Migrational Adaptation and Current Diabetes and Overall Mortality among Various United States and Worldwide Races/Ethnicities

Research Article

Austin Diabetes Res. 2016; 1(1): 1001.

Migrational Adaptation and Current Diabetes and Overall Mortality among Various United States and Worldwide Races/Ethnicities

Charles MA1*, Charles RC2, Kane JP3, Hui G4 and Wong ND4

¹Department of Medicine, University of California, San Francisco, USA

²School of Medicine, University of Minnesota, USA

³Department of Medicine and Cardiovascular Research Institute, University of California, USA

4Departments of Epidemiology and Medicine, University of California, Irvine, USA

*Corresponding author: Charles MA, Department of Medicine, University of California, San Francisco, USA

Received: February 17, 2016; Accepted: March 25, 2016; Published: March 29, 2016


Out of Africa migrations ~60,000 years ago led to widespread populating of Earth. Ancient migration distances appear related to medical observations including diabetic risk alleles and altitude adaptation. Our objective is to show that ancient migration distance is related to current survival. We measured migration distances and correlated these with diabetes and other US mortality rates and international life expectancy among various racial/ethnic groups. For diabetes there are strong, negative correlations with US mortality rates of ethnic groups and migration distance (r= - 0.70, p< 0.00059), which are confirmed using overall US mortality rates (r=-0.84, p<1x105). There is further confirmation using cardiovascular mortality (r= - 0.86), cancer (r= - 0.71) and sepsis (r= - 0.73). A second data set, World Health Organization 2012 life expectancy data from 192 countries confirm the above US correlations showing a moderate, positive correlation with migration distance (r= 0.41, p < 3 x 10-8 ). R2 analysis indicates that 71% (95% CI=0.48-0.90) of the overall US mortality rate is related to migration distance. When evaluating worldwide life expectancy, migration distance retains 17% (95% CI=0.07-0.27) of its effect on survival. Our data are consistent with migrational adaptation being associated with enhanced US diabetes and other disease survivals for some ethnicities. There is superimposition of substantial influences of current healthy lifestyles/effective health care policies from life expectancy analyses. These interrelationships suggest the dimension of migrational adaptation be further evaluated in the demography of survival research and public health care policy.

Keywords: Out of Africa migration; Diabetes mortality rates; Ancient migration and survival


Eighty to ninety percent of diabetic mortality is due to cardiovascular disease. Cardiovascular disease is also overwhelmingly the leading cause of death in the US and other Western societies. Interestingly cardiovascular disease burden or risk factor load appears discordant with mortality rates in certain ethnic groups such as Hispanics and African-Americans. For example Hispanics aged 18 and over or in the Medicare population have increased cardiovascular disease burden, e.g., diabetes, compared to whites [1,2], but paradoxically Hispanics have less diabetes, cardiovascular and overall mortality [2-4]. This phenomenon has been known for over 2 decades and is referred to as the Hispanic paradox [4,5]. Similar paradoxical results have recently been reported in a Veterans Administration population, where African-Americans have increased cardiovascular disease burden (diabetes & hypertension) compared to whites, but similar or reduced cardiovascular mortality [6]. These paradoxical observations led some authors to suggest that genetic factors may be involved.

There are estimates that ~60 thousand years ago (kya) modern humans migrated out of Africa [7]. These migrations are associated with structural genetic variation thought to be modulated by demographic and biological dimensions. For example during migration there is a decrease in genetic diversity consistent with serial founder effects, in which successive migrations, likely caused by local environmental constraints, result in small groups expanding into new areas [8,9]. Further worldwide population genomic structural data are consistent with genetic drift at neutral loci, but accelerated divergence at other loci due to local selection adapting to a broad range of environments creating local phenotypic variation [8,10,11]. Thus new or existing alleles can occur at low frequencies, but in specific environments selective pressure can result in allelic enrichment, which can influence phenotypic expression.

Parallel Genome-Wide Association Studies (GWAS) in regional geographic areas have identified genetic disease risk alleles involved in a myriad of worldwide diseases. These dual sets of above observations of worldwide genetic variance and GWAS should influence our understanding of diseases and thus survivability, and the role that migrational adaptation has in defining these processes. However, diabetes survival has not been evaluated in a worldwide context. Since migration into new and distant geographical areas presents unique environmental stressors engendering adaptation, we now hypothesize that migrational adaptation affects current diabetes survival. The rationale for this hypothesis is that those who migrate farther are likely to experience diverse and accumulating adverse environmental conditions including a) dietary challenges, b) climate and altitude, c) pathogen load and d) hostile humans and animals that evoke genetic alterations influencing disease risk and survival. That diet and climate affect specific allele enrichment related to local adaptation is supported by recent genetic structural studies [11].

