Maternal and In Utero Determinants of Type 2 Diabetes Risk in the Young
- 442 Downloads
The global prevalence of diabetes mellitus has reached epidemic proportions. In 2010, it was estimated that 6.4 % of the adult population (285 million) have diabetes. In recent years, the incidence of type 2 diabetes (T2D), a condition traditionally associated with aging, has been steadily increasing among younger individuals. It is now a well-established notion that the early-life period is a critical window of development and that influences during this period can “developmentally prime” the metabolic status of the adult. This review discusses the role of maternal and in utero influences on the developmental priming of T2D risk. Both human epidemiological studies and experimental animal models are beginning to demonstrate that early dietary challenges can accelerate the onset of age-associated metabolic disturbances, including insulin resistance, T2D, obesity, hypertension, and cardiovascular disease. These findings show that poor maternal nutrition can prime a prediabetes phenotype, often manifest as insulin resistance, by very early stages of life. Thus, the maternal diet is a critical determinant of premature T2D risk. While the mechanisms that link early nutrition to age-associated metabolic decline are currently unclear, preliminary findings suggest perturbations in a number of processes involved in cellular aging, such as changes in longevity-associated Sirtuin activity, epigenetic regulation of key metabolic genes, and mitochondrial dysfunction. Preliminary studies show that pharmacological interventions in utero and dietary supplementation in early postnatal life may alleviate insulin resistance and reduce T2D risk. However, further studies are warranted to fully understand the relationship between the early environment and long-term effects on metabolism. Such mechanistic insights will facilitate strategic interventions that prevent accelerated metabolic decline and the premature onset of T2D in the current and future generations.
KeywordsDevelopmental origins of health and disease Type 2 diabetes Metabolic syndrome Maternal diet Aging Maternal In utero
Compliance with Ethics Guidelines
Conflict of Interest
Kimberley D. Bruce declares that she has no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
- 7.Mayer-Davis EJ, Bell RA, Dabelea D, D'Agostino Jr R, Imperatore G, Lawrence JM, et al. The many faces of diabetes in American youth: type 1 and type 2 diabetes in five race and ethnic populations: the SEARCH for Diabetes in Youth Study. Diabetes Care. 2009;32 Suppl 2:S99–S101.PubMedCrossRefGoogle Scholar
- 8.Hayman LL, Williams CL, Daniels SR, Steinberger J, Paridon S, Dennison BA, et al. Cardiovascular health promotion in the schools: a statement for health and education professionals and child health advocates from the Committee on Atherosclerosis, Hypertension, and Obesity in Youth (AHOY) of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2004;110:2266–75.PubMedCrossRefGoogle Scholar
- 33.Mayeur S, Lancel S, Theys N, Lukaszewski MA, Duban-Deweer S, Bastide B, et al. Maternal calorie restriction modulates placental mitochondrial biogenesis and bioenergetic efficiency: putative involvement in fetoplacental growth defects in rats. Am J Physiol Endocrinol Metab. 2013;304:E14–22.PubMedCrossRefGoogle Scholar
- 40.••Catalano PM, Presley L, Minium J, Hauguel-de MS. Fetuses of obese mothers develop insulin resistance in utero. Diabetes Care. 2009;32:1076–80. This study took metabolic and anthropomorphic measurements from offspring of either obese or lean mothers within 24 h of caesarean section delivery. It showed that fetuses of obese mothers developed insulin resistance in utero and suggested that maternal obesity causes a metabolic compromise already present at birth.PubMedCrossRefGoogle Scholar
- 49.de Rooij SR, Roseboom TJ. The developmental origins of aging: study protocol for the Dutch famine birth cohort study on aging. BMJ Open. 2013. doi: 10.1136/bmjopen-2013-003167.
- 59.••Dolinsky VW, Rueda-Clausen CF, Morton JS, Davidge ST, Dyck JR. Continued postnatal administration of resveratrol prevents diet-induced metabolic syndrome in rat offspring born growth restricted. Diabetes. 2011;60:2274–84. Resveratrol is a plant-derived insulin-sensitizing modulator of the longevity-associated Sirtuin proteins. In growth-restricted offspring, administration of resveratrol reduces fat mass, restores dyslipidemia, and ameliorates insulin resistance and is therefore a potential therapy for early-onset T2D.PubMedCrossRefGoogle Scholar