Ethnic differences in the relationship between insulin sensitivity and insulin response: a systematic review and meta-analysis

Keiichi Kodama, Damon Tojjar, Satoru Yamada, Kyoko Toda, Chirag J Patel, Atul J Butte, Keiichi Kodama, Damon Tojjar, Satoru Yamada, Kyoko Toda, Chirag J Patel, Atul J Butte

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.

Figures

Figure 1
Figure 1
Flow diagram of literature search and cohort identification.
Figure 2
Figure 2
Ethnic differences in the relationship between insulin sensitivity and insulin response in NGT cohorts. Scatter plot of SI vs. AIRg measured in NGT (healthy) African, Caucasian, and East Asian cohorts. Each circle represents one study cohort. Circle area is proportional to cohort sample size. The solid line is the curve calculated in our meta-analysis [ln(AIRg) = –0.915 × ln(SI) – 2.82]. The dashed line is the curve of Kahn et al. (2) describing healthy individuals who were primarily Caucasian [ln(AIRg) = –1.0 × ln(SI) – 3.80].
Figure 3
Figure 3
Ethnic differences in the relationship between insulin sensitivity and insulin response across glucose tolerance subgroups. Plot of mean ± 95% CI values of SI vs. AIRg measured in NGT (circles), IGR (triangles), or T2D (squares) subjects across three ethnic cohorts.

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