Both type I and type II diabetes (T1D and T2D) are associated with diverse metabolic processes that stem from hyperglycemia due to deficient secretion or action of insulin rendering patients at risk for secondary renal, vascular, neurological and ophthalmologic complications. Those affecting the brain and optic nerve are of particular importance because they may lead to permanent and disabling deficits that affect normal nervous system functioning. T1D usually develops before age 30 years, and such individuals typically need insulin injections for the rest of their life. Their disease is caused by the gradual loss of insulin producing β-cells in the pancreas. Patients with T2D are typically older, often obese, and at high risk for hypercholesterolemia and heart disease, with relative insulin resistance that perpetuates hyperglycemia. 

The epidemiology of diabetes is well known. In the United States alone. More than one million people are living with the more severe type, T1D, with approximately 80 people per day or 30,000 individuals per year, newly diagnosed. The global incidence of T1D is increasing at a rate of approximately 3% to 4% per year, notably among younger children. These statistics highlight the need for both better TID therapy and the continued push towards its prevention. 

In the past several years, at least nine lines of investigations suggest the importance of genetic, environmental, infectious and inflammatory mechanisms in the causation of T1D.  
1.    T1D appears to be caused by autoimmune mechanisms directed against the insulin-producing β-cells with up to 90% of T1D patients harboring or more autoantibodies. 
2.    The pancreas of all newly diagnosed T1D patients show inflammation in the region of β-cells. 
3.    The autopsies of two children who died prematurely with T1D showed pancreatic islet cell membrane-bound, superantigens indicating integrated bacterial or viral genes. 
4.    The genetic risk of T1D is strongly linked to HLA class II DR3 and DR4 haplotypes, with the highest risk in those with the DR3/DR4 genotype. 
5.    T1D occurs with increased frequency in association with several other autoimmune disorders, including Grave disease, pernicious anemia, Hashimoto thyroiditis, myasthenia gravis, anti-phospholipid antibody syndrome, and Addison disease. 
6.    Animal and human models of T1D implicate T-cells autoimmunity in β-cell destruction based upon a mechanism of molecular mimicry in which an infectious antigen prime autoreactive T-cells to recognize peptides common to both microbial antigens and β-islet cells. 
7.    The gut microbiome which is both less diverse and protective in normal individuals, is hypothesized to be perturbed in early development, predisposing to T1D by modulating innate immunity or altering intestinal permeability.  
8.    Viruses, with their potential to induce innate and adaptive immune responses and local inflammation in the pancreas and other organs, have been suspected of initiating this autoimmune process. The etiologic link between T1D and viruses is based on epidemiological, serological, and histological findings, as well as experimental in vivo and in vitro studies. Some  microbial and host proteins with sequence or structural homology may go unrecognized as self-proteins stimulating immune response against the viral antigen which becomes cross-reactive against the homologous sequence of the host β-cell proteins by the mechanism of molecular mimicry.  
9.    One other possible mechanism of infection-induced autoimmunity of insulin producing β-cells in the pancreas occurs through bystander activation, whereby the infection of neighboring β-cells stimulates local inflammation with the appearance of T-cells and other inflammatory cells that release inflammatory proteins that lead to killing of β-cells. 

Insulin replacement has been the primary treatment of all forms of diabetes for almost a century, but inadequate control of its delivery has allowed a number of complications to markedly diminish the quality of life of affected individuals. The recognition that a subset of patients present an autoimmune form of T1D is now well accepted and has led to different approaches to therapy.  The spontaneous but temporary remission after onset of T1D, known as the honeymoon period, reflecting reduced stress on residual β-cells after initial insulin treatment, appears to be the window of opportunity to exploit the use of intervention therapy to block the autoimmune response, early in the course of the disease before appearance of hyperglycemia, and while there are sufficient β cells remaining.  A variety of biomarkers including HLA haplotypes, and circulating autoantibodies to β-cell antigens insulin, GAD65, IA‐2, ZnT8, and IGRP, may be useful in selecting individuals for targeted experimental therapy, to evaluate the risk and rate of disease progression of T1D to overt hyperglycemia.