Natural selection and type 2 diabetes-associated mortality in an isolated indigenous community in the valley of Oaxaca, southern Mexico.

OBJECTIVE: This study tests the hypothesis that natural selection is associated with type 2 diabetes (T2D)-associated mortality and fertility in a rural isolated Zapotec community in the Valley of Oaxaca, southern Mexico.

PARTICIPANTS AND METHODS: Mortality data and related demographic and genealogic information were linked with data for fertility, prereproductive mortality and family history of mortality attributed to T2D. Physician verified T2D mortality (n = 27) between 1980 and 2009 and imputed T2D (n = 70) from cardiovascular mortality (68% random sample) and renal failure (44% random sample). Bootstrapping was used to obtain a robust variance estimate in survival analysis and multivariate analysis of variance.

RESULTS: Estimated maximum natural selection by Crow's Index occurred circa 1930 and was relaxed after this time in the study population. Cox-regression survival analysis of T2D mortality with covariates (family history of T2D, cardiovascular disease, renal failure) indicated a significant hazard ratio (HR = 5.95, 95% CI: 1.38-25.67, p < .008) for the increase in T2D in 2000 to 2009. Survival analysis of imputed T2D resulted in a significant HR of 2.03 (95% CI: 1.08-3.85, p = .01) for the increase in T2D in the 2000 to 2009 cohort (reference group: 1980-1989). Mean number of live born offspring was lower among T2D (n = 27, 4.04 ± 3.85 SD) compared to non-T2D (n = 199, 5.30 ± 3.48) groups (p < .08). Mean number of live born offspring was lower (p = .003) among imputed T2D compared to non-T2D groups (4.10 ± 3.44 vs. 5.62 + 3.50).

DISCUSSION: T2D-associated mortality increased in frequency as natural selection decreased, and favored offspring survival of non-T2D descedants. The results indicated statistically significant directional selection against T2D and imputed T2D to this population isolate.