The multiple origins of Type 1 diabetes

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43 Citations (Scopus)

Abstract

It is widely accepted that Type 1 diabetes is a complex disease. Genetic predisposition and environmental factors favour the triggering of autoimmune responses against pancreatic β-cells, eventually leading to β-cell destruction. Over 40 susceptibility loci have been identified, many now mapped to known genes, largely supporting a dominant role for an immune-mediated pathogenesis. This role is also supported by the identification of several islet autoantigens and antigen-specific responses in patients with recent onset diabetes and subjects with pre-diabetes. Increasing evidence suggests certain viruses as a common environmental factor, together with diet and the gut microbiome. Inflammation and insulin resistance are emerging as additional cofactors, which might be interrelated with environmental factors. The heterogeneity of disease progression and clinical manifestations is likely a reflection of this multifactorial pathogenesis. So far, clinical trials have been mostly ineffective in delaying progression to overt diabetes in relatives at increased risk, or in reducing further loss of insulin secretion in patients with new-onset diabetes. This limited success may reflect, in part, our incomplete understanding of key pathogenic mechanisms, the lack of truly robust biomarkers of both disease activity and β-cell destruction, and the inability to assess the relative contributions of various pathogenic mechanisms at various time points during the course of the natural history of Type 1 diabetes. Emerging data and a re-evaluation of histopathological, immunological and metabolic findings suggest the hypothesis that unknown mechanisms of β-cell dysfunction may be present at diagnosis, and may contribute to the development of hyperglycaemia and clinical symptoms.

Original languageEnglish
Pages (from-to)135-146
Number of pages12
JournalDiabetic Medicine
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2013

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Autoantigens
Genetic Predisposition to Disease
Natural History
Autoimmunity
Hyperglycemia
Disease Progression
Insulin Resistance
Biomarkers
Clinical Trials
Insulin
Diet
Viruses
Inflammation
Antigens
Genes
Gastrointestinal Microbiome

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

The multiple origins of Type 1 diabetes. / Pugliese, Alberto.

In: Diabetic Medicine, Vol. 30, No. 2, 01.02.2013, p. 135-146.

Research output: Contribution to journalArticle

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