Racial health disparities are a pervasive feature of modern experience and structural racism is increasingly recognized as a public health crisis. Yet evolutionary medicine has not adequately addressed the racialization of health and disease, particularly the systematic embedding of social biases in biological processes leading to disparate health outcomes delineated by socially-defined race. In contrast to the sheer dominance of medical publications which still assume genetic “race” and omit mention of its social construction, we present an alternative biological framework of racialized health. We explore the unifying evolutionary-ecological principle of niche construction as it offers critical insights on internal and external biological and behavioral feedback processes environments at every level of organization. We Integrate insights of niche construction theory in the context of human evolutionary and social history and phenotype-genotype modification, exposing the extent to which racism is an evolutionary mismatch underlying inequitable disparities in disease. We then apply ecological models of niche exclusion and exploitation to institutional and interpersonal racial constructions of population and individual health, and demonstrate how discriminatory processes of health and harm apply to evolutionarily relevant disease classes and life-history processes in which socially-defined race is poorly understood and evaluated. Ultimately, we call for evolutionary and biomedical scholars to recognize the salience of racism as a pathogenic process biasing health outcomes studied across disciplines and to redress the neglect of focus on research and application related to this crucial issue.

Type 2 diabetes mellitus is associated with a 2 to 4 times higher risk of a heart attack or stroke. This increased risk of heart attacks and strokes results from an accelerated development of atherosclerotic plaques. During atherosclerotic plaque development, vascular smooth muscle cells (VSMC) proliferate and migrate leading to thickening of the intima of the arterial walls. This process is accelerated in diabetic patients by increase in two miRNAs, miR‐221 and ‐222. These miRNAs are sensitive to changes in insulin receptor (IR) signaling. Under normal conditions, most of IR subunits are bound to insulin‐like growth factor‐1 receptor (IGFR) subunits forming heterodimers, which largely function as IGFR homodimers. A loss of IGFR thus promotes increased IR homodimers and an increase in insulin signaling. Our objective is to evaluate the effect of loss of IGFR on miR‐221 and ‐222 expression in VSMCs. We hypothesize that the loss of IGFR coupled with physiological insulin stimulation promotes increased expression of miR‐221/‐222, which will in turn promote increased VSMC proliferation and migration. IGFR expression was measured in human atherosclerotic plaque samples from diabetic patients and nondiabetic patients. The effects of insulin stimulation coupled with the absence of IGFR was modeled with VSMCs isolated from an VSMC‐specific IGFR knockout mouse. Our data demonstrates that arteries from diabetic subjects exhibit a 5.5‐fold loss of the insulin‐like growth factor receptor (IGFR‐1). Murine vascular smooth muscle cells lacking IGFR exhibit a dose‐dependent increase in miR‐221/222 in response to physiological insulin stimulation. We conclude that loss of IGFR, likely increasing IR holoreceptors, alters insulin signaling to promote increased miR‐221/222 in response to physiological insulin. These data provide support for the loss of IGFR as an initiator of the increase in intimal thickening seen in type 2 diabetes associated with miR‐221/222.