The Big Diabetes Lie

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Epidemiology is defined as "the study of the distribution and determinants of health-related states and events in populations, and the applications of this study to the control of health problems" (1). Epidemiology is the scientific basis of public health. One might wonder why we should even consider epidemiology for disorders such as type 1 diabetes, as remarkable advances have occurred in basic research during the past few decades. However, epidemiology has proven to be the mainstay of prevention for infectious and chronic diseases in the United States and across the world during the past century. To cite an example, life expectancy has increased by approx 25 yr since 1950 (2). The vast majority of this increase (24 of the 25 yr) has been the result of public health applications of epidemiologic research (3). We believe that the same will hold true for type 1 diabetes.

Epidemiology will continue as the core science for public health during the new millennium, in combination with advances in genetics, immunology, and the environmental sciences. Should it become possible to modify potential etiologic determinants of type 1 diabetes or implement new interventions (e.g., dietary modifications, islet cell transplants, gene therapy, etc.), epidemiologic data based on these and other characteristics will be essential for assessing the efficacy and economic impact of implementing such strategies. A discussion of these issues, which serve as a model for other multifac-torial diseases, forms the basis of this chapter.

From: Contemporary Endocrinology: Type 1 Diabetes: Etiology and Treatment Edited by: M. A. Sperling © Humana Press Inc., Totowa, NJ


A typical first step for studying the epidemiology of any disorder is the evaluation of geographic and temporal variations in disease incidence. These investigations require the development of a standardized epidemiologic approach, for reasons similar to those that justify the utilization of laboratory standards. To compare results among laboratories, one needs to employ comparable and standardized methodologies. Thus, a standardized epidemiologic protocol was developed to permit accurate comparisons of the incidence of type 1 diabetes worldwide. This began in 1983 at an important meeting held in Philadelphia, PA by the Juvenile Diabetes Foundation (4). At that time, the first standardized protocol for the development of incidence registries for type 1 diabetes was outlined. Since then, this protocol has been used by essentially all of the registries for type 1 diabetes in the world and has permitted direct comparisons of standardized data regarding the epidemiology of the disease.

Once a standardized protocol was available, the next step was to establish a philosophy of data sharing. Data sharing is rare among most scientists in diabetes, but it has become the norm among diabetes epidemiologists. These collaborations began with early studies conducted by the Diabetes Epidemiology Research International (DERI) Group. In the mid-1980s, all researchers who had existing data participated in DERI by comparing the epidemiology of type 1 diabetes from their registries. Over 20 registries worldwide participated. This effort resulted in one of the largest global collaborations ever seen in medical research. Although the initial findings were extremely interesting, it became evident by the late 1980s that there were broad gaps in our knowledge about the distribution of type 1 diabetes in children worldwide (5).

By 1990, two international groups working on the epidemiology of type 1 diabetes had been developed. The first was the EURODIAB Project (6), which represented standardized type 1 diabetes incidence registries in Europe. The second was the World Health Organization (WHO) Multinational Project for Childhood Diabetes, also known as Diabetes Mondiale, or the DiaMond Project (7). The DiaMond Project included type 1 diabetes incidence registries from all continents. Because of these two important projects, the descriptive epidemiology of type 1 diabetes has been mapped for most of the world, and we now know more about the international variation in the incidence of type 1 diabetes than practically any other chronic disease. Within a short 15-yr time period, the epidemiology of type 1 diabetes rose from a "black hole" of ignorance to one of the best characterized chronic diseases worldwide because of this remarkable global cooperation. Here, we describe some of these results and their implications for disease prevention.

Geographic Variation in Incidence

The variation in the incidence of type 1 diabetes worldwide is greater than that observed for any other chronic disease in children. Currently, there are incidence data from more than 60 countries around the world. As illustrated by Fig. 1, the global variation in risk is enormous. A child in Helsinki, Finland is almost 400 times more likely to develop diabetes than a child in Sichuan, China (8). To put this in perspective, consider the following example. If children in the United States had the same risk of developing type 1 diabetes as children in China, then instead of 13,000 newly diagnosed children each year, there would be only 56. In other words, over 99% of the annual new cases of type 1 diabetes in the United States would be avoided.

Fig. 1. Type 1 diabetes incidence rates per 100,000/yr worldwide. Note: PRC, People's Republic of China; JPN, Japan; DEN, Denmark; UK, United Kingdom; US, United States; NOR, Norway; SCOT, Scotland; SWD, Sweden; CAN, Canada; FIN, Finland.

Interestingly, the other epidemiologic features of type 1 diabetes are remarkably similar across populations, despite the enormous variation in disease risk (9). Incidence rates among males and females do not differ significantly, and the peak age at onset for both sexes occurs near the time of puberty. Thus, compared to all other risk factors, including human leukocyte antigen (HLA) haplotypes, viral infections, or the presence of autoanti-bodies, the place where a child lives is the most potent determinant of type 1 diabetes risk, excluding genetic/racial differences. If we knew what was causing the geographic patterns of type 1 diabetes, we would be well on our way to preventing the disease.

Not unexpectedly, the epidemiology of type 1 diabetes is the result of both genetic and environmental processes. Most of the low-incidence populations are Asian (i.e., Japanese, Chinese). The genetic characteristics of these groups are somewhat different than those for Caucasians, African-Americans, and Hispanics. Moreover, much is known about the genetic determinants of type 1 diabetes, and these are discussed in the next section. Here, we focus on the evidence for an environmental etiology. Epidemio-logic data, including studies of temporal trends and migrants, provide very strong support for an environmental role in the development of the disease.

Temporal Trends in Incidence

Temporal trends in chronic disease incidence rates are almost certainly environmentally induced. If one observes a 50% increase in the incidence of a disorder over 20 yr, it is most likely the result of changes in the environment because the gene pool cannot change that rapidly. Type 1 diabetes is a very dynamic disease. Throughout Europe, there has been an approx 3% rise in disease incidence since the mid-1960s, making type 1 diabetes an important and very costly disorder (10). In the United States, the temporal trends are less clear, primarily because of the lack of monitoring. The longest ongoing type 1 diabetes registry is from Allegheny County, Pennsylvania, the region surrounding the city of Pittsburgh (11); a rapid increase in disease incidence has been observed since 1965. This trend was most apparent during the 1990s. These results

Fig. 1. Type 1 diabetes incidence rates per 100,000/yr worldwide. Note: PRC, People's Republic of China; JPN, Japan; DEN, Denmark; UK, United Kingdom; US, United States; NOR, Norway; SCOT, Scotland; SWD, Sweden; CAN, Canada; FIN, Finland.

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