The Emerging Global Epidemic of Type 1 Diabetes

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Abstract
Type 1 diabetes mellitus (T1D) can occur at any age, with a peak in incidence around puberty. Classification between T1D and type 2 diabetes becomes more challenging with increasing age of onset of T1D over time develops in genetically predisposed individuals. The main susceptibility is conferred with human leukocyte antigen (HLA) genes. Some of the geographic variation in incidence and familial aggregation is explained by differences in HLA haplotypes. In many populations, the incidence is somewhat higher in males than in females, and a 1.3- to 2.0-fold male excess in incidence after about 15 years of age exists in most populations. The incidence of childhood-onset T1D varies markedly among countries. East Asian and native American populations have low incidences (approximately 0.1–8 per 100 000/year), while the highest rates are found in Finland (>60 per 100 000/year), Sardinia (40 per 100 000/year), and Sweden (47 per 100 000/year). The risk is highest in European-derived populations. About 10 %–20 % of newly diagnosed childhood cases of T1D have an affected first-degree relative. Those with an affected sibling or parent have a cumulative risk of 3 %–7 % up to about 20 years of age, as compared with <1 % in the general population. The cumulative incidence among the monozygotic co-twins of persons with T1D is less than 50 %. Thus, the majority of genetically predisposed people do not develop T1D. Studies assessing temporal trends have shown that the incidence of childhood-onset T1D has increased in all parts of the world. The average relative increase is 3 %–4 % per calendar year. For instance, in Finland, the incidence today is 5 times higher than 60 years ago. At the same time, the age at onset of T1D in children has become younger. It is strongly believed that nongenetic factors are important for the development of T1D and its increase, but the causative evidence is missing. The causes for this increasing trend and current epidemic still remain unknown.