SlideShare a Scribd company logo
1 of 24
Download to read offline
Etiology of
Type 1 Diabetes Mellitus
Dr. Shashikiran Umakanth
Professor & Head
Department of Internal Medicine
Dr. TMA Pai Hospital - Udupi, MMMC
Manipal University, INDIA
Type 1 diabetes mellitus (T1DM)
 Characterized by absolute insulin deficiency
 Result of pancreatic beta cell destruction
 Prone to ketosis
Etiology of T1DM
Genetic
predisposition
Islet
autoimmunity
Dysglycemia Onset of
T1DM
Orban T et al. Diabetes Care 2009;32(12):2269-2274
 Environmental factors suggested by
 Seasonality
 Increasing incidence
 Epidemics of T1DM
 ? Viral infections
 Genetic factors alone cannot explain
etiology
 Genetic markers
 Can identify varying risk
 Poor positive predictive value in the
absence of autoantibodies
Environmental
Models for Pathogenesis of T1DM
van Belle TL, et al. Physiol Rev. 2011;91:79-118.
Atkinson MA. Diabetes. 2005;54:1253-1263.
▶ IAA - insulin autoantibodies
▶ GAD - glutamic acid
decarboxylase antibodies
▶ IA-2 (ICA512) - tyrosine
phosphatase antibodies
▶ ZnT8 - Zinc transporter 8
autoantibodies
▶ T cell assays - cellular
autoimmunity
Genetic factors in T1DM
HLA association with T1DM
 About 50% of genetic risk for T1DM attributed to
HLA region
 HLA-DR3/4 DQB1 genotype shown to be high-risk
for β-cell autoimmunity
 More than 50 genes associated with T1DM
 Dominant or recessive
 Low penetrance
Familial clustering
 Risk when first degree relatives have T1DM
Dizygous twin/
Non-twin sibling
8-15 %
Monozygous twin >50 % Father 12 %
Mother 6 %
Sibling with T1DM Parent with T1DM
Both parents
>30 %
>90 %*
10 %*
15 %*
15 %*
>75 %*
* For T2DM Warram. Genetics & Diabetes, Diabetes Information. Joslin Diabetes Center and Joslin Clinic
Environmental factors in T1DM
Geographic location
 Striking geographic variability
 0.73/100,000 in China
 60/100,000 in Finland
 Increasing incidence 3-5% per year
 More common in Northern
hemisphere
 Migrants from a low-incidence country have higher
incidence of the adopted country
 Example: South Asian children in UK
Borchers AT et al. The geoepidemiology of type 1 diabetes. Autoimmun Rev. 2010 Mar;9(5):A355-65.
Seasonal incidence
 In Northern hemisphere
 Incidence declines in warm summer months
 In Southern hemisphere
 Incidence declines in warm December-January
 ? Climatic factor, Vitamin D?
 ? Related to school attendance, viral infections?
Viruses
β-cell infection Systemic infection
Autoimmune β-cell damage
T1DM
Direct cytolytic
effects
Indirect immune effects
• Viral antigen
expression
• β-cell antigens altered
• HLA antigens or
cytokines expressed
• Activation of immune
response
• Breakdown of immune
tolerance
• Molecular mimicry with β-cell
antigens
Possible mechanisms for
virus-induced T1DM
Jun HS, Yoon JW. Diabetes Metab Res Rev. 2003 Jan-Feb;19(1):8-31
Type 1 Diabetes Mellitus - Etiology
Models for
etiopathogenesis of
T1DM
 T1DM may be a
relapsing-
remitting disease
van Belle TL, et al. Physiol Rev. 2011;91:79-118.
Models for
etiopathogenesis
of T1DM
 Fertile Field Hypothesis
 Time-window following a
viral infection
 Initial infection - normal T cell
response
 Subsequent - autoreactive T
cells
 Molecular mimicry
 Bystander activation
van Belle TL, et al. Physiol Rev. 2011;91:79-118.
Initial
infection
Subsequent
infection
Mejía-León ME, Barca AM. Nutrients. 2015 Nov 6;7(11):9171-84
Microbiome and Immune System
Other factors
 Gluten
 Cow’s milk
 Lack of sunshine - vitamin D deficiency
 Lack of breast feeding
 Drugs and food additives
 Vaccinations *
T1DM is increasing
0
10
20
30
40
50
60
70
1950 1960 1970 1980 1990 2000
Finland
Sweden
Colorado
Germany
Why is T1DM increasing?
 Reason not clear, but 3-5% per year rise in incidence
 Possibly due to
 Increased survival of T1DM individuals due to insulin
treatment
 Health promotion and increased life span, and potential to
have children
 Transmission of genetic susceptibility
Jaakko Tuomilehto. Curr Diab Rep (2013) 13:795–804
Summary
Overview & Screening
Genetic
predisposition Islet
autoimmunity
Dysglycemia Onset of
T1DM
Genetic
HLA class II
HLA class I
Non-HLA genes
Immunologic
IAA, GAD
IA-2 (ICA512),
ZnT8, T cell assays
Metabolic
IV GTT
OGTT
HbA1c
SCREENING
Orban T et al. Diabetes Care 2009;32(12):2269-2274
Taplin CE et al. Autoimmunity. 2008 Feb;41(1):11-8
The number of
antibodies, not the
individual antibody,
is most predictive of
progression to T1DM
Environmental
factors
Thank you
Questions
Question 1
 The most accepted etiology for T1DM is
A. Drug induced destruction of pancreatic β-cells
B. An environmental trigger activating autoimmunity in a
genetically susceptible individual
C. Vitamin D deficiency in countries that do not have
adequate exposure to sunlight
D. Obesity triggering hyperstimulation of pancreatic β-
cells causing their destruction
Question 2
 The most likely reason for rising incidence of
T1DM in most parts of the world is
A. Increasing vaccination coverage resulting in triggering
of autoimmunity in genetically susceptible individuals
B. Increasing vitamin D deficiency
C. Improved survival in T1DM with increased potential for
them to reproduce and transmit genetic susceptibility
D. Increased detection of T1DM patients due to advanced
diagnostic methods

