Both primary and secondary prevention efforts in T1D are reviewed below. Primary Prevention Primary prevention trials have been conducted in high-risk individuals who have no islet autoantibodies or metabolic abnormalities. autoimmune disorders including rheumatoid arthritis. strong class=”kwd-title” Keywords: Type 1 Diabetes, Autoimmunity, Autoantibodies, Prevention, Immune therapies Introduction Type 1 diabetes mellitus (T1D), the immune mediated form of diabetes requiring insulin treatment, is usually a prevalent chronic autoimmune disease affecting both children and adults. 1C3 The incidence of T1D is usually increasing dramatically, doubling in the last 20 years. The vast majority of T1D cases result from autoimmune mediated, non-reversible destruction of insulin producing beta cells within the pancreatic islets. Progressive beta cell destruction and decreased endogenous insulin production occur during a silent preclinical phase in which blood glucose levels remain normal. During the preclinical phase of disease, autoantibodies directed toward beta cell specific antigens can be measured in a patients blood, and measurement of islet autoantibodies has made T1D a predictable disease. Inflammation and T cell mediated destruction of islet beta cells result in the development of clinically apparent disease marked by abnormal glucose homeostasis. With the ability to assess diabetes risk and predict disease onset, many large clinical trials aimed at disease prevention have been completed over the last decade. These studies have not completely prevented disease onset but hold promise for identifying an intervention to slow disease progression. This review focuses on the natural history of T1D, brief sections on clinical diagnosis and treatment, prevention efforts in preclinical T1D, and a final section applying the lessons learned from diabetes prevention to rheumatic diseases. Epidemiology Great strides in understanding the natural history and pathogenesis of T1D have occurred in large part from longitudinal studies following children from birth for the development of islet autoantibodies and diabetes development (DAISY in the United States, EURODIAB in Germany, and DIPP in Finland).4C7 T1D incidence has also been well defined through these studies. The incidence of T1D varies greatly by geographical location with an average annual incidence of 2.3% per year. The incidence among Caucasians in the United States is usually 17.8/100,000 patient years for children less than 14 Sitafloxacin years of age. Unlike most other autoimmune diseases in which females are affected more than males, males and females are equally affected with T1D. The age of diabetes onset has two peaks, one in children 5C7 years of age and again in adolescents 10C14 years old.8 Adults also develop T1D with approximately 25% of new T1D cases diagnosed in individuals older than 18 years of age.3 With few exceptions, the incidence rate for T1D is usually rising in all age groups between 2.4C3.3% per year, with the largest increase among children who are less than 5 years old.9 T1D is still the predominant form of diabetes in youth, even though the incidence of type 2 diabetes (T2D) mellitus is increasing. More than 85% of people with T1D or T2D diabetes who are less than 20 years of age have T1D.10 Although the majority of individuals diagnosed with T1D have no family history of T1D, the development is strongly influenced by genetic factors.11 In the general population, there is a 1 in 300 lifetime risk for developing T1D.12 Individuals with a first degree relative with T1D have a 1/7 to 1/30 lifetime risk of Rabbit Polyclonal to SLC39A7 developing the disease depending on the affected relative. Children of mothers with T1D carry a ~3% lifetime risk of developing T1D, while the risk increases to ~5% for a Sitafloxacin father with diabetes.11 A recent analysis of monozygotic twins that were initially discordant for T1D showed that by 60 years of age, persistent autoantibody positivity, T1D, or both had occurred in Sitafloxacin 78% of these individuals.13 Risk Factors Genes T1D is clearly a polygenic disorder as evidenced by genome-wide association studies (GWAS), which has identified more than 40 genetic polymorphisms that confer susceptibility to T1D development.14,15 The human leukocyte antigen (HLA) class II region on chromosome 6 confers 50% of the genetic susceptibility to T1D.12 Specific MHC class II alleles can.
