SPECIAL ARTICLE
WHO Multinational Project for Childhood Diabetes
Insulin-dependent diabetes mellitus (IDDM) is one of the most important chronic diseases of children worldwide. IDDM leads to an 8- to 10-fold excess risk of mortality in developed countries, whereas in developing countries, most cases die within a few years. A 60-fold international gradient in IDDM incidence has been reported, and epidemic periods have been identified. A new World Health Organization program, Multinational Project for Childhood Diabetes (Diabetes Mondiale or DIAMOND), has been developed to investigate and characterize global incidence, mortality, and health care. Over 10 yr (1990-1999), this study will collect population-based data concerning IDDM in >90 centers in 50 countries worldwide. The goals of DIAMOND are to collect standard information on incidence, risk factors, and mortality associated with IDDM; evaluate the efficiency and effectiveness of health care and the economics of diabetes; and establish national and international training programs in diabetes epidemiology. It is hoped that the DIAMOND project will be instrumental for the prevention of this serious disease and its sequelae. Diabetes Care 13:1062-68,1990
nsulin-dependent diabetes mellitus (IDDM) is one of the most important chronic diseases of children worldwide (1). In industrialized countries, it is among the most prevalent chronic childhood diseases. Although effective treatment is available, the burden to individuals and society is still high. Annual
I
This article was prepared for the WHO DIAMOND Project Group by Ronald E. LaPorte, laakko Tuomilehto, and Hilary King. Address correspondence and reprint requests to Ronald E. LaPorte, PhD, Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15213. Received for publication 5 February 1990 and accepted in revised form 10 April 1990.
1062
WHO DIAMOND Project Group
IDDM-related costs per diabetic individual in the United States approached $1000 in 1985, an expense well beyond the affordability of individuals or health-care systems in developing countries (2). IDDM often progresses to devastating life-threatening sequelae, e.g., amputation, blindness, and nephropathy. In developed countries, individuals with IDDM have an 8-10 times higher risk of dying prematurely than the nonaffected population (3). In developing countries, most IDDM patients die within a few years after diagnosis (4). It appears that IDDM incidence may be rising in many areas throughout the world (5), thus increasing the major health-care and economic burdens to society. There are considerable gaps in knowledge regarding the global patterns of the disease, host susceptibility, environmental risk factors, related morbidity and mortality, and health care and health economics of IDDM. The lack of information and standards for interpreting existing data impair the ability of the medical community to understand the impact of the disease. Moreover, effective public health measures cannot be developed without adequate data for their evaluation. Therefore, global efforts designed to understand this disease are critically needed. Because of the limited available information, a World Health Organization (WHO) Multinational Project for Childhood Diabetes (Diabetes Mondiale or DIAMOND) has been started. The objectives of this effort are to monitor the international patterns of IDDM incidence to the year 2000, provide a uniform basis for standardized studies of risk factors for IDDM, assess the mortality associated with the disease, evaluate health care (e.g., insulin availability) and health economics associated with diabetes, and develop training programs in diabetes research. This study presents a description of the goals of this project and its evolution.
DIABETES CARE, VOL. 13, NO. 10, OCTOBER 1990
WHO DIAMOND PROJECT GROUP
BACKGROUND The primary goal of the DIAMOND project is the collection of accurate population-based data concerning childhood diabetes worldwide. The accomplishment of this goal is dependent on a close cooperation among the participating centers and a standardized approach for data collection, reporting, and analysis. The evolution of the DIAMOND project began in the late 1970s with the establishment of the first multinational study of macrovascular disease associated with diabetes coordinated from the WHO (6). Considerable information has been gained from that study by examining the relationship of diabetes to heart disease. Of importance for the DIAMOND project was the demonstration that standardized data could be collected from many centers over an extended period of time. Based on this vanguard effort, it was clear that international epidemiological studies in diabetes were indeed feasible and very informative. In the early 1980s, interest in the epidemiology of IDDM began to flourish as the result of the recognition that the place where a child lives is one of the most important determinants of risk of diabetes (7). Moreover, there were indications of epidemic patterns of the disease (8) and a suggestion of a north-south gradient (9). These exciting within- and between-country comparisons pointed out the importance of cross-cultural studies and hence the need for standardization.
EVOLUTION OF INTERNATIONAL IDDM REGISTRY RESEARCH In 1983, a seminal meeting specific to IDDM epidemiology, sponsored by the Juvenile Diabetes Foundation, was held in Philadelphia. The participating scientists discussed the importance of establishing standardized registries to investigate the geographic and secular trends of IDDM. As a result of that meeting, standard criteria for IDDM registries were established, and an approach for international collaboration was adopted, leading to the birth of the Diabetes Epidemiology Research International (DERI) group (10). Also, it was recommended that more population-based registries be established. The DERI group represented a team of investigators who decided to collaborate to conduct standardized cross-cultural studies of IDDM that used population-based registries. At the 1985 International Diabetes Federation meeting in Madrid, a half-day session specifically related to IDDM registries was held. This was the first time that diabetes registries were formally discussed as part of an international congress. The participation of >50 scientists demonstrated the rapidly growing interest. Many of the participants went forward to establish registries in their own countries (11). The head of the WHO Division
DIABETES CARE, VOL. 13, NO. 10, OCTOBER 1990
of Noncommunicable Diseases was present at this meeting. Around this time, a link between pediatric endocrinologists and epidemiologists was formed. There was already an existing collaboration of the endocrinologists as part of the International Study Group on Diabetes. The pediatric endocrinologists and epidemiologists began discussing areas in which they could interface, and a strong liaison has been forged with a primary focus on registries. This has proved to be extremely beneficial for both groups, with the clinical input provided by the endocrinologists and the epidemiological design input provided by the epidemiologists. In 1986, at the International Symposium on the Epidemiology of Diabetes Mellitus, held in Bangkok, Thailand, a session focused on IDDM registries in Asia. More than 100 people were present, and WHO was officially represented. The Bangkok meeting proved to be very beneficial; scientists who were establishing IDDM registries shared their experiences, and others were inspired to develop studies in their countries. The report of the meeting was published in the Bulletin of the World Health Organization (12). Since the mid-1980s, there has been an exponential increase in the number of IDDM registries. As this occurred, it was evident that a central clearinghouse was needed to help foster collaboration and coordination of registry data. Therefore, in 1987, a WHO Collaborating Center for Diabetes Registries and Training was designated at the University of Pittsburgh. The mission of the center was to aid in the development and standardization of diabetes registries. The initial activity of the WHO center was to contact all researchers with existing IDDM registries. The. response from scientists with comparable incidence registries was remarkable, because all were willing to share their data for comparison purposes and agreed to be a part of the DERI group. A standardized reporting scheme was established for global surveillance, with aggregate data sent to the WHO Collaborating Center. This initial effort demonstrated that global surveillance was indeed feasible (13,14). The results of this collaboration underscored the importance of evaluating the reasons for the 60-fold difference in incidence across various countries. Moreover, some of the findings raised the alarming possibility of a global increase in IDDM incidence, in some cases of epidemic proportions (5,8). In 1988, the European Economic Community launched a study called EURODIAB. A portion of the program was designed to map the variation of IDDM in Europe, especially to investigate the observed northsouth incidence gradient. The EURODIAB study differed from the DERI group effort in that cases were enrolled prospectively, the data sent to the coordinating center consisted of individual records, and many of the registries concurrently collected blood samples. This represented a more extensive effort than that in the DERI group studies. This approach is most applicable in countries with advanced health-care systems. The initial
1063
CHILDHOOD DIABETES
funding for the effort will continue through mid-1991. Despite the structural differences between the DERI group and EURODIAB, both efforts use compatible definitions.of IDDM cases and defined population denominators. Therefore, the descriptive epidemiology from the two programs is directly comparable for the commonly collected variables and the common time period. Based on the rapid proliferation of standardized registries, evidence for extraordinary geographic differences in risk, and the evidence of a global increase in the incidence of this serious condition, plans for the establishment of the WHO Multinational Project for Childhood Diabetes crystallized. The primary goal, and the initial aim of the DIAMOND study, is surveillance of incidence through the use of population-based registries. POPULATION-BASED RESEARCH WITH IDDM REGISTRIES With the advent of standardized registries, it became evident that the registries could be used not only for the surveillance of IDDM incidence but also for the surveillance of IDDM mortality. During the 1970s and early 1980s, the initial mortality articles specifically evaluating childhood diabetes began to appear (15-21). Although the studies were limited, there was little question that people who developed IDDM were at an extraordinarily increased risk of dying. Beyond this fact, little was known. As part of the DERI group's efforts, it was recognized that registries established for surveillance could also be readily used to monitor the mortality associated with IDDM. The first multinational population-based study of IDDM mortality was established in 1985, the results of which are now becoming available. Mortality was examined in >9000 cases from four population-based cohorts in Japan, Israel, Finland, and Allegheny County, Pennsylvania (22,23). As in the previous studies, the overall risk of dying for IDDM subjects was found to be much greater than for the general population. Of particular concern was that there was a large cross-population heterogeneity in risk of death, with a greater than threefold difference in the risk of dying depending on country of residence. The scope of the geographic variation of mortality rates has recently become even more evident based on new data from Africa. In highly developed countries, such as those participating in the DERI mortality study, mortality among IDDM subjects was
