Changing trends in epidemiology of type 1 diabetes mellitus throughout

the world: How far have we come and where do we go from here

Ingrid Libman, M.D., Ph.D.

Ronald LaPorte, Ph.D.

University of Pittsburgh

Objectives

* Counting diabetes: Historical background

* Diabetes Registries: What have we learned?

* Challenges ahead: Where do we go from here?

Objectives

* Counting diabetes: Historical background

* Diabetes Registries: What have we learned?

* Challenges ahead: Where do we go from here?

Need to count disease, specifically diabetes,

started a long time ago……..

Counting diabetes: Why is it important?

Reducing the incidence of disease (primary prevention)

Reducing the prevalence of disease (secondary prevention)

PreventionPrevention

ControlControlOngoing operations or programs aimed at reducing the incidence and/or prevalence of

diseaseLast, Dictionary of Epidemiology

Counting diabetes…

Galen, disciple of HippocratesSecond century AD

…“diarrhea of the urine”….. “the thirsty disease”…

…“rare”….…“only seen two cases”…..

Aretaeus the CappadocianDisciple of Hippocrates

Second century AD

….“Diabetes is a wonderful affection, not very frequent among men, being a melting

down of the flesh and limbs into urine”……

…”the patient is short-lived if the constitution of the disease be completely established”…

Maimonides1135-1204 AD

…”diabetes seldom seen in cold Europeand frequently encountered in warm Africa”…

…” have not seen in the West”……” here, in Egypt, in the course of 10 years,

I have seen more than twenty peoplewho suffer this illness”….

Historical background

End of 1970’s

* Types of diabetes loosely divided into “juvenile onset” and “maturity onset”

* Enormous variation in cut-off values for the fasting glucose level and after OGTT

* Size of glucose load varied between 50 g and 100 gr or body weight related

Historical background

* Chemical diabetes: no symptoms of diabetes, normal fasting glucose, but demonstrable abnormality of oral glucose tolerance test

* Studies done* small number of children * different doses of glucose administered * different criteria for defining abnormal glucose tolerance (USPHS, Fajans and Conn, University Diabetes Group Program, etc)

Book summarizing contributions, clinical and population-based on the subject of

diabetes epidemiology and highlighted the many gaps in our diabetes epidemiology

knowledge at that time

Kelly West, 1978 "Epidemiology of Diabetes

and its Vascular Complications"

It took many centuries….

                                     

“A survey of twenty diabetologists revealed that they employ diagnostic criteria differing quite substantially.

In some populations, including the general population of the United States, these disparities would result in very major differences in the rates of "diabetes." Under certain

common circumstances, some diabetologists would classify as normal more than half of the one- and two-hour values

considered to be abnormal by other well-qualified diabetologists”

Substantial differences in the diagnostic criteria used by diabetes experts

KW WestDiabetes 1975

Historical background

1979 & 1980

* IDDM and NIDDM defined

* 75 gr oral glucose tolerance test (OGTT) became the gold standard with fasting and 2 hour values defined

* Category of IGT added (metabolic stage intermediate between normal glucose homeostasis and diabetes)

Diabetes in childhood = IDDM

the epidemiologist’s “dream”

Easy to diagnose Abrupt onset Requiring medical attention Requiring medication (insulin)

By the 1980’s …..

* Few registries monitoring IDDM incidence

* Limited information but geographical differences in incidence identified

* However, lack of standardization:- different case definition- different ages- different degrees of ascertainment

“Registries of Persons with IDDM”(International Workshop on

the Epidemiologyof IDDM)

1983 *An international collaborative IDDM registry group should be established to develop standardized norms

