Post on 23-Dec-2015
Ronald E. LaPorte
Janice Dorman, Ph.D.DirectorMolecular Epidemiology
Ronald LaPorte, Ph.D.DirectorDisease Monitoring and Telecommunications
WHO CollaboratingCenter
GSPH
The Importance of Type 1Registries
Diabetes Epidemiology Team in Pittsburgh
• Allan Drash, M.D.• Dorothy Becker, M.D.• Janice Dorman, Ph.D.• Lewis Kuller, M.D., Dr.PH• Ronald LaPorte, Ph.D.• Trevor Orchard, M.D.• Thomas Songer, Ph.D.• Massimo Trucco, M.D.
Type I Diabetes the Epidemiologist’sDream Disease
Easy to DiagnosisFrequent but not too frequentSevere but not too severeInsulinDynamic Epidemiology
Excess Mortality
0
1
2
3
4
5
6
7
8
9
Type I Type II
Chronic Diseases in Children
0
2
4
6
8
10
12
14
16
Type I CA CF MS JRA MD
• Identical Twins = 35%• HLA Identical = 18%• non asp 57 = 2%
PreventionPrevention
19701970
ICAICA
HLA BHLA B
Childhood diabetes
PreventionPrevention
Insulin AntibodiesInsulin Antibodies
HLA DRHLA DR
19801980 Type I diabetes
PreventionPrevention
HLA DQHLA DQ
19901990
CyclosporinCyclosporin
Insulin DependentDiabetes
PreventionPrevention
20202020
ICA 7873ICA 7873
T cell receptor GeneT cell receptor Gene
Growth Hormone TherapyGrowth Hormone Therapy
Name--Unknown
The Search for the Magic BulletThe Search for the Magic Bulletto Prevent Type I Diabetesto Prevent Type I Diabetes
PreventionPreventionof Type Iof Type I
Toxic!!!Toxic!!!
Let observations with extensive viewSurvey mankind from China to Peru
S. Johnson, 1749
The Environmental
in Preventing Diabetes
Challenge
Environmental Etiology of Type I diabetes
• Environmental agents causes disease in animals
• Geographic Variation• Temporal Variation• Migrants take on risk of new
environment• Environmental Factors Found to
Cause Disease in the Population
Prevention:
Reducing the incidence of disease
Last, Dictionary of Epidemiology
Environmental Etiology of Type I diabetes
• Environmental agents causes disease in animals
• Geographic Variation• Temporal Variation• Migrants take on risk of new
environment• Environmental Factors Found to
Cause Disease in the Population
Type I diabetes Incidence
FIN
SWD
NOR
UK
PLD
JPN
PRC
0 5 10 15 20 25 30 35
FIN
SWD
NOR
UK
PLD
JPN
PRC
Environmental Etiology of Type I diabetes
• Environmental agents causes disease in animals
• Geographic Variation• Temporal Variation• Migrants take on risk of new
environment• Environmental Factors Found to
Cause Disease in the Population
Allegheny County, PA
0
5
10
15
20
25
65-69 70-74 75-79 80-84 85-89
White Males
NW Males
US Virgin Islands
0
5
10
15
20
25
30
1979 1981 1983 1985 1987
Environmental Etiology of IDDM
• Environmental agents causes disease in animals
• Geographic Variation• Temporal Variation• Migrants take on risk of new
environment• Environmental Factors Found to
Cause Disease in the Population
Migration Effects
02468
10121416
Chinese Jewish French
Source Migrant
Asian Migration to UK
0
2
4
6
8
10
12
14
16
18
1972 1974 1976 1978 1980 1982 1984
English
Asian-English
A Public Health Approach Towards Prevention of IDDM
Green mountains range beyond the northern wall
White water rushes round the eastern town
right here is where, alone and restless, he
begins a journey of a thousand miles.
While travelers’ intents are fleeting clouds,
A friend’s affection is a setting sun.
He waves good-bye, and as he goes from here,
His dappled horse lets out a lonely neigh.
Where will the agent be found?
0
5
10
15
20
25
30
1979 1981 1983 1985 1987
The Importance of IDDM Registries
Establishment of Population Based Registries for 1990-99
• Diagnosed as IDDM• On Insulin at Hospital discharge• Diagnosed between 1/1/90 and
31/12/99• Age at onset 0-14• Member of a defined community• Secondary Source of Case
Identification
WHO DiaMond ProjectWHO DiaMond Project
WHO DiaMond ProjectWHO Multinational Project for Childhood DiabetesWHO Diabetes Mondiale
• 155 Centers• 70 Countries• 7.2% of the World’s
Children
16000 New Cases16000 New Cases
At China rate = 56 CasesAt China rate = 56 Cases
The south sweet,the north saltthe east pungentand the west sour
Chinese Academy ofPreventive Medicine
56 different Nationalities
WHO DiaMond ProjectWHO DiaMond Project
Yang ZeBeijing Hospital
To evaluate the incidence of IDDM in China
• Set up a collaborative registry network;
• Based on DiaMond standard protocol
• 22 Type 1 registry centers in China.
WHO DiaMond Project WHO DiaMond Project
A gracefully executed work
Jan Alice Lew
Yang Ze
Logistics of Registration
• Research Workers 233• Registry Sources 6• Hospitals 753• Schools 12557• Population covered
83,575,028• Population <15 yrs
20,659,472
Percent Ascertainment by Center
0
10
20
30
40
50
60
70
80
90
100
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Overall = 94.5%
Global Incidence of IDDM
0 5 10 15 20 25 30 35
FIN
CAN
SWD
SCOT
NOR
US
UK
DEN
PLD
Cuba
JPN
MEX
PRC
0 0.5 1 1.5 2
Geographic Variation Within China
Age at Onset
0
0.5
1
1.5
2
2.5
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Females
Males
North South variation
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
North South
Ethnic Group
0 0.5 1 1.5 2 2.5
Zhuang
Han
Man
Korean
Hui
Ulguir
Mongol
5-Fold
If one does not store up vital forces in the winter, he will be sure to suffer from an epidemic in the spring
Gulin
0
0.2
0.4
0.6
0.8
1
1.2
1.4
89 90 91 92 93 94
Tracking Down the Etiology of IDDM
Molecular Epidemiology Studies (WHO DiaMond, Jan Dorman)
Ecologic RelationshipsOutbreak InvestigationsCase-crossover design
Monitor Incidence
Chinese Migrants
0 0.5 1 1.5 2 2.5
PRC
Taiwan
Singapore
Hong K ong
4-fold
Public Health Prevention
• Monitor Incidence Rapidly• Identify Epidemics• Outbreak Investigations• Reduction of factor
Prevention
Identification of Identification of Precipitating FactorsPrecipitating Factors
Monitoring IDDM Monitoring IDDM IncidenceIncidence
Reduction of Reduction of Precipitating FactorsPrecipitating Factors
Prevention
Diabetes Epidemiology
InformationSuperhighway
Talking Points
• We know more about the incidence of Type 1 diabetes than any chronic disease. Why cannot we find the environmental factor?
• Type 1 diabetes is increase in almost all countries, what might be driving this?
• The Pattern of Type 1 diabetes is virtually the same as rheumatic fever, the early part of the center. Why does this give us hope to find its cause?
Review Questions (Developed by the Supercourse team)
• Why is Type 1 diabetes considered to be a “dream disease” for epidemiologists•For 30 years we have been told that the cure to type 1 diabetes is around the corner, while Type 1 diabetes has never been prevented. Why?•Epidemiology of Type 1 diabetes typically focuses on incidence, and type 2 on prevalence, Why?