLA-defined diabetes susceptibility in the Finnish population: the sib cohort from the Type 1 Diabetes Prediction
More informationComparison of the prevalence of islet autoantibodies according to age and disease duration in patients with type 1 diabetes mellitus
Original article http://dx.doi.org/10.6065/apem.2013.18.2.65 Ann Pediatr Endocrinol Metab 2013;18:65-70 Comparison of the prevalence of islet autoantibodies according to age and disease duration in patients
More informationARTICLE. Keywords HLA-DQB1 genotypes. Classification. C-peptide. Islet antibodies
Diabetologia (2006) 49: 1785 1794 DOI 10.1007/s00125-006-0293-5 ARTICLE E. Bakhtadze. H. Borg. G. Stenström. P. Fernlund. H. J. Arnqvist. A. Ekbom-Schnell. J. Bolinder. J. W. Eriksson. S. Gudbjörnsdottir.
More informationLymphoid tyrosine phosphatase (LYP/PTPN22) Arg620Trp variant regulates insulin autoimmunity and progression to type 1 diabetes
Diabetologia (2006) 49: 1198 1208 DOI 10.1007/s00125-006-0225-4 ARTICLE R. Hermann. K. Lipponen. M. Kiviniemi. T. Kakko. R. Veijola. O. Simell. M. Knip. J. Ilonen Lymphoid tyrosine phosphatase (LYP/PTPN22)
More informationTYPE 1 DIABETES MELLITUS: AUTOIMMUNE DIABETES
27 th Nov. 2015 TYPE 1 DIABETES MELLITUS: AUTOIMMUNE DIABETES Bo Kyung Koo CONTENTS 1. Introduction on Type 1 diabetes (T1DM) 2. Pathogenesis of T1DM 3. Immunologic Markers in T1DM 4. Atypical T1DM 1 Diabetes
More informationPathology of endocrine pancreas. By: Shifaa Alqa qa
Pathology of endocrine pancreas By: Shifaa Alqa qa major cell types: Beta ----- insulin Alpha ----- glucagon Delta ----- somatostatin PP (pancreatic polypeptide) cells ------ VIP DIABETES MELLITUS Normal
More informationAutoimmune Markers in Autoimmune Diabetes
Department of Molecular Medicine Molecular Immunogenetics Group Karolinska Institutet, Stockholm, Sweden Autoimmune Markers in Autoimmune Diabetes Manu Gupta Stockholm 2003 Manu Gupta All previously published
More information67 year-old Male with Flu-like Symptoms. Jess Hwang 12/6/12
67 year-old Male with Flu-like Symptoms Jess Hwang 12/6/12 HPI Fishing trip with son, had chills/fatigue 4 days later, went on business trip Severe nausea/vomiting x 2 days Found tachypneic, somnolent
More informationVariation in Glucose and A1c Measurement: Which Diabetes Test is Best?
Variation in Glucose and A1c Measurement: Which Diabetes Test is Best? Martha E Lyon, PhD, DABCC, FAACC Division of Clinical Biochemistry Department of Pathology & Laboratory Medicine Saskatchewan Health
More informationLessons from conducting research in an American Indian community: The Pima Indians of Arizona
Lessons from conducting research in an American Indian community: The Pima Indians of Arizona Peter H. Bennett, M.B., F.R.C.P. Scientist Emeritus National Institute of Diabetes and Digestive and Kidney
More information5/16/2018. Beyond Patient Centered to Personalized Diabetes Care: Disclosures. Research Support. Advisory Panel
Beyond Patient Centered to Personalized Diabetes Care Jennifer B. Marks, MD, FACP, FACE Emeritus Professor of Medicine University of Miami Miller School of Medicine Diabetes Research Institute Former Director,
More informationImmune Modulation of Type1 Diabetes
Immune Modulation of Type1 Diabetes Jay S. Skyler, MD, MACP Division of Endocrinology, Diabetes, and Metabolism and Diabetes Research Institute University of Miami Miller School of Medicine Ideal Therapeutic
