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Liver function markers predict cardiovascular and renal outcomes in the CANVAS Program.

Giulia Ferrannini1, Norman Rosenthal2, Michael K Hansen3

  • 1Department of Medicine Solna, Karolinska Institutet, Norrbacka, S1:02, 171 76, Stockholm, Sweden. giulia.ferrannini@ki.se.

Cardiovascular Diabetology
|July 5, 2022
PubMed
Summary

In type 2 diabetes, higher gamma-glutamyl transferase (GGT) liver function tests indicate increased cardiorenal risk, while alanine aminotransferase (ALT) is protective. Canagliflozin treatment reduced risk of heart failure and kidney damage.

Keywords:
Alanine aminotransferaseHeart failureLiverRenal morbiditySGLT2 inhibitor

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Area of Science:

  • Cardiology
  • Nephrology
  • Endocrinology
  • Hepatology

Background:

  • Elevated liver function tests (LFTs) are linked to metabolic issues and cardiorenal outcomes.
  • The relationship between LFTs within normal ranges and cardiorenal events needs systