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Published on: May 6, 2013
Developmental aspects in the pathogenesis of type 2 diabetes
1Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Box 116, Cambridge CB2 2QQ, UK.
Molecular and Cellular Endocrinology
|December 12, 2001
Summary
Low birthweight increases type 2 diabetes risk due to fetal adaptations. Certain gene variants may protect early survival but raise long-term disease risk, impacting adulthood health.
Area of Science:
- Developmental biology
- Metabolic disorders
- Genetics
Background:
- Low birthweight is a known risk factor for adult-onset type 2 diabetes.
- Fetal adaptive responses to undernutrition may mediate this increased risk.
- Specific genetic factors, including gene copy number variations and imprinted genes, are implicated in fetal growth and long-term metabolic health.
Purpose of the Study:
- To explore the role of fetal adaptive mechanisms and genetic factors in the link between birthweight and type 2 diabetes risk.
- To investigate how 'thrifty genotypes' influence survival and subsequent disease susceptibility.
- To examine the potential influence of paternally and maternally inherited genetic factors on fetal growth and adult metabolic outcomes.
Main Methods:
- Review of existing literature on fetal programming, genetics, and type 2 diabetes.
- Analysis of proposed genetic mechanisms, including insulin gene variable number of tandem repeats (VNTR) and imprinted genes like IGF2R.
- Consideration of evolutionary perspectives on survival adaptations and their long-term health consequences.
Main Results:
- Fetal adaptive metabolic/endocrine mechanisms during undernutrition may increase type 2 diabetes risk.
- Insulin gene VNTR class III/III genotype, potentially paternally inherited, is linked to larger birth size and adult type 2 diabetes.
- Maternally inherited factors (mitochondrial DNA, IGF2R) may restrain fetal growth, potentially protecting maternal survival.
Conclusions:
- Genetic factors influencing fetal growth and adaptation play a crucial role in determining long-term type 2 diabetes risk.
- The 'thrifty genotype' hypothesis provides a framework for understanding how adaptations for survival can lead to metabolic disease.
- Both early life environment and inherited genetic predispositions interact to shape adult metabolic health outcomes.
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