Metabolic Ghetto

The staggering increase in the prevalence and incidence of metabolic syndrome and its various components is especially alarming amongst minority populations worldwide and within the United States. For example, the prevalence of Type 2 diabetes has doubled in India in the last 30 years, obesity rates have increased 3 fold or more since 1980 in Middle East and the Pacific Island, approximately 11.6% of the Chinese are diabetic, and in the United States the prevalence of diabetes is the highest amongst Hispanic and African American populations. What is the cause of the staggering increase in metabolic diseases within these populations? I recently came across a fascinating hypothesis that talks about the characteristics of a ghetto – community of socially, legally, economically restrained minorities that tend to reproduce themselves over generations – to explain the increasing prevalence of metabolic diseases in these communities.

As I talked about in an earlier post, human beings respond to environmental stimuli over a range of timescales. In between the slow moving evolutionary change and rapid physiological changes we have genomic modifications that mediate responses in the timescale of months, years, and generations. Interestingly, the majority of this plasticity occurs during intra-uterine and infant developmental stages and the ability to adapt is lost after late infancy. Offspring traHumanAdaptationck maternal phenotype (stature, lean tissue) especially when the maternal phenotype is limited due to malnourishment and their growth is strongly guided by maternal phenotype as the energy costs are met from maternal sources. The primary adaptation of the fetus is to align his/her metabolism with the maternal phenotype and all subsequent adaptations occur within the context of this primary adaptation. Consequently, offspring metabolic capacity bears a strong imprint of maternal phenotype. For example, offspring stature at 2 years age is the best predictor of phenotype quality. This last fact is a potentially important factor in the rapid rate of increase in metabolic syndrome within minority populations.

These populations have historically been under-nourished and calorically depleted, and therefore, have developed epigenetic alterations that facilitate maximal energy storage from carbohydrate and fat sources. Consequently, they are developmentally inclined to become insulin resistant and prone to central adiposity as a strategy for a calorie deficient environment.  This programming is a consequence of the maternal phenotype that the fetus was exposed to, which in turn was related to phenotype of the grandmother. These alterations are passed from one generation to the next as non-genetic modes of adaptation. Now as these communities are rapidly transitioning into calorically dense environments, their more efficient metabolic capacity serves to be maladaptive and they develop the hallmarks of metabolic syndrome – T2DM and central adiposity – in adulthood. Patterns of the prevalence of metabolic syndrome are highest in low socioeconomic status in the United States and also in lower socioeconomic societies worldwide that are transitioning into more affluence. The common denominator in these two communities is the transition from calorically undernourished states to calorically dense nutritional environments.

Too rapid an exit from the metabolic ghetto overloads the capacity for adaptivScreen Shot 2015-04-21 at 8.00.06 AMe physiological adjustments and also results in adverse phenotypic consequences in the form of metabolic syndrome. Therefore, as public policies such as United Nation’s Millenium Development Goals to eradicate poverty and hunger is enacted, it is equally important to ensure that these communities are not supplied calorically dense food sources that will subject future generations with the burden of metabolic diseases. Similarly, public health campaigns in communities that have already transitioned from a calorically undernourished state should equally focus on calorie source, content, and expenditure to impede the insidious trans-generational propagation of metabolic syndrome.


2 thoughts on “Metabolic Ghetto”

    1. “…We as individuals must always be aware that our default evolutionary setting is energy conservation, and furthermore, our current cultural paradigm facilitates energy accumulation. Consequently, we must always be looking at this energy balance equation and monitor (admittedly coarse) metrics such as steps, weight, BMI, and body fat percentage. Additionally, we must always be aware of the traps put forth by the food industry and learn to thoroughly weed through the confusing data printed on nutritional labels.”

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