Periodic Reporting for period 2 - PREVENT-2024 (MOVING FROM BIOMARKERS TO MECHANISM ORIENTED PREVENTION OF CARDIOMETABOLIC DISEASE)
Período documentado: 2022-07-01 hasta 2023-12-31
Just like the responses to treatment of overt disease varies greatly between individuals and needs to be personalized, the effect of primary prevention of cardiometabolic disease (i.e. effect of actions taken years before disease onset) is highly diverse. Partly, this can be explained by varying degree of compliance to preventive therapies (such as physical activity and diet), but also inter-individual biological diversity play a major role. We have identified three novel hormonal cardiometabolic risk factors, which are present in large parts of the population. The current project tests if manipulation and therapeutic alteration of levels of these hormones – specifically in individuals indicated to be at risk by as indicated by value of any of the three hormones- can ameliorate cardiometabolic risk.
Specifically, the objectives are to test if cardiometabolic risk can be reduced by: (1) blockade of the hormone neurotensin, a hormone which promotes fat-absorption and central fat accumulation, (2) suppression of the water regulating and diabetes predictive hormone vasopressin by increasing water intake and (3) altered intravascular compartmentalization or production of the bio-active form of adrenomedullin.
If our goals are achieved, the project will give completely novel tools for personalized (hormone-level guided) prevention of cardiometabolic disease in large subsets of the population. This is of great importance for society in EU and globally as obesity and diabetes increase in occurrence and cardiovascular disease is the most common cause of death.
We and others have shown that high plasma concentration of vasopressin, as measured by copeptin, is consistently independently predictive of future risk of diabetes in healthy individuals. In turn, the most common cause of high vasopressin in the healthy state is a low water intake and in low-water drinkers vasopressin level can be effectively lowered by increasing water intake. In the current project, we therefore undertake a large-scale randomized clinical trial testing if diabetes can be prevented by increasing water intake with 1.5 L daily (vs control therapy) during 12 months in subjects with habitually low water intake and high plasma concentration of vasopressin. Recruitment is finished and results expected Q1 2025.
Studies on the effects of the effects of intravascular compartmentalization and genetic effects on production of bioactive adrenomedullin are ongoing.