Supporting our hypothesis are several apparently disparate, but specific genetically linked phenotypic observations that appear geographically determined from both worldwide and local genetic perspectives. Although there appears to be no reports of specific genetic associations related to mortality in African-American or Hispanic populations, genetic associations for cardiovascular disease burden, such as diabetes have been observed. For example assessment of nDNA alleles related to diseases, e.g., type 2 diabetes, indicate that risk allele frequencies change as migration distance increases out of Africa into Asia and the New World, which appears importantly unrelated to genetic drift [10,12]. As humans migrated into different regions, unrelated groups from different geographical areas independently founded identical alleles more than once, and that risk events appear cumulative and continuous rather than being caused by a single genetic differentiation event [8,10].

Further, evaluation of specific high-risk alleles at the local geographic level permits more genetic and phenotypic detail indicating increased disease risk suggesting that regional, more homogeneous ethnic populations can have uniquely high frequency alleles that appear to drive diseases thought to be polygenic. For example increased diabetes Odds Ratio [OR] of 1.29 in Mexicans is associated with a high frequency (0.50) haplotype, which could account for a 26% diabetes prevalence [13]. This haplotype is rare in Africans and Europeans, present in ~10% of Asians and is attributed to ancient migrations. The extant haplotype’s 5 common Single Nucleotide Polymorphisms (SNPs) originated ~800 kya, and are found in a Neanderthal genome indicating substantial selective pressure to maintain these alleles during migration. Such conservation is possibly related to fuel storage efficiency or innate immunity in response to reduced food availability, since the key gene, SLC16A11, appears primarily active in the liver, and when expressed in HeLa cells results in intracellular triglyceride accumulation [13]. Another risk allele causing premature termination in the TBC1D4 gene, which is related to insulin resistance in skeletal muscle, is found in high frequency (0.17) among Inuits of Greenland, where the diabetes risk OR is a striking 10.3 [14]. This allele is not found in Danish or other Europeans, Chinese or African-Americans. These findings are attributed to natural selection or genetic drift.

Finally, mtDNA haplogroups are differentiated along specific migration routes [15]. mtDNA variants thought to be related to migration and adaptation appear beneficial in certain environments and detrimental in others. For example variant 3394C coding for complex1 protein of the oxidative phosphorylation (OXPHOS) pathway, when present on the M9 haplogroup results in highly coupled OXPHOS due to increased complex1 activity; beneficial for high-altitude Asians [16]. The same 3394C variant on the M9 haplogroup among Asians living at lower altitude is associated with decreased complex1 activity and an increase in Leber hereditary optic neuropathy [16].

Each of the above examples relates to disease risk and appears related to migrational events, whereas herein we present novel correlations with the aim of comparing migration distance with mortality/survival. Our preliminary correlations support the hypothesis that migrational adaptation leads to enhanced current human survival in some races, which suggest that our results may have public health implications.


Mortality rate acquisition

Several criteria were used to acquire a representative cross section of US survival studies: a) reports were limited to print published national data sets, b) federal governmental, peer-reviewed private and academic reports provide a broad base of mortality rates, c) reports were required to have 4 or more racial/ethnic groups and both genders included, d) multiple age groups were included in overall mortality rate reports, e) mortality rates reported in the last 6 years were used in 7 of 9 studies; all studies were reported within 12 years, f) mortality rate categories used for confirmation of diabetes US mortality rates included only entities that appeared related to potential natural selection, g) mortality rate categories included the top ten causes of US mortality, h) a second data set using a worldwide, national life expectancy table was used to compare with overall US mortality, i) the latter data used average age at death from birth and both genders and j) all mortality rate and life expectancy data are accessible from provided references.

Migration distance acquisition

Migration distances for mortality rate and life expectancy correlations were estimated by determining the length of travel distance along reported, consensus patterns of travel routes (Figure 1) using map distance legends (Table 1). Migration distances are in part underestimates due to sea levels at that time, but the differences between various racial/ethnic groups highlighted herein are of the order of 2-10 fold, thus these estimates appear reasonably valid.