Ethnic differences in the relationship between insulin sensitivity and insulin response
Abstract:
OBJECTIVE Human blood glucose levels have likely evolved toward their current point of stability over hundreds of thousands of years. The robust population stability of this trait is called canalization. It has been represented by a hyperbolic function of two variables: insulin sensitivity and insulin response. Environmental changes due to global migration may have pushed some human subpopulations to different points of stability. We hypothesized that there may be ethnic differences in the optimal states in the relationship between insulin sensitivity and insulin response.
RESEARCH DESIGN AND METHODS We identified studies that measured the insulin sensitivity index (SI) and acute insulin response to glucose (AIRg) in three major ethnic groups: Africans, Caucasians, and East Asians. We identified 74 study cohorts comprising 3,813 individuals (19 African cohorts, 31 Caucasian, and 24 East Asian). We calculated the hyperbolic relationship using the mean values of SI and AIRg in the healthy cohorts with normal glucose tolerance.
RESULTS We found that Caucasian subpopulations were located around the middle point of the hyperbola, while African and East Asian subpopulations are located around unstable extreme points, where a small change in one variable is associated with a large nonlinear change in the other variable.
CONCLUSIONS Our findings suggest that the genetic background of Africans and East Asians makes them more and differentially susceptible to diabetes than Caucasians. This ethnic stratification could be implicated in the different natural courses of diabetes onset.
Canalization is the way in which organisms develop phenotypic robustness as a response to genetic or environmental perturbations. This process ensures the stability of critical biological processes like blood glucose regulation. Canalization of this trait can be represented by a hyperbolic function of two underlying variables: insulin sensitivity and insulin response, as primarily described by Kahn et al. (1,2).
Global migration in the early history of Homo sapiens placed people in new environments, resulting in novel diets, food scarcity, different climates, and exposure to novel pathogens. These changes may have shifted population averages of factors that influence insulin sensitivity and secretion. They include body size, body composition, energy expenditure, storage, and heat production. As these factors changed, they may have disclosed cryptic genetic variation or adopted novel mutations, leading to disruption of the unique point of stable equilibrium of ancestral populations. As this process continued over hundreds of millennia, specific genetic and environmental perturbations may have pushed some subpopulations to different points of stability (1,3–5).
We hypothesized that there may be ethnic differences in the optimal states in the relationship between insulin sensitivity and insulin response and that these differences may depend on a population’s genetic or evolutionary history. To assess this hypothesis, we performed a systematic review and a meta-analysis of studies of the insulin sensitivity index (SI) and the acute insulin response to glucose (AIRg). Our analysis was done in cohorts in any of the three major ethnic groups: Africans, Caucasians, and East Asians. We found significant differences between the groups.