More Related Content

What's hot

What's hot (20)

Diabetes mellitus an overview
Diabetes mellitus an overviewDiabetes mellitus an overview
Diabetes mellitus an overview
 
Pathophysiology and Classification of diabetes by Dr Selim
Pathophysiology and Classification of diabetes by Dr SelimPathophysiology and Classification of diabetes by Dr Selim
Pathophysiology and Classification of diabetes by Dr Selim
 
Diabetes Melliltus Complete (Introduction, Pathophysiology, Types, Diagnostic...
Diabetes Melliltus Complete (Introduction, Pathophysiology, Types, Diagnostic...Diabetes Melliltus Complete (Introduction, Pathophysiology, Types, Diagnostic...
Diabetes Melliltus Complete (Introduction, Pathophysiology, Types, Diagnostic...
 
Diabetes mellitus
Diabetes mellitus Diabetes mellitus
Diabetes mellitus
 
Diabetes powerpoint
Diabetes powerpointDiabetes powerpoint
Diabetes powerpoint
 
Diabetes
DiabetesDiabetes
Diabetes
 
Diabetes Powerpoint 6
Diabetes  Powerpoint 6Diabetes  Powerpoint 6
Diabetes Powerpoint 6
 
Type 2 Diabetes Mellitus - Pathophysiology
Type 2 Diabetes Mellitus - PathophysiologyType 2 Diabetes Mellitus - Pathophysiology
Type 2 Diabetes Mellitus - Pathophysiology
 
Diabetes
DiabetesDiabetes
Diabetes
 
diabetes
diabetesdiabetes
diabetes
 
Treatment of Diabetes Mellitus
Treatment of Diabetes MellitusTreatment of Diabetes Mellitus
Treatment of Diabetes Mellitus
 
Type 1 diabetes mellitus
Type 1 diabetes mellitusType 1 diabetes mellitus
Type 1 diabetes mellitus
 
Dibetties milliteus
Dibetties milliteusDibetties milliteus
Dibetties milliteus
 
Type 1 Diabetes
Type 1 Diabetes Type 1 Diabetes
Type 1 Diabetes
 
Diabetes Mellitus 1.pptx
Diabetes Mellitus 1.pptxDiabetes Mellitus 1.pptx
Diabetes Mellitus 1.pptx
 
2. diabetes mellitus
2. diabetes mellitus2. diabetes mellitus
2. diabetes mellitus
 
Diabetes
DiabetesDiabetes
Diabetes
 
Pathophysiology of diabetes mellitus
Pathophysiology of diabetes mellitusPathophysiology of diabetes mellitus
Pathophysiology of diabetes mellitus
 
Diabetes mellitus part-1
Diabetes mellitus part-1Diabetes mellitus part-1
Diabetes mellitus part-1
 
DIABETES MELLITUS an up-to-date 2017- 2018
DIABETES MELLITUS an up-to-date 2017- 2018DIABETES MELLITUS an up-to-date 2017- 2018
DIABETES MELLITUS an up-to-date 2017- 2018
 

Similar to Type 1 Diabetes Mellitus - Etiology

Immunology of Type I Diabetes: The Journey from Animal Models to Human Therap...
Immunology of Type I Diabetes: The Journey from Animal Models to Human Therap...Immunology of Type I Diabetes: The Journey from Animal Models to Human Therap...
Immunology of Type I Diabetes: The Journey from Animal Models to Human Therap...Apollo Hospitals
 
Autoimmunity&Food
Autoimmunity&FoodAutoimmunity&Food
Autoimmunity&Foodchlorine97
 
Gliadin, Intestinal Permeability, and Celiac Disease: From Innate Immunity to...
Gliadin, Intestinal Permeability, and Celiac Disease: From Innate Immunity to...Gliadin, Intestinal Permeability, and Celiac Disease: From Innate Immunity to...
Gliadin, Intestinal Permeability, and Celiac Disease: From Innate Immunity to...Letizia Saturni
 
Ctg underlying pathophysiology
Ctg underlying pathophysiologyCtg underlying pathophysiology
Ctg underlying pathophysiologyDr P Deepak
 
Cancer, alzheimers, diabetes – what do all have in common?
Cancer, alzheimers, diabetes – what do all have in common?Cancer, alzheimers, diabetes – what do all have in common?
Cancer, alzheimers, diabetes – what do all have in common?morwenna2
 
Diabetes Mellitus mekelle university
Diabetes Mellitus mekelle universityDiabetes Mellitus mekelle university
Diabetes Mellitus mekelle universityBirhanuAwtachew
 
changing courseoftype2diabetes
changing courseoftype2diabeteschanging courseoftype2diabetes
changing courseoftype2diabetesMunir Ahmad Mughal
 
Underlying pathophysiology in diabetes
Underlying pathophysiology in diabetesUnderlying pathophysiology in diabetes
Underlying pathophysiology in diabetesDr. Lin
 
Diabetes Diagnosis and Classification
Diabetes Diagnosis and ClassificationDiabetes Diagnosis and Classification
Diabetes Diagnosis and ClassificationDR. VIVEK ARYA
 
Ueda2015 diabetes control dr.lobna el-toony
Ueda2015 diabetes control dr.lobna el-toonyUeda2015 diabetes control dr.lobna el-toony
Ueda2015 diabetes control dr.lobna el-toonyueda2015
 
Ueda2015 diabetes control dr.lobna el-toony
Ueda2015 diabetes control dr.lobna el-toonyUeda2015 diabetes control dr.lobna el-toony
Ueda2015 diabetes control dr.lobna el-toonyueda2015
 

Similar to Type 1 Diabetes Mellitus - Etiology (20)

Immunology of Type I Diabetes: The Journey from Animal Models to Human Therap...
Immunology of Type I Diabetes: The Journey from Animal Models to Human Therap...Immunology of Type I Diabetes: The Journey from Animal Models to Human Therap...
Immunology of Type I Diabetes: The Journey from Animal Models to Human Therap...
 
Autoimmunity&Food
Autoimmunity&FoodAutoimmunity&Food
Autoimmunity&Food
 
Genetics to environment to T1DM by Dr Shahjada Selim
Genetics to environment to T1DM by Dr Shahjada SelimGenetics to environment to T1DM by Dr Shahjada Selim
Genetics to environment to T1DM by Dr Shahjada Selim
 
Gliadin, Intestinal Permeability, and Celiac Disease: From Innate Immunity to...
Gliadin, Intestinal Permeability, and Celiac Disease: From Innate Immunity to...Gliadin, Intestinal Permeability, and Celiac Disease: From Innate Immunity to...
Gliadin, Intestinal Permeability, and Celiac Disease: From Innate Immunity to...
 
Common variable immunodeficiency
Common variable immunodeficiencyCommon variable immunodeficiency
Common variable immunodeficiency
 
Diabetes mellitus
Diabetes mellitusDiabetes mellitus
Diabetes mellitus
 
Ctg underlying pathophysiology
Ctg underlying pathophysiologyCtg underlying pathophysiology
Ctg underlying pathophysiology
 
Cancer, alzheimers, diabetes – what do all have in common?
Cancer, alzheimers, diabetes – what do all have in common?Cancer, alzheimers, diabetes – what do all have in common?
Cancer, alzheimers, diabetes – what do all have in common?
 
Biomarkers in diabetes
Biomarkers in diabetesBiomarkers in diabetes
Biomarkers in diabetes
 
Type_1_DM_prevention_whats_new.pptx
Type_1_DM_prevention_whats_new.pptxType_1_DM_prevention_whats_new.pptx
Type_1_DM_prevention_whats_new.pptx
 
Diabetes Mellitus mekelle university
Diabetes Mellitus mekelle universityDiabetes Mellitus mekelle university
Diabetes Mellitus mekelle university
 
Dm 2
Dm 2Dm 2
Dm 2
 
Diabetes mellitus
Diabetes mellitusDiabetes mellitus
Diabetes mellitus
 
changing courseoftype2diabetes
changing courseoftype2diabeteschanging courseoftype2diabetes
changing courseoftype2diabetes
 
Underlying pathophysiology in diabetes
Underlying pathophysiology in diabetesUnderlying pathophysiology in diabetes
Underlying pathophysiology in diabetes
 
Final Project Abhishek
Final Project AbhishekFinal Project Abhishek
Final Project Abhishek
 
Diabetes Diagnosis and Classification
Diabetes Diagnosis and ClassificationDiabetes Diagnosis and Classification
Diabetes Diagnosis and Classification
 
Similarities between Type 1 Diabetes and Alopecia Areata
Similarities between Type 1 Diabetes and Alopecia AreataSimilarities between Type 1 Diabetes and Alopecia Areata
Similarities between Type 1 Diabetes and Alopecia Areata
 
Ueda2015 diabetes control dr.lobna el-toony
Ueda2015 diabetes control dr.lobna el-toonyUeda2015 diabetes control dr.lobna el-toony
Ueda2015 diabetes control dr.lobna el-toony
 
Ueda2015 diabetes control dr.lobna el-toony
Ueda2015 diabetes control dr.lobna el-toonyUeda2015 diabetes control dr.lobna el-toony
Ueda2015 diabetes control dr.lobna el-toony
 

More from Shashikiran Umakanth

COPD - Chronic Obstructive Pulmonary Disease
COPD - Chronic Obstructive Pulmonary DiseaseCOPD - Chronic Obstructive Pulmonary Disease
COPD - Chronic Obstructive Pulmonary DiseaseShashikiran Umakanth
 
Bronchial Asthma - Epidemiology, Pathogenesis and Management
Bronchial Asthma - Epidemiology, Pathogenesis and ManagementBronchial Asthma - Epidemiology, Pathogenesis and Management
Bronchial Asthma - Epidemiology, Pathogenesis and ManagementShashikiran Umakanth
 
Mendeley, Grammarly and Document Clouds for Thesis and Research Collaboration
Mendeley, Grammarly and Document Clouds for Thesis and Research CollaborationMendeley, Grammarly and Document Clouds for Thesis and Research Collaboration
Mendeley, Grammarly and Document Clouds for Thesis and Research CollaborationShashikiran Umakanth
 
Adding Life to Years, not just Years to Life!
Adding Life to Years, not just Years to Life!Adding Life to Years, not just Years to Life!
Adding Life to Years, not just Years to Life!Shashikiran Umakanth
 
Dengue Fever - Rational Management
Dengue Fever - Rational ManagementDengue Fever - Rational Management
Dengue Fever - Rational ManagementShashikiran Umakanth
 
Diabetes Mellitus - Patient Education in Kannada
Diabetes Mellitus - Patient Education in KannadaDiabetes Mellitus - Patient Education in Kannada
Diabetes Mellitus - Patient Education in KannadaShashikiran Umakanth
 
Novel approaches in Lipid Management
Novel approaches in Lipid ManagementNovel approaches in Lipid Management
Novel approaches in Lipid ManagementShashikiran Umakanth
 
Raising HDL cholesterol – The Controversy
Raising HDL cholesterol – The ControversyRaising HDL cholesterol – The Controversy
Raising HDL cholesterol – The ControversyShashikiran Umakanth
 

More from Shashikiran Umakanth (11)

COPD - Chronic Obstructive Pulmonary Disease
COPD - Chronic Obstructive Pulmonary DiseaseCOPD - Chronic Obstructive Pulmonary Disease
COPD - Chronic Obstructive Pulmonary Disease
 
Bronchial Asthma - Epidemiology, Pathogenesis and Management
Bronchial Asthma - Epidemiology, Pathogenesis and ManagementBronchial Asthma - Epidemiology, Pathogenesis and Management
Bronchial Asthma - Epidemiology, Pathogenesis and Management
 
Mendeley, Grammarly and Document Clouds for Thesis and Research Collaboration
Mendeley, Grammarly and Document Clouds for Thesis and Research CollaborationMendeley, Grammarly and Document Clouds for Thesis and Research Collaboration
Mendeley, Grammarly and Document Clouds for Thesis and Research Collaboration
 
Diabetes in Pregnancy
Diabetes in PregnancyDiabetes in Pregnancy
Diabetes in Pregnancy
 
Adding Life to Years, not just Years to Life!
Adding Life to Years, not just Years to Life!Adding Life to Years, not just Years to Life!
Adding Life to Years, not just Years to Life!
 
Dengue Fever - Rational Management
Dengue Fever - Rational ManagementDengue Fever - Rational Management
Dengue Fever - Rational Management
 
Diabetic Foot
Diabetic FootDiabetic Foot
Diabetic Foot
 
Diabetes Mellitus - Patient Education in Kannada
Diabetes Mellitus - Patient Education in KannadaDiabetes Mellitus - Patient Education in Kannada
Diabetes Mellitus - Patient Education in Kannada
 
GLP-1 and Diabetes Mellitus
GLP-1 and Diabetes MellitusGLP-1 and Diabetes Mellitus
GLP-1 and Diabetes Mellitus
 
Novel approaches in Lipid Management
Novel approaches in Lipid ManagementNovel approaches in Lipid Management
Novel approaches in Lipid Management
 
Raising HDL cholesterol – The Controversy
Raising HDL cholesterol – The ControversyRaising HDL cholesterol – The Controversy
Raising HDL cholesterol – The Controversy
 

Recently uploaded

Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu Medical University
 
Red Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfRed Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfMedicoseAcademics
 
pA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologypA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologyDeepakDaniel9
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfDolisha Warbi
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxNaveenkumar267201
 
Basic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxBasic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxkomalt2001
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsMedicoseAcademics
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfDolisha Warbi
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxMAsifAhmad
 
Adenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisAdenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisSujoy Dasgupta
 
BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE Mamatha Lakka
 
power point presentation of Clinical evaluation of strabismus
power point presentation of Clinical evaluation  of strabismuspower point presentation of Clinical evaluation  of strabismus
power point presentation of Clinical evaluation of strabismusChandrasekar Reddy
 
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationPhysiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationMedicoseAcademics
 
ayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptPradnya Wadekar
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets barmohitRahangdale
 
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D.  Bawankar.pptPharmacokinetic Models by Dr. Ram D.  Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D. Bawankar.pptRamDBawankar1
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project reportNARMADAPETROLEUMGAS
 

Recently uploaded (20)

Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu
 
Red Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfRed Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdf
 
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
 
pA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologypA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacology
 
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
 
Basic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxBasic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptx
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functions
 
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdfCONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
CONNECTIVE TISSUE (ANATOMY AND PHYSIOLOGY).pdf
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
 
American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...
 
Adenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisAdenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosis
 
BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE
 
power point presentation of Clinical evaluation of strabismus
power point presentation of Clinical evaluation  of strabismuspower point presentation of Clinical evaluation  of strabismus
power point presentation of Clinical evaluation of strabismus
 
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationPhysiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
 
ayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologypptayurvedic formulations herbal drug technologyppt
ayurvedic formulations herbal drug technologyppt
 
Role of Soap based and synthetic or syndets bar
Role of  Soap based and synthetic or syndets barRole of  Soap based and synthetic or syndets bar
Role of Soap based and synthetic or syndets bar
 
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D.  Bawankar.pptPharmacokinetic Models by Dr. Ram D.  Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project report
 

Type 1 Diabetes Mellitus - Etiology

  • 1. Etiology of Type 1 Diabetes Mellitus Dr. Shashikiran Umakanth Professor & Head Department of Internal Medicine Dr. TMA Pai Hospital - Udupi, MMMC Manipal University, INDIA
  • 2. Type 1 diabetes mellitus (T1DM)  Characterized by absolute insulin deficiency  Result of pancreatic beta cell destruction  Prone to ketosis
  • 3. Etiology of T1DM Genetic predisposition Islet autoimmunity Dysglycemia Onset of T1DM Orban T et al. Diabetes Care 2009;32(12):2269-2274  Environmental factors suggested by  Seasonality  Increasing incidence  Epidemics of T1DM  ? Viral infections  Genetic factors alone cannot explain etiology  Genetic markers  Can identify varying risk  Poor positive predictive value in the absence of autoantibodies Environmental
  • 4. Models for Pathogenesis of T1DM van Belle TL, et al. Physiol Rev. 2011;91:79-118. Atkinson MA. Diabetes. 2005;54:1253-1263. ▶ IAA - insulin autoantibodies ▶ GAD - glutamic acid decarboxylase antibodies ▶ IA-2 (ICA512) - tyrosine phosphatase antibodies ▶ ZnT8 - Zinc transporter 8 autoantibodies ▶ T cell assays - cellular autoimmunity
  • 6. HLA association with T1DM  About 50% of genetic risk for T1DM attributed to HLA region  HLA-DR3/4 DQB1 genotype shown to be high-risk for β-cell autoimmunity  More than 50 genes associated with T1DM  Dominant or recessive  Low penetrance
  • 7. Familial clustering  Risk when first degree relatives have T1DM Dizygous twin/ Non-twin sibling 8-15 % Monozygous twin >50 % Father 12 % Mother 6 % Sibling with T1DM Parent with T1DM Both parents >30 % >90 %* 10 %* 15 %* 15 %* >75 %* * For T2DM Warram. Genetics & Diabetes, Diabetes Information. Joslin Diabetes Center and Joslin Clinic
  • 9. Geographic location  Striking geographic variability  0.73/100,000 in China  60/100,000 in Finland  Increasing incidence 3-5% per year  More common in Northern hemisphere  Migrants from a low-incidence country have higher incidence of the adopted country  Example: South Asian children in UK Borchers AT et al. The geoepidemiology of type 1 diabetes. Autoimmun Rev. 2010 Mar;9(5):A355-65.
  • 10. Seasonal incidence  In Northern hemisphere  Incidence declines in warm summer months  In Southern hemisphere  Incidence declines in warm December-January  ? Climatic factor, Vitamin D?  ? Related to school attendance, viral infections?
  • 11. Viruses β-cell infection Systemic infection Autoimmune β-cell damage T1DM Direct cytolytic effects Indirect immune effects • Viral antigen expression • β-cell antigens altered • HLA antigens or cytokines expressed • Activation of immune response • Breakdown of immune tolerance • Molecular mimicry with β-cell antigens Possible mechanisms for virus-induced T1DM Jun HS, Yoon JW. Diabetes Metab Res Rev. 2003 Jan-Feb;19(1):8-31
  • 13. Models for etiopathogenesis of T1DM  T1DM may be a relapsing- remitting disease van Belle TL, et al. Physiol Rev. 2011;91:79-118.
  • 14. Models for etiopathogenesis of T1DM  Fertile Field Hypothesis  Time-window following a viral infection  Initial infection - normal T cell response  Subsequent - autoreactive T cells  Molecular mimicry  Bystander activation van Belle TL, et al. Physiol Rev. 2011;91:79-118. Initial infection Subsequent infection
  • 15. Mejía-León ME, Barca AM. Nutrients. 2015 Nov 6;7(11):9171-84 Microbiome and Immune System
  • 16. Other factors  Gluten  Cow’s milk  Lack of sunshine - vitamin D deficiency  Lack of breast feeding  Drugs and food additives  Vaccinations *
  • 17. T1DM is increasing 0 10 20 30 40 50 60 70 1950 1960 1970 1980 1990 2000 Finland Sweden Colorado Germany
  • 18. Why is T1DM increasing?  Reason not clear, but 3-5% per year rise in incidence  Possibly due to  Increased survival of T1DM individuals due to insulin treatment  Health promotion and increased life span, and potential to have children  Transmission of genetic susceptibility Jaakko Tuomilehto. Curr Diab Rep (2013) 13:795–804
  • 20. Overview & Screening Genetic predisposition Islet autoimmunity Dysglycemia Onset of T1DM Genetic HLA class II HLA class I Non-HLA genes Immunologic IAA, GAD IA-2 (ICA512), ZnT8, T cell assays Metabolic IV GTT OGTT HbA1c SCREENING Orban T et al. Diabetes Care 2009;32(12):2269-2274 Taplin CE et al. Autoimmunity. 2008 Feb;41(1):11-8 The number of antibodies, not the individual antibody, is most predictive of progression to T1DM Environmental factors
  • 23. Question 1  The most accepted etiology for T1DM is A. Drug induced destruction of pancreatic β-cells B. An environmental trigger activating autoimmunity in a genetically susceptible individual C. Vitamin D deficiency in countries that do not have adequate exposure to sunlight D. Obesity triggering hyperstimulation of pancreatic β- cells causing their destruction
  • 24. Question 2  The most likely reason for rising incidence of T1DM in most parts of the world is A. Increasing vaccination coverage resulting in triggering of autoimmunity in genetically susceptible individuals B. Increasing vitamin D deficiency C. Improved survival in T1DM with increased potential for them to reproduce and transmit genetic susceptibility D. Increased detection of T1DM patients due to advanced diagnostic methods

Editor's Notes

  1. Model for linear beta-cell mass decay. With genetic predisposition, an environmental trigger induces islet autoimmunity and beta-cell death leading to a sequence of prediabetic stages and eventually clinical onset.
  2. In this concept of T1D as a relapsing-remitting disease, dependent on cyclical disruption and restoration of the balance between effector and regulatory T cells and potentially counteracted by beta-cell proliferation. This model also provides a mechanistic rationale for its variable course.
  3. The fertile field hypothesis postulates the existence of a time window following viral infection during which at-risk individuals may develop autoimmunity. Infection with certain viruses temporarily create a fertile field. Whereas initial exposure to virus (e.g., via APC presentation; purple cells) will generate a normal antiviral response (green T cells), subsequent generation of autoreactive cells (red T cells) may occur via cross-reactivity with viral antigens (molecular mimicry) or direct recognition of autoantigens (bystander activation). Bystander activation is thought to be mediated by APC that process and present self-antigens, with the potential to raise autoreactive T cells only in the presence of viral “danger” signals.
  4. The lactate model appears to be the strongest possible explanation for understanding the link between T1DM and dysbiosis. According to this model, the presence of lactic acid- and butyrate-producing bacteria such as Prevotella and Akkermansia helps to maintain a healthy epithelium. This is because butyrate contributes to mucin synthesis and to the assembly of tight junctions. These bacteria were common in the microbiota of healthy children around the world. In contrast, when microorganisms such as Bacteroides and Veillonella are harbored in abundance, this substrate follows the pathway to succinate, acetate, and propionate. These products compromise mucin synthesis and increase paracellular permeability by altering the tight junctions. In addition, butyrate may contribute to maintaining the anti-inflammatory response in the healthy gut by inhibiting the activation of NF-κB. High-fiber diets have been associated with a decreased risk of inflammatory immune-related diseases. However, it is unknown whether this effect is due to the butyrate itself or to the associated microbial profile.
  5. Correct answer: B
  6. Correct answer: C