This project investigates the hypothesis that nutrient intake contributes to metabolic disease (hypertension and diabetes) but only when it exceeds person-specific thresholds, shaped by ancestral adaptation to resource scarcity.
Hypertension: We hypothesize that salt intake raises arterial pressure and contributes to cardiovascular disease (CVD), but only beyond an individual threshold. This threshold-and an associated arterial pressure set point-is traced back to ancestral sodium availability.
Objectives:
(i) Develop a physiological model incorporating the threshold mechanism.
(ii) Examine the model’s implications for the arterial pressure-sodium intake and CVD-sodium intake associations.
(iii) Validate the mechanism by testing whether CVD increases with sodium intake, but only in salt-sensitive individuals.
Diabetes: We hypothesize that caloric intake raises BMI and contributes to diabetes, but only beyond a person-specific threshold that is determined by ancestral caloric availability.
Objectives:
(i) Build a physiological model of diabetes that incorporates this threshold.
(ii) Test the model’s implications for BMI-caloric intake and diabetes-caloric intake associations.
(iii) Validate the mechanism by checking whether diabetes risk increases with caloric intake, but only for individuals who have crossed their threshold.
Scientific Rationale:
Conflicting findings on the link between sodium intake, arterial pressure, and CVD are explained by heterogeneity in sodium sensitivity in our model, which arises due to underlying person-specific set points. This implies nonlinear (discontinuous) sodium intake-arterial pressure-CVD associations that we will test. Variability in the BMI-diabetes association across individuals and ethnic groups is explained in our model by heterogeneity in BMI set points, rather than by other risk factors. This implies nonlinear (discontinuous) caloric intake-BMI-diabetes associations that we will test.