Type 1 diabetes (T1DM) is one of the most prevalent severe chronic diseases of childhood, affecting more than 170,000 children in the United States, an increase of 23% since 2001 . In the US, more than 25,000 children are diagnosed annually with 1:200 children and 1:100 adults diagnosed with T1DM during the lifespan . T1DM is the leading cause of end-stage renal disease, blindness, and amputation, and a major cause of cardiovascular disease and premature death in the general population. Annually, in the US, an estimated 70–200 children die at the onset of diabetes  with 30% of children who develop diabetes presenting with ketoacidosis. For unknown reasons, the incidence of T1DM has been increasing progressively over the last half century by 3–5% per year . In addition the percentage of children expressing the highest risk HLA genotype (DR3/4-DQ2/8) has dramatically decreased over the past 50 years , apparently reflecting increased disease penetrance of lower risk haplotypes. The high incidence, associated severe morbidity, mortality, and associated healthcare expenditures make T1DM a prime target for prevention. Population-based epidemiological studies as well as family studies and clinical trials have provided new insights into the pathogenesis and natural history of T1DM. Such studies are essential for appropriate diagnosis and for evidence-based programs of prevention and treatment.
Prevalence and incidence
The prevalence of T1DM, that is the proportion of people in the population who have the disease at a given point in time, is determined not only by disease incidence but also by case survival, which may vary markedly in populations. The prevalence of β-cell autoimmunity appears to be roughly proportional to the incidence of T1DM in different populations. In contrast, the prevalence of β-cell autoimmunity in first-degree relatives of T1DM persons does not differ a lot between high and low risk countries for T1DM.The prevalence of T1DM in children aged less than 15 years ranges from 0.05 to 0.3% in most European and North American populations .
Incidence is the rate at which new cases of disease appear in the population and is usually expressed as the annual number of new cases per 100,000 persons. Incidence of T1DM varies by geographic location, ethnicity, age, gender, and time. The incidence of T1DM is increasing worldwide both in lowand high incidence populations (Figure 2.1) . The average annual incidence is the highest in Finland where it has increased to 64 per 100,000 per year in 2005  while the current mean incidence is 18/100,000 person-years in Australia .
One of the most striking characteristics of T1DM is the large geographic variability in the incidence [10–13]. The incidence rates of T1DM vary from 0.73/100,000 per year in China  to 60/100,000 per year in Finland. A child in Finland is 100 times more likely to develop diabetes than a child in China. A clear difference appears between the Northern and Southern Hemisphere with countries below the equator having a lower incidence; in contrast above the equator the disease is common. The largest intracontinental variation in incidence appears to be in Europe. There are also noticeable within-country variations in incidence rates, which can only be partially explained by racial composition of the population.
The geographic and ethnic variation in T1DM risk may reflect either different pools of susceptibility genes or different prevalence of causative environmental factors or a combination of both.
Race and ethnicity
There are also striking racial differences in T1DM risk within the same population, although they are not as important as the geographic differences. In the United States, non-Hispanic whites are about one and a half times as likely to develop T1DM as African Americans or Hispanics [15,16]. There are similar differences reported in Europe, where France has lower rates than do Britain and Scandinavia.
Interestingly, there is also evidence that migrants from a country with low incidence of T1DM soon have the higher rate incidence of the country where they live; for example South Asian children living in the UK have similar overall rates of T1DM compared to indigenous white children . Genetic factors are unlikely to explain such a rapid change, implying an influence of environmental factors in disease etiology.
Age and gender
T1DM incidence peaks at the ages of 2, 4–6 and 10–14 years, perhaps due to alterations in the pattern of infections or increases in insulin resistance. Few cases of T1DM develop in the first year of life. The main incidence peak occurs at puberty, with females having a pubertal peak about 1 year earlier. There is a decrease in incidence after puberty for both sexes . In Sweden, the age-specific incidence rates vary from 5–20/100,000 person-years in adults aged 15–35 years and decline with age. Several studies indicate a stable or decreasing trend of T1DM among young adults , while, in contrast, a study from Italy (lower-risk population) found that the incidence from 1984 to 1996 increased not only in children but also in young adults .
In general, males and females have similar risk of T1DM. In lower-risk populations, such as Japan or African Americans, there is a female preponderance,while in high-risk groups, there is a slight male excess . Interestingly, even within Europe, populations with an incidence higher than 20/100,000 (Sardinia, UK, Italy, Finland,Norway) had male excess, whereas those with a lower rate (the Baltic countries,Macedonia, Yugoslavia, Romania) had female excess .
Increasing incidence and seasonality
There is evidence for marked variations in the incidence of T1DM over time, both seasonally and annually. In the Northern Hemisphere, the incidence declines during the warm summer months; similarly in the Southern Hemisphere, the seasonal pattern exhibits a decline during the warm months of December and January, implicating a climatic factor. This seasonal pattern appears to occur predominantly in older children , suggesting that factors triggering diabetes may be related to school attendance. Most population-based registries have shown increasing T1DM incidence over time [22,23]. Several studies have observed periodic outbreaks superimposed on a steady secular increase in incidence.
While the increase in T1DM incidence has affected all age groups, several studies have reported a particular increase among the youngest children . In the youngest age group (0–4 years) an increase of 11% and 24% per year was reported in, respectively, the UK and Switzerland . On the contrary, some studies show the highest increase in incidence in children 10–14 years old .
In the EURODIAB ACE Study Group, representing most European countries and Israel, the rates of increase were 6.3% (4.1–8.5%) for children aged 0–4 years, 3.1% (1.5–4.8%) for 5–9 years, and 2.4% (1.0–3.8%) for 10–14 years .