Mechanisms Linking Suboptimal Early Nutrition and Increased Risk of Type 2 Diabetes and Obesity, ,

https://doi.org/10.3945/jn.109.111237Get rights and content
Under an Elsevier user license
open archive

Abstract

Epidemiological studies have revealed a relationship between poor early growth and development of type 2 diabetes and other features of metabolic syndrome. The mechanistic basis of this relationship is not known. However, compelling evidence suggests that early environmental factors, including nutrition, play an important role. Studies of individuals in utero during a period of famine showed a direct relationship between maternal nutrition and glucose tolerance. Further evidence has come from studies of monozygotic twins who were discordant for type 2 diabetes. Nutrition during the early postnatal period has also been shown to have long-term consequences on metabolic health. Excess nutrition and accelerated growth during the neonatal period has been suggested to be particularly detrimental. Animal models, including maternal protein restriction, have been developed to elucidate mechanisms linking the early environment and future disease susceptibility. Maternal protein restriction in rats leads to a low birth weight and development of type 2 diabetes in the offspring. This is associated with β cell dysfunction and insulin resistance. The latter is associated with changes in expression of key components of the insulin-signaling cascade in muscle and adipocytes similar to that observed in tissue from young men with a low birth weight. These differences occur prior to development of disease and thus may represent molecular markers of early growth restriction and disease risk. The fundamental mechanisms by which these programmed changes occur remain to be fully defined but are thought to involve epigenetic mechanisms.

Cited by (0)

1

Presented as part of the symposium entitled “Nutritional Experiences in Early Life as Determinants of the Adult Metabolic Phenotype” at the Experimental Biology 2009 meeting, April 20, 2009, in New Orleans, LA. This symposium was sponsored by the ASN and supported by an unrestricted educational grant from the ASN Nutritional Sciences Council and Milk Specialties Global. The Guest Editor for this symposium publication was Marta Fiorotto. Guest Editor disclosure: no conflicts of interest.

2

Supported by the Biotechnology and Biological Sciences Research Council (to M.S. Martin-Gronert) and a fellowship from the British Heart Foundation (to S.E. Ozanne).

3

Author disclosures: M. S. Martin-Gronert and S. E. Ozanne, no conflicts of interest.