Research Funding AgreementJANSSEN (DSB.AD003.059)

Area tematica

Scienze biomediche

Area progettuale

Struttura responsabile del progetto di ricerca

Istituto di fisiologia clinica (IFC)

Responsabile di progetto

GIORGIO IERVASI
Telefono: 0503152016
E-mail: iervasi@ifc.cnr.it

Abstract

The early separation of the Kaplan-Mayer plots of incident cardiovascular death and hospitalization for heart failure in both EMPA-REG (1) and CANVAS (2) is coherent with the idea that active treatment may prevent impending cardiac decompensation (12). A large body of evidence, clinical and experimental, supports the notion that ketone bodies are a preferred energy substrate for the heart and may provide a thrifty fuel for the energy-starved failing heart (13). Circulating ketone bodies were not measured in EMPA-REG and could therefore not be included in a mediation analysis of cardiovascular death (14). CANVAS offers the unique opportunity to test the potential role of SGLT2i-induced mild hyperketonemia in reducing the heart failure burden of patients with type 2 diabetes.

Obiettivi

Objectives:
Primary objective:
o To test the hypothesis that canagliflozin-induced increases in circulating ketone levels may impact the risk of cardiovascular death and hospitalization for heart failure (HHF) in CANVAS

Secondary objectives:
o To test the hypothesis that canagliflozin-induced increases in circulating ketone levels may relate to the risk of progression of nephropathy in CANVAS
o To test the relationship of baseline ketone levels with risk of progression to CV or renal outcomes
o To test relationship of changes in circulating ketone levels to other metabolic changes (body weight, fasting glucose, HbA1c) in CANVAS
o To test whether active treatment is associated with an increase in the mitochondrial redox state as reflected by the ß-hydroxybutyrate/acetoacetate ratio

Data inizio attività

17/12/2018

Parole chiave

canvass

Ultimo aggiornamento: 20/04/2024