Developmental origins of diabetes: The role of oxidative stress.

The 'thrifty phenotype' hypothesis proposes that the fetus adapts to an adverse intrauterine milieu by optimizing the use of a reduced nutrient supply to ensure survival, but by favoring the development of certain organs over that of others, this leads to persistent alterations in the growth and function of developing tissues. This concept has been somewhat controversial, however recent epidemiological, clinical, and animal studies provide support for the developmental origins of disease hypothesis. Underlying mechanisms include reprogramming of the hypothalamic-pituitary-adrenal axis, islet development, and insulin signaling pathways. Emerging data suggests that oxidative stress and mitochondrial dysfunction may also play a critical role in the pathogenesis of type 2 diabetes in individuals who were growth retarded at birth.