Type 2 diabetes and cardiovascular disease (CVD) commonly coexist. Both conditions share many overlapping risk factors, which suggests a shared pathological ground. It is widely known that several hormones regulating cardiovascular function, such as B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP), endothelin-1 (ET-1), adrenomedullin (ADM), and arginine vasopressin (AVP) are implicated in the development of CVD. Less recognised is the fact that these hormones also have metabolic actions. For example, BNP, ANP and ADM were shown to ameliorate insulin resistance, while ET-1 and AVP could promote insulin resistance and glucose intolerance.
Using data from several population-based studies, this doctoral thesis examined the hypothesis that cardiovascular hormones could be implicated in the development of type 2 diabetes. The specific research questions were addressed in three papers constituting the basis of this doctoral thesis.
The first paper assessed whether the cardiovascular hormones ANP, ET-1, ADM, and AVP, were associated with impaired glucose metabolism. We found that elevated circulating concentrations of ANP were associated with a lower incidence of type 2 diabetes, while elevated circulating concentrations of AVP were associated with a higher incident prediabetes and type 2 diabetes. We also observed that the elevated circulating concentrations of ET-1 and ADM were associated with an increase in insulin-related traits.
In the second paper, we investigated whether the natriuretic peptides BNP and ANP could lower the risk of type 2 diabetes and specifically assessed whether the link between both natriuretic peptides and risk of type 2 diabetes could be modified by the presence of CVD. Our results demonstrate that higher concentrations of BNP and ANP were associated with a lower incidence of type 2 diabetes. Here, using a large sample size, we were able to expand the current knowledge by showing that the inverse association with incident type 2 diabetes for BNP was modified by the presence of CVD, while similar differences were not seen for ANP. Analyses using genetic data further suggest that associations of higher concentrations of both BNP and ANP with a lower incidence of type 2 diabetes could probably be causal.
Expanding the results from the first paper, in the third paper we further examined whether ET-1 and ADM could increase the risk of type 2 diabetes. We observed that elevated concentrations of ET-1 and ADM were associated with a higher incidence of type 2 diabetes, but analyses using genetic data suggest a probable causal link for ET-1 only. Furthermore, the findings of this paper provided new evidence that the positive association between ADM and incident type 2 diabetes was more apparent in obese than in non-obese individuals.
In summary, this thesis highlights the importance of cardiovascular hormones beyond CVD. The findings suggest that several cardiovascular hormones play important roles in the development of type 2 diabetes and raise the possibility that targeting these cardiovascular hormones might be effective in preventing and managing not only CVD but also type 2 diabetes
