Predictive, preventive and personalized medicine (PPPM) as a strategic avenue and global tool for advancing T1D-related care: Fundamental, Applied and Affiliated Issues

Autor: Olga Golubnitschaja, Mihail A Paltsev, Trevor G. Marshall, Harry W. Schroeder, Matt von Herrath, Martin Frank, Paolo Pozzilli, Ashot Mkrtumyan, Sergey V. Suchkov
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: The EPMA Journal
ISSN: 1878-5085
1878-5077
Popis: Type one diabetes (T1D: (juvenile onset) whilst being a chronic disease, the defining feature of which is the destruction of the insulin-secreting beta-cells and subsequent dependence on exogenous insulin, is possessing with hallmark characteristics of the complex T cellmediated autoimmunity superimposed on genetic susceptibility. Both genetic and environmental factors combine to precipitate disease, and the outcome of the pathological process is dependent on multiple interrelated factors. The annual global incidence of T1D is increasing by 3-5% per year. Both HLA-genes and immune markers (autoantibodies/autoAbs) have been validated as predictive biomarkers of the subsequent development of the disease in higher-risk relatives and the lower-risk general population. Over the last three decades, using a combination of genomic, proteomic, and metabolomic biomarkers, clinicians are now able to quantify an individual’s disease risk from 1 in 100,000 to more than 1 in 2. The HLA genes are reported to account for approximately 40-50% of the familial aggregation of T1D. Current approaches for the prediction of T1D in screening studies take advantage of genotyping HLA-DR and HLA-DQ loci, which is then combined with family history and screening for autoAbs directed against isletcell Ags. Inclusion of additional moderate HLA risk haplotypes may help identify the majority of children withT1D before the onset of the disease. Fine mapping and functional studies are gradually revealing the complex mechanisms whereby immune self-tolerance is lost, involving adaptive immunity. Genetic prediction of T1D risks is showing promise of use for preventive strategies. And understanding of the genetics, environmental factors, and natural history of T1D has resulted in greater understanding of the etiology and epidemiology of the disease. The clinical care of patients with T1D has greatly improved over the past few decades; however, it remains impossible to completely normalize blood sugar utilizing currently available tools. Meanwhile, subclinical and predictive diagnostic armamentarium is still far from being unique, and innovative algorithms that significantly differ from the clinical approaches should become the major bricks to be laid into the basis of a subclinical diagnosis of pre-T1D. Generally, there are three levels desirable for an optimal pre-T1D and T1D-related healthcare, namely, (i) 1 level: prediction of the familial predisposition, targeted prevention of pre-T1D early in childhood; (ii) 2 level: prediction of early/premature aging and targeted prevention of T1D-related pre-stages; (iii) 3 level: prediction of secondary complications in the cohort of T1D-patients and creation of personalized treatment modes tailored to the patient to prevent postT1D complications frequently developed. Accurate prediction is vital for T1D prevention so that preventive treatment can be given to those individuals who are most likely to develop the disease. Predictive medicine is intended more so for healthy individuals, its purpose being to determine whether susceptibility to a * Correspondence: ssuchkov57@gmail.com I.M.Sechenov First Moscow State Medical University, Moscow, Russia Full list of author information is available at the end of the article Suchkov et al. EPMA Journal 2014, 5(Suppl 1):A69 http://www.epmajournal.com/content/5/S1/A69
Databáze: OpenAIRE
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