More informationCorrespondence should be addressed to Jill M. Norris;
Clinical and Developmental Immunology Volume 2013, Article ID 417657, 8 pages http://dx.doi.org/10.1155/2013/417657 Clinical Study Evidence of Stage- and Age-Related Heterogeneity of Non-HLA SNPs and Risk
More information4. Definition and diagnostic criteria of diabetes mellitus type 1
4. Definition and diagnostic criteria of diabetes mellitus type 1 4.1. Definition of diabetes mellitus type1 Key question: What is diabetes mellitus type 1? Diabetes mellitus (DM) comprises a group of
More informationDOI: /j x. Published: Link to publication
Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden. Schölin, A.; Björklund,
More informationHeight growth velocity, islet autoimmunity and type 1 diabetes development: the Diabetes Autoimmunity Study in the Young
Diabetologia (2009) 52:2064 2071 DOI 10.1007/s00125-009-1428-2 ARTICLE Height growth velocity, islet autoimmunity and type 1 diabetes development: the Diabetes Autoimmunity Study in the Young M. M. Lamb
More informationDelay of Type I diabetes in high risk, first degree relatives by parenteral antigen administration: the Schwabing Insulin Prophylaxis Pilot Trial
Diabetologia (1998) 41: 536±541 Ó Springer-Verlag 1998 Delay of Type I diabetes in high risk, first degree relatives by parenteral antigen administration: the Schwabing Insulin Prophylaxis Pilot Trial
More informationHLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later
HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later Jensen, Richard A.; Agardh, Elisabet; Lernmark, Åke;
More informationX/00/$03.00/0 Vol. 85, No. 12 The Journal of Clinical Endocrinology & Metabolism Copyright 2000 by The Endocrine Society
0021-972X/00/$03.00/0 Vol. 85, No. 12 The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright 2000 by The Endocrine Society Prognostic Factors for the Course of Cell Function in
More informationBaseline heterogeneity in glucose metabolism marks the risk for type 1 diabetes and complicates secondary prevention.
Baseline heterogeneity in glucose metabolism marks the risk for type 1 diabetes and complicates secondary prevention. Elding Larsson, Helena; Larsson, Christer; Lernmark, Åke Published in: Acta Diabetologica
More informationDecline in Titers of Anti-Idiotypic Antibodies Specific to Autoantibodies to GAD65 (GAD65Ab) Precedes Development of GAD65Ab and Type 1 Diabetes.
Decline in Titers of Anti-Idiotypic Antibodies Specific to Autoantibodies to GAD65 (GAD65Ab) Precedes Development of GAD65Ab and Type 1 Diabetes. Elding Larsson, Helena; Jönsson, Ida; Lernmark, Åke; Ivarsson,
More informationWe are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists. International authors and editors
We are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists 3,350 108,000 1.7 M Open access books available International authors and editors Downloads Our
More informationT1D LANDSCAPE HLA INTERVENTION BIOMARKER SECONDARY PREVENTION BIG DATA GLOBAL RESEARCHERS VACCINE TIGEN-SPECIFIC TEDDY TRIAL NET RESEARCH TOOLS
ICROBIOME NOVEL DIAGNOSTICS OUTCOMES XSACKIE B VIRUSES COLLABORATIVE FUNDING ANDSCAPE EENING TOLERIZATION RIMARY PREVENTION PREVENTION LANDSCAPE A GUIDE FOR NAVIGATING EMERGING OPPORTUNITIES NOVEMBER 2014
More informationDiabetes Mellitus Due to Specific Causes: What s New?
Diabetes Mellitus Due to Specific Causes: What s New? George Grunberger, MD, FACP, FACE Chairman, Grunberger Diabetes Institute Clinical Professor, Internal Medicine and Molecular Medicine & Genetics Wayne
More informationRELATIONSHIP OF CLINICAL FACTORS WITH ADIPONECTIN AND LEPTIN IN CHILDREN WITH NEWLY DIAGNOSED TYPE 1 DIABETES. Yuan Gu
RELATIONSHIP OF CLINICAL FACTORS WITH ADIPONECTIN AND LEPTIN IN CHILDREN WITH NEWLY DIAGNOSED TYPE 1 DIABETES by Yuan Gu BE, Nanjing Institute of Technology, China, 2006 ME, University of Shanghai for
More informationCordoba 01/02/2008. Slides Professor Pierre LEFEBVRE
Cordoba 01/02/2008 Slides Professor Pierre LEFEBVRE Clinical Research in Type 2 Diabetes : Current Status and Future Approaches Pierre Lefèbvre* University of Liège Belgium Granada, Spain, February 2008
More informationIMI2 T1DM Call Topic Text: Translational approaches to disease modifying therapy of T1DM
IMI2 T1DM Call Topic Text: Translational approaches to disease modifying therapy of T1DM Dr Anke M Schulte, Head of Islet Biology Department Sanofi-Diabetes Frankfurt, Germany 11th of July, 2014 General
More informationPrognostic Accuracy of Immunologic and Metabolic Markers for Type 1 Diabetes in a High-Risk Population
Clinical Care/Education/Nutrition/Psychosocial Research O R I G I N A L A R T I C L E Prognostic Accuracy of Immunologic and Metabolic Markers for Type 1 Diabetes in a High-Risk Population Receiver operating
More informationWILL YOU USE HBA1C TO SCREEN & MONITOR DIABETES? Dr. Amany Mousa
WILL YOU USE HBA1C TO SCREEN & MONITOR DIABETES? Dr. Amany Mousa Diabetes is clinically well defined by glycation of proteins 1. True 2. false So far, diabetes has been defined as a clinical condition
More informationThe following pages constitute the final, accepted and revised manuscript of the article:
The following pages constitute the final, accepted and revised manuscript of the article: Larsson, H and Lynch, K and Lernmark, B and Nilsson, A and Hansson, G and Almgren, P and Lernmark, A and Ivarsson,
More informationRay A. Kroc & Robert L. Kroc. BDC Lectureship 2014
Ray A. Kroc & Robert L. Kroc BDC Lectureship 2014 Ray Kroc (Big Mack) 1902-1984 Predominant establisher of the McDonald's Corporation (1961) Philanthropist: Research and treatment of alcoholism, diabetes,
More informationIslet autoimmunity leading to type 1 diabetes develops
CLINICAL RESEARCH ARTICLE Impact of Age and Antibody Type on Progression From Single to Multiple Autoantibodies in Type 1 Diabetes Relatives Emanuele Bosi, 1 David C. Boulware, 2 Dorothy J. Becker, 3 Jane
More information39 year old F with sickle cell anemia presenting with pain crisis. Jess Hwang 11/8/12
39 year old F with sickle cell anemia presenting with pain crisis Jess Hwang 11/8/12 HPI Knee and back pain typical of usual crises Nausea and vomiting 2 days prior to admission Had previously been on
More informationPreventing the Predictable. Type 1 diabetes in children: Risk factors and impact of participation in prospective follow-up
Preventing the Predictable. Type 1 diabetes in children: Risk factors and impact of participation in prospective follow-up Lundgren, Markus 2017 Document Version: Förlagets slutgiltiga version Link to
More informationIslet autoantibody phenotypes and incidence in children at increased risk for type 1 diabetes
Diabetologia (1) 8:317 33 DOI 1.17/s1-1-367-y ARTICLE Islet autoantibody phenotypes and incidence in children at increased risk for type 1 diabetes Eleni Z. Giannopoulou 1 & Christiane Winkler 1, & Ruth
More informationBy: Dr. Doaa Khater Yassin, MM and M.D Paed Sr. specialist of Pediatrics SQUH
By: Dr. Doaa Khater Yassin, MM and M.D Paed Sr. specialist of Pediatrics SQUH Born SGA with birth weight of 2.4 kg, had IUGR Hospitalized at the age of 2 month with severe dehydration Diagnosed as DKA
More informationThe streetlight effect-is there light at the end of the tunnel?
The streetlight effect-is there light at the end of the tunnel? Lernmark, Åke Published in: Diabetes DOI: 10.2337/db15-0011 2015 Link to publication Citation for published version (APA): Lernmark, Å. (2015).
More informationIMIDIA IMPROVING BETA-CELL FUNCTION AND IDENTIFICATION OF DIAGNOSTIC BIOMARKERS FOR TREATMENT MONITORING IN DIABETES. A. Ktorza, B.
IMIDIA IMPROVING BETA-CELL FUNCTION AND IDENTIFICATION OF DIAGNOSTIC BIOMARKERS FOR TREATMENT MONITORING IN DIABETES A. Ktorza, B. Thorens DIABETES Definition Diabetes is a metabolic disease characterized
More informationDeterminants of outcome of children with type 1 diabetes in the North West Region of Cameroon
Out of the Department of Internal Medicine II - Grosshadern, Ludwig-Maximilians-Universität, Munich Determinants of outcome of children with type 1 diabetes in the North West Region of Cameroon Doctoral
More information