WHO Multinational Project for Childhood Diabetes
Insulin-dependent diabetes mellitus (IDDM) is one of the most important chronic diseases of children worldwide. IDDM leads to an 8- to 10-fold excess risk of mortality in developed countries, whereas in developing countries, most cases die within a few years. A 60-fold international gradient in IDDM incidence has been reported, and epidemic periods have been identified. A new World Health Organization program, Multinational Project for Childhood Diabetes (Diabetes Mondiale or DIAMOND), has been developed to investigate and characterize global incidence, mortality, and health care. Over 10 yr (1990-1999), this study will collect population-based data concerning IDDM in >90 centers in 50 countries worldwide. The goals of DIAMOND are to collect standard information on incidence, risk factors, and mortality associated with IDDM; evaluate the efficiency and effectiveness of health care and the economics of diabetes; and establish national and international training programs in diabetes epidemiology. It is hoped that the DIAMOND project will be instrumental for the prevention of this serious disease and its sequelae. Diabetes Care 13:1062-68,1990
nsulin-dependent diabetes mellitus (IDDM) is one of the most important chronic diseases of children worldwide (1). In industrialized countries, it is among the most prevalent chronic childhood diseases. Although effective treatment is available, the burden to individuals and society is still high. Annual
I
This article was prepared for the WHO DIAMOND Project Group by Ronald E. LaPorte, laakko Tuomilehto, and Hilary King. Address correspondence and reprint requests to Ronald E. LaPorte, PhD, Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15213. Received for publication 5 February 1990 and accepted in revised form 10 April 1990.
1062
WHO DIAMOND Project Group
IDDM-related costs per diabetic individual in the United States approached $1000 in 1985, an expense well beyond the affordability of individuals or health-care systems in developing countries (2). IDDM often progresses to devastating life-threatening sequelae, e.g., amputation, blindness, and nephropathy. In developed countries, individuals with IDDM have an 8-10 times higher risk of dying prematurely than the nonaffected population (3). In developing countries, most IDDM patients die within a few years after diagnosis (4). It appears that IDDM incidence may be rising in many areas throughout the world (5), thus increasing the major health-care and economic burdens to society. There are considerable gaps in knowledge regarding the global patterns of the disease, host susceptibility, environmental risk factors, related morbidity and mortality, and health care and health economics of IDDM. The lack of information and standards for interpreting existing data impair the ability of the medical community to understand the impact of the disease. Moreover, effective public health measures cannot be developed without adequate data for their evaluation. Therefore, global efforts designed to understand this disease are critically needed. Because of the limited available information, a World Health Organization (WHO) Multinational Project for Childhood Diabetes (Diabetes Mondiale or DIAMOND) has been started. The objectives of this effort are to monitor the international patterns of IDDM incidence to the year 2000, provide a uniform basis for standardized studies of risk factors for IDDM, assess the mortality associated with the disease, evaluate health care (e.g., insulin availability) and health economics associated with diabetes, and develop training programs in diabetes research. This study presents a description of the goals of this project and its evolution.
DIABETES CARE, VOL. 13, NO. 10, OCTOBER 1990
WHO DIAMOND PROJECT GROUP
BACKGROUND The primary goal of the DIAMOND project is the collection of accurate population-based data concerning childhood diabetes worldwide. The accomplishment of this goal is dependent on a close cooperation among the participating centers and a standardized approach for data collection, reporting, and analysis. The evolution of the DIAMOND project began in the late 1970s with the establishment of the first multinational study of macrovascular disease associated with diabetes coordinated from the WHO (6). Considerable information has been gained from that study by examining the relationship of diabetes to heart disease. Of importance for the DIAMOND project was the demonstration that standardized data could be collected from many centers over an extended period of time. Based on this vanguard effort, it was clear that international epidemiological studies in diabetes were indeed feasible and very informative. In the early 1980s, interest in the epidemiology of IDDM began to flourish as the result of the recognition that the place where a child lives is one of the most important determinants of risk of diabetes (7). Moreover, there were indications of epidemic patterns of the disease (8) and a suggestion of a north-south gradient (9). These exciting within- and between-country comparisons pointed out the importance of cross-cultural studies and hence the need for standardization.
EVOLUTION OF INTERNATIONAL IDDM REGISTRY RESEARCH In 1983, a seminal meeting specific to IDDM epidemiology, sponsored by the Juvenile Diabetes Foundation, was held in Philadelphia. The participating scientists discussed the importance of establishing standardized registries to investigate the geographic and secular trends of IDDM. As a result of that meeting, standard criteria for IDDM registries were established, and an approach for international collaboration was adopted, leading to the birth of the Diabetes Epidemiology Research International (DERI) group (10). Also, it was recommended that more population-based registries be established. The DERI group represented a team of investigators who decided to collaborate to conduct standardized cross-cultural studies of IDDM that used population-based registries. At the 1985 International Diabetes Federation meeting in Madrid, a half-day session specifically related to IDDM registries was held. This was the first time that diabetes registries were formally discussed as part of an international congress. The participation of >50 scientists demonstrated the rapidly growing interest. Many of the participants went forward to establish registries in their own countries (11). The head of the WHO Division
DIABETES CARE, VOL. 13, NO. 10, OCTOBER 1990
of Noncommunicable Diseases was present at this meeting. Around this time, a link between pediatric endocrinologists and epidemiologists was formed. There was already an existing collaboration of the endocrinologists as part of the International Study Group on Diabetes. The pediatric endocrinologists and epidemiologists began discussing areas in which they could interface, and a strong liaison has been forged with a primary focus on registries. This has proved to be extremely beneficial for both groups, with the clinical input provided by the endocrinologists and the epidemiological design input provided by the epidemiologists. In 1986, at the International Symposium on the Epidemiology of Diabetes Mellitus, held in Bangkok, Thailand, a session focused on IDDM registries in Asia. More than 100 people were present, and WHO was officially represented. The Bangkok meeting proved to be very beneficial; scientists who were establishing IDDM registries shared their experiences, and others were inspired to develop studies in their countries. The report of the meeting was published in the Bulletin of the World Health Organization (12). Since the mid-1980s, there has been an exponential increase in the number of IDDM registries. As this occurred, it was evident that a central clearinghouse was needed to help foster collaboration and coordination of registry data. Therefore, in 1987, a WHO Collaborating Center for Diabetes Registries and Training was designated at the University of Pittsburgh. The mission of the center was to aid in the development and standardization of diabetes registries. The initial activity of the WHO center was to contact all researchers with existing IDDM registries. The. response from scientists with comparable incidence registries was remarkable, because all were willing to share their data for comparison purposes and agreed to be a part of the DERI group. A standardized reporting scheme was established for global surveillance, with aggregate data sent to the WHO Collaborating Center. This initial effort demonstrated that global surveillance was indeed feasible (13,14). The results of this collaboration underscored the importance of evaluating the reasons for the 60-fold difference in incidence across various countries. Moreover, some of the findings raised the alarming possibility of a global increase in IDDM incidence, in some cases of epidemic proportions (5,8). In 1988, the European Economic Community launched a study called EURODIAB. A portion of the program was designed to map the variation of IDDM in Europe, especially to investigate the observed northsouth incidence gradient. The EURODIAB study differed from the DERI group effort in that cases were enrolled prospectively, the data sent to the coordinating center consisted of individual records, and many of the registries concurrently collected blood samples. This represented a more extensive effort than that in the DERI group studies. This approach is most applicable in countries with advanced health-care systems. The initial
1063
CHILDHOOD DIABETES
funding for the effort will continue through mid-1991. Despite the structural differences between the DERI group and EURODIAB, both efforts use compatible definitions.of IDDM cases and defined population denominators. Therefore, the descriptive epidemiology from the two programs is directly comparable for the commonly collected variables and the common time period. Based on the rapid proliferation of standardized registries, evidence for extraordinary geographic differences in risk, and the evidence of a global increase in the incidence of this serious condition, plans for the establishment of the WHO Multinational Project for Childhood Diabetes crystallized. The primary goal, and the initial aim of the DIAMOND study, is surveillance of incidence through the use of population-based registries. POPULATION-BASED RESEARCH WITH IDDM REGISTRIES With the advent of standardized registries, it became evident that the registries could be used not only for the surveillance of IDDM incidence but also for the surveillance of IDDM mortality. During the 1970s and early 1980s, the initial mortality articles specifically evaluating childhood diabetes began to appear (15-21). Although the studies were limited, there was little question that people who developed IDDM were at an extraordinarily increased risk of dying. Beyond this fact, little was known. As part of the DERI group's efforts, it was recognized that registries established for surveillance could also be readily used to monitor the mortality associated with IDDM. The first multinational population-based study of IDDM mortality was established in 1985, the results of which are now becoming available. Mortality was examined in >9000 cases from four population-based cohorts in Japan, Israel, Finland, and Allegheny County, Pennsylvania (22,23). As in the previous studies, the overall risk of dying for IDDM subjects was found to be much greater than for the general population. Of particular concern was that there was a large cross-population heterogeneity in risk of death, with a greater than threefold difference in the risk of dying depending on country of residence. The scope of the geographic variation of mortality rates has recently become even more evident based on new data from Africa. In highly developed countries, such as those participating in the DERI mortality study, mortality among IDDM subjects was
