Thrifty phenotype refers to the correlation between low birth weight of neonates and the increased risk of developing metabolic syndromes later in life, including type 2 diabetes and cardiovascular diseases. Although early life undernutrition is thought to be the key driving factor to the hypothesis, other environmental factors have been explored for their role in susceptibility, such as physical inactivity. Genes may also play a role in susceptibility of these diseases, as they may make individuals predisposed to factors that lead to increased disease risk.
Historical overview
The term thrifty phenotype was first coined by Charles Nicholas Hales and David Barker in a study published in 1992. In their study, the authors reviewed the literature up to and addressed five central questions regarding role of different factors in type 2 diabetes on which they based their hypothesis. These questions included the following:
The role of beta cell deficiency in type 2 diabetes. The extent to which beta cell deficiency contributes to insulin intolerance. The role of major nutritional elements in fetal growth. The role of abnormal amino acid supply in growth limited neonates. The role of malnutrition in irreversibly defective beta cell growth.
From the review of the existing literature, they posited that poor nutritional status in fetal and early neonatal stages could hamper the development and proper functioning of the pancreatic beta cells by impacting structural features of islet anatomy, which could consequently make the individual more susceptible to the development of type 2 diabetes in later life. However, they did not exclude other causal factors such as obesity, ageing and physical inactivity as determining factors of type 2 diabetes.
In a later study, Barker et al. analyzed living patient data from Hertfordshire, UK, and found that men in their sixties having low birthweight (2.95 kg or less) were 10 times more likely to develop syndrome X (type 2 diabetes, hypertension and hyperlipidemia) than men of the same age whose birthweight was 4.31 kg or more. This statistical correlation was independent of the gestation period and other possible confounding factors such as current social class or social class at birth, smoking, and consumption of alcohol. Furthermore, they argued that they were likely to underestimate this association, since they could only sample the surviving patients, and patients having more severe manifestations of syndrome X were less likely to survive to that age.
In 1994, Phillips’ et al. found statistically significant association between thinness in birth (measured as Ponderal index) and insulin resistance, the association being independent of length of gestation period, adult body mass index, and confounding factors like then-current social class or social class at birth.
In 2001, Hales and Barker updated the hypothesis by positing that the thrifty phenotype may be an evolutionary adaptation: the thrifty phenotype responds to fetal malnutrition by selectively preserving more vital organs of the body and preparing the fetus for a postnatal environment where resources will be scarce.
Evolutionary rationale
Offspring
Maternal nutrition can affect the development of the unborn child in poor nutritional environments such that it will be prepared for survival within that poor environment. This results in a thrifty phenotype (Hales & Barker, 1992). It is sometimes called Barker's hypothesis, after Professor David J. P. Barker, researching at the University of Southampton who published the theory in 1990.
Metabolic
The thrifty phenotype hypothesis says that early-life metabolic adaptations help in survival of the organism by selecting an appropriate trajectory of growth in response to environmental cues. An example of this is type 2 diabetes. In their review, Barker and Hales discuss evidence that beta cells abnormally develop due to malnutrition during fetal development, causing insulin abnormalities later in life. The review also notes that low birth weight alone does not necessarily mean that it is a manifestation of thrifty phenotype. Since low birth weight is not exclusively caused by maternal malnutrition, meaning that other factors could influence the low birth weight–disease relationship.