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?