Type 1 diabetes: A predictable disease

Abstract

Type 1 diabetes (T1D) is an autoimmune disease characterized by loss of insulin producing beta cells and reliance on exogenous insulin for survival. T1D is one of the most common chronic diseases in childhood and the incidence is increasing, especially in children less than 5 years of age. In individuals with a genetic predisposition, an unidentified trigger initiates an abnormal immune response and the development of islet autoantibodies directed against proteins in insulin producing beta cells. There are currently four biochemical islet autoantibodies measured in the serum directed against insulin, glutamic decarboxylase, islet antigen 2, and zinc transporter 8. Development of islet autoantibodies occurs before clinical diagnosis of T1D, making T1D a predictable disease in an individual with 2 or more autoantibodies. Screening for islet autoantibodies is still predominantly done through research studies, but efforts are underway to screen the general population. The benefits of screening for islet autoantibodies include decreasing the incidence of diabetic ketoacidosis that can be life threatening, initiating insulin therapy sooner in the disease process, and evaluating safe and specific therapies in large randomized clinical intervention trials to delay or prevent progression to diabetes onset.

Immunological GABAergic interactions and therapeutic applications in autoimmune diseases

“…Despite many encouraging preclinical studies, the clinical benefits of antigen therapy in T1D have been limited, and much below expectations. It is beyond the scope of this manuscript to discuss these studies in detail, but they have been recently reviewed [76,92,98].…”

“…Antigens, or related peptides, have been administered by a variety of routes (subcutaneous, oral or nasal) and adjuvant formulations [76,[91][92][93][94][95][96][97][98]. Genetic (DNA) vaccination has also been investigated [99][100][101][102].…”

Autoimmunity in narcolepsy

“…In general, autoimmune diseases are characterized by specific auto-antibodies [44, 45]. However, the search for characteristic narcolepsy autoantibodies has been futile with no auto-antibodies consistently found [46–60].…”

Diabetes mellitus in childhood: an emerging condition in the 21st century

“…In children, IAA is often the first antibody to develop, while adults tend to have higher rates of GADA upon diagnosis. 53 Through the analysis of data collected by prospective studies on the natural history of DM1 in first-degree relatives of high-risk patients with HLA haplotypes monitored from birth, it was observed that the detection of multiple autoantibodies against the islet in these children could be interpreted as a pre-clinical stage of DM1. In addition, observation within a period of 10 years after seroconversion suggests that the lower the age upon the onset of autoimmunity directed at the islet, the quicker the progression to clinical diabetes before puberty, and that the processes responsible for this phenomenon must be operating before the age of 2 years, or even during pregnancy.…”