*Validation of the completeness of case ascertainment should be required

*Investigators should share their patient intake forms

*Plan for sharing of data between registries should be established

LaPorte R et al. Diabetes Care 1985

Diabetes in Childhood: IDDM Registries

Establishment of population-based registries around the world

Monitor the global pattern of the disease

Provide a basis for standardized studies of risk factors

Karvonen M et al. Diabetes Care 2000

Argelia, Argentina, Antigua, Australia, Austria, Bahamas, Barbados, Belgium, Brazil, Bulgaria, Chile, China, Colombia, Costa Rica, Croatia, Cuba, Czech Republic, Denmark, Dominica, Dominican Republic, Egypt, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, Iceland, India, Ireland, Israel, Italy, Japan, Korea, Kuwait, Lithuania, Malta, Mauritius, Mexico, Netherlands, New Zealand, Norway, Paraguay, Peru, Poland, Portugal, Romania, Russia, Saint Kitts, Slovakia, Slovenia, Spain, Sudan, Sweden, Switzerland, Taiwan, Tanzania, Thailand, Tunisia, United Kingdom, Uruguay, USA, Venezuela

DIAMOND ProjectCountries participating

DIAMOND ProjectAlgeria: Dr. K. Bessaoud (Oran). Argentina: Dr. M. Molinero de Ropolo (Cordoba); Dr. M. de Sereday, M.L. Marti, Dr. M. Damiano, and Dr. M. Moser (Avellaneda); Dr. S. Lapertosa (Corrientes), Dr. A. Libman (Rosario), Dr. O. Ramos (Buenos Aires). Australia: Dr. C. Verge and Dr. N. Howard (New South Wales). Austria: Dr. E. Schober. Barbados: Dr. O. Jordan. Belgium: Dr. I. Weets, Dr. C. Vandevalle, Dr. I. De Leeuw, Dr. F. Gorus, Dr. M. Coeckelberghs, and Dr. M. Du Caju (Antwerp region). Brazil: Dr. L. J. Franco and Dr. S.R.G. Ferreira (3 centers, state of Sao Paulo). Bulgaria: Dr. R. Savova and Prof. V. Christov (West Bulgaria) and Dr. V. Iotova and Prof. Valentina Tzaneva (Varna). Canada: Dr. E. Toth (Alberta) and Dr. M.H. Tan (Prince Edward Island). Chile: Dr. E. Carrasco and Dr. G. Lopez (Santiago). China: Dr. Yang Ze (Henan, Dalian, Guilin, Jilin, Nanning, and Zunyi); Dr. Bo Yang (Tieling); Dr. Chen Shaohua and Dr. Fu Lihua (Jinan); Dr. Deng Longqi (Sichuan); Dr. Shen Shuixian (Shanghai); Dr. Teng Kui (Wulumuqi); Dr. Wang Chunjian, Dr. H. Jian, and Dr. J. Ju (Zhengzhou); Dr. Yan Chun and Dr. Y. Ze (Beijing); Dr. Deng Yibing and Dr. Li Cai (Changchun); Dr. Ying-Ting Zhang (Jilin province); Dr. Liu Yuqing and Dr. Long Xiurong (Shenyang); Dr. Zhaoshou Zhen (Huhehot); Dr. Zhiying Sun (Dalian); Prof. Wang Binyou (Harbin); and Dr. Gary Wing-Kin Wong (Hong Kong). Colombia: Dr. P. Aschner (Santafè de Bogotà, D.C.). Cuba: Dr. O. Mateo de Acosta, Dr. I. Hernández Cuesta, Dr. F. Collado Mesa, and Dr. O. Diaz-Diaz. Denmark: Dr. B.S. Olsen, Dr. A.J. Svendsen, Dr. J. Kreutzfeldt, and Dr. E. Lund (4 counties). Dominica: Dr. E.S. Tull. Estonia: Dr. T. Podar. Finland: Prof. J. Tuomilehto and Dr. M. Karvonen. France: Dr. C. Levy-Marchal and Dr. P. Czernichow (4 regions). Germany: Dr. A. Neu (Baden-Wuerttemberg). Greece: Dr. C. Bartsocas, Dr. K. Kassiou, Dr. C. Dacou-Voutetaki, Dr. A.C. Kafourou, Dr. Al Al-Qadreh, and Dr. C. Karagianni (Attica region). Hungary: Dr. Gyula Soltesz (18 counties). Israel: Prof. Z. Laron, Dr. O. Gordon, Dr. Y. Albag, and Dr. I. Shamis. Italy: Dr. F. Purrello, Dr. M. Arpi, Dr. G. Fichera, Dr. M. Mancuso, and Dr. C. Lucenti (eastern Sicily); Prof. G. Chiumello (Lombardia region); Dr. G. Bruno and Prof. G. Pagano (Turin province); Dr. M. Songini, Dr. A. Casu, Dr. A. Marinaro, Dr. R. Ricciardi, Dr. M.A. Zedda, and Dr. A. Milia (Sardinia); Dr. M. Tenconi and Dr. G. Devoti (Pavia province); Prof. P. Pozzilli, Dr. N. Visalli, Dr. L. Sebastiani, Dr. G. Marietti, and Dr. R. Buzzetti (Lazio region); and Dr. V. Cherubini (Region Marche). Japan: Dr. A. Okuno, Dr. S. Harada, and Dr. N. Matsuura (Hokkaido); Dr. E. Miki, Dr. S. Miyamoto, and Dr. N. Sasaki (Chiba); and Dr. G. Mimura (Okinawa). Kuwait: Dr. A. Shaltout and Dr. Mariam Qabazrd. Latvia: Dr. G. Brigis. Lithuania: Dr. B. Urbonaite. Luxembourg: Dr. C. de Beaufort. Mauritius: Dr. H. Gareeboo. Mexico: Dr. O. Aude Rueda (Veracruz). The Netherlands: Dr. M. Reeser (5 regions). New Zealand: Dr. R. Elliott (Auckland) and Dr. R. Scott, Dr. J. Willis, and Dr. B. Darlow (Canterbury). Norway: Dr. G. Joner (8 counties). Pakistan: Dr. G. Rafique (Karachi). Paraguay: Dr. J. Jimenez, Dr. C.M. Palaeios, Dr. F. Canete, Dr. J. Vera, and Dr. R. Almiron. Peru: Dr. S. Seclén (Lima). Poland: Dr. D. Woznicka, Dr. P. Fichna (Wielkopolska) and Dr. Z. Szybinski (Cracow). Portugal: Dr. C. Menezes (Portalegre), Dr. E.A. Pina (Algarve region), Dr. M.M.A. Ruas and Dr. F.J.C. Rodrigues (Coimbra), and Dr. S. Abreu (Madeira Island). Romania: Dr. C. Ionescu-Tirgoviste (Bucharest region). Russia: Dr. E. Shubnikof (Novosibirsk). Slovakia: Dr. D. Michalkova. Slovenia: Prof. C. Krzisnik, Dr. N. Bratina-Ursic, Dr. T. Battelino, and Dr. P. Brcar-Strukelj. Spain: Dr. A. Goday, Dr. C. Castell, and Dr. C. Lloveras (Catalonia). Sudan: Dr. M. Magzoub (Gezira province). Sweden: Prof. G. Dahlquist. Tunisia: Dr. K. Nagati (Kairouan) and Dr. F.B. Khalifa (Gafsa, Beja, Monastir). U.K.: Dr. A. Burden and N. Raymond (Leicestershire); Dr. B.A. Millward and Dr. H. Zhao (Plymouth); Dr. C.C. Patterson, Dr. D. Carson, and Prof. D. Hadden (N. Ireland); Dr. P. Smail and Dr. B. McSporran (Aberdeen); and Dr. P. Bingley (Oxford region). U.S.: Dr. E.S. Tull (Virgin Islands), Dr. R.E. LaPorte and Dr. I. Libman (Allegheny County, PA), Dr. J. Roseman and Dr. S.M. Atiqur Rahman (Jefferson County, AL), Dr. T. Frazer de Llado (Puerto Rico), and Dr. R. Lipton (Chicago). Uruguay: Dr. A.M. Jorge (Montevideo). Venezuela: Dr. P. Gunczler and Dr. R. Lanes (Caracas, second center), Dr. H. King (WHO, Geneva, Switzerland).

Historical background

late 1990’s

* Type 1 and type 2 diabetes defined

* Lowered criteria for diagnosis of diabetes to fasting plasma glucose 126 mg/dl

* Category of IFG added (plasma glucose 110 mg/dl and < 126 mg/dl)

Objectives

* Counting diabetes: Historical background

* Diabetes Registries: What have we learned?

* Challenges ahead: Where do we go from here?

“One of the fundamental necessities of cancer surveillance is for users of cancer information to be assured that case definitions, data collection, is standardized. This enables compilation of case-specific information into useful and meaningful registers. It also enables meaningful comparison of data across different registries”

North American Association of Central Cancer Registries

IDDM Registries: Eligibility Criteria

diagnosis of “IDDM” by a physician

on insulin at time of discharge from the hospital

age at onset 0-14

resident of a defined area at diagnosis

diabetes not secondary to other conditions

IDDM Registries: Data to be collected

Name Sex Race Birth Date Date of first insulin injection Place of residence at diagnosis

Validation of the completeness of case ascertainment: Capture-recapture method

Hospitals

Physicians

Schools

Pharmacies

Incidence of T1DM in the Americas 0 – 14 years – DIAMOND Project

0 5 10 15 20 25

Peru

Paraguay

Mexico

Cuba

Chile

Venezuela

Colombia

Barbados

Argentina

Brasil

Uruguay

USA

Canada

/100,000

Karvonen M et al. Diabetes Care 2000

Important geographic differences

T1DM Incidence in Santiago, Chile 1986 - 2000

0 1 2 3 4 5

2000

1997

1994

1991

1988

1986

/100,000

Carrasco E et al. Diabetes et Metabolism 2003 p<0.001

25

30

35

40

45

50

55

1987 1988 1989 1990 1991 1992 1993 1994 1995 1996

Years

1-4 years

4-9 years

10-14years

Incidence of T1DM in FinlandChildren < 15 years, 1987-1996

Tuomilehto et al. Diabetologia 1999

100,000/year

Relative increase in incidence of T1DM Children 0 - 14 years

0

1

2

3

4

5

6

7

8

9

10 United Kingdom

Hungary

Hawaii

China

Slovakia

Norway

Finland

USA Allegheny

Sweden

Lithuania

Estonia

Yearly change: 2.5 % per year (2.3-2.7)

Adapted from Onkamo P et al, Diabetologia 1999

Increase in the incidence%/year

Important temporal changes

Allegheny County IDDM RegistryIncidence by race and period, 1965 - 1994,

0-19 years age group

0

5

10

15

20

1965-69

1970-74

1975-79

1980-84

1985-89

1990-94

Whites

Blacks

/100,000

Libman I et al. Diabetes Care 1998

Allegheny County IDDM RegistryIncidence by race and period, 1965-1994,

15-19 years age group

0

5

10

15

20

25

30

35

1965-69

1970-74

1975-79

1980-84

1985-89

1990-94

Whites

Blacks

/100,000

*

**

Libman I et al. Diabetes Care 1998

IDDM incidence by periodBlacks – 10 to 14 years

0

5

10

15

20

25

30

Chicago Philadelphia

1985-1989

1990-1994

/100,000

Lipton R et al.Diabetes/Metab Res Rev 2002Lipman T et al. Diabetes Care 2002

Objectives

* Counting diabetes: Historical background

* Diabetes Registries: What have we learned?

* Challenges ahead: Where do we go from here?

At present…

2000….

* Type 1 and type 2 diabetes defined

* Type 2 diabetes in children described

* Reports of “double”, “hybrid”, “atypical”

diabetes (mixed phenotype)

* Changes in the phenotype of typical T1DM

Diabetes in childhood IDDM

the epidemiologist’s “challenge”

Easy to diagnose Abrupt onset Requiring medical attention Requiring medication (insulin)

X

Diabetes in Childhood

Efforts such as DIAMOND and EURODIAB should continue