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Age-Dependent Influences on the Origins of Autoimmune Diabetes

Evidence and Implications

From the Institute of Cell and Molecular Science, Queen Mary College, University of London, London, U.K

The first 300 words of the full text of this article appear below.

A decade ago we proposed that environmental factors operating in early life lead to type 1 diabetes, outlining the evidence and the implications if the hypothesis was true (1). Today we can be confident that environmental factors can indeed operate in childhood to cause type 1 diabetes, but we now review evidence that this is unlikely to be true in the generality of cases of type 1 diabetes. Indeed, type 1 diabetes presenting in adult life is remarkably distinct from diabetes presenting in children in terms of its genetic, immune, metabolic, and clinical features. If the mechanism and timing of disease induction is also distinct in adult-onset, compared with childhood-onset, type 1 diabetes, then these differences would have implications for our understanding of the disease pathogenesis, prediction, and prevention. The aim of this article is to explore the different influences of genetic and nongenetic factors on type 1 diabetes according to the age of clinical disease onset and the potential consequences of such differences.

Type 1 diabetes is caused by the destruction of insulin-secreting islet cells by an immune-mediated process. This adverse immune response is induced and promoted by the interaction of genetic and environmental factors and is one of a group of autoimmune diseases that affect 10% of the population in the developed world (2–5).

	AGE-DEPENDENT ROLE FOR GENETIC FACTORS

 
Type 1 diabetes is genetically determined as shown by family, twin, and genetic studies. The frequency of type 1 diabetes is higher in siblings of diabetic patients (e.g., 6% by age 30 years in the U.K.) than in the general population (0.4% by age 30 years) (6). Familial clustering could be caused by shared genetic or environmental factors, and to distinguish between them, twin studies have been used. Higher concordance rates for autoimmune diseases in identical . . . [Full Text of this Article]

	AGE-DEPENDENT ROLE FOR NONGENETIC FACTORS

 

	DISEASE INDUCTION BY ENVIRONMENTAL FACTORS

 
Maternal-related events influence diabetes risk.
Exposure to viruses.
Nature of weaning diet.

	ACTIVATION OF THE DIABETES-ASSOCIATED IMMUNE RESPONSE

 

	DESTRUCTION BY THE DIABETES-ASSOCIATED IMMUNE RESPONSE

 
Variable rate of disease progression.
Genetic factors affect disease rate.

	IMPLICATIONS FOR DISEASE PATHOGENESIS

 
Age-dependent variation in disease progression.
Age-dependent variation in growth.
Age-dependent variation in disease outcome.

	IMPLICATIONS FOR PREDICTION

 

	IMPLICATIONS FOR PREVENTION

 
Address correspondence and reprint requests to Prof. David Leslie, Department of Diabetes, St. Bartholomews Hospital, West Smithfield, London EC1A 7BE, U.K. E-mail: r.d.g.leslie@mds.qmw.ac.uk

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