The "Common Soil Hypothesis" Revisited-Risk Factors for Type 2 Diabetes and Cardiovascular Disease

Abstract

The prevalence and the incidence of type 2 diabetes (T2D), representing >90% of all cases of diabetes, are increasing rapidly worldwide. Identification of individuals at high risk of developing diabetes is of great importance, as early interventions might delay or even prevent full-blown disease. T2D is a complex disease caused by multiple genetic variants in interaction with lifestyle and environmental factors. Cardiovascular disease (CVD) is the major cause of morbidity and mortality. Detailed understanding of molecular mechanisms underlying in CVD events is still largely missing. Several risk factors are shared between T2D and CVD, including obesity, insulin resistance, dyslipidemia, and hyperglycemia. CVD can precede the development of T2D, and T2D is a major risk factor for CVD, suggesting that both conditions have common genetic and environmental antecedents and that they share "common soil". We analyzed the relationship between the risk factors for T2D and CVD based on genetics and population-based studies with emphasis on Mendelian randomization studies.

Keywords: Mendelian randomization; cardiovascular disease; coronary artery disease; genetics; risk factors; type 2 diabetes.

Figure 1

Pathophysiology of type 2 diabetes and cardiovascular disease.

Figure 2

Different types of studies for the identification of risk factors for type 2 diabetes and cardiovascular diseases (MR, Mendelian randomization study).

Figure 3

Mendelian randomization study. Genetic variants or polygenic risk scores are instrumental variables, for example, LDL cholesterol is a modifiable exposure, and coronary artery disease (CAD) is an outcome.