Fetal Determinants of Type 2 Diabetes

Author(s): Brigitte Reusens, Susan E. Ozanne, Claude Remacle.

Journal Name: Current Drug Targets

Volume 8 , Issue 8 , 2007

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Abstract:

Type 2 diabetes, which has dramatically increased during the last decade normally results from a combination of pancreatic beta cell dysfunction and insulin resistance. One of the most recent risk factors identified for type 2 diabetes is a sub-optimal fetal and neonatal environment. Numerous human epidemiological studies worldwide have highlighted that a disturbed nutritional environment of the fetus, either poor or too abundant will compromise the health of the offspring by increasing the susceptibility to insulin resistance, to glucose intolerance and to diabetes in later life. In addition to adverse intrauterine events, the detrimental role of catch-up growth and of the mismatch between the prenatal and the postnatal metabolic environment in such pathology is now clear. To understand the mechanisms that are responsible for such programming and to be able to design prevention strategies, a number of animal models have been created. This manuscript reviews the data from several rodent models in which maternal or neonatal diet has been altered. These include models of maternal under-nutrition and over-nutrition as well as gestational diabetes. In general, abnormal beta cell mass and beta cell dysfunction are present at birth and insulin resistance, glucose intolerance and diabetes appear in adult offspring. Obesity, pregnancy and ageing exaggerate the phenotype and there is some evidence to suggest that the phenotype can be transmitted to a second generation independently of any further environmental modification. Possible underlying mechanisms are discussed and evidence for potential early intervention strategies are reported.

Keywords: Programming, beta-cell development, insulin secretion, insulin resistance, glucose intolerance, rat

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Article Details

VOLUME: 8
ISSUE: 8
Year: 2007
Page: [935 - 941]
Pages: 7
DOI: 10.2174/138945007781386866
Price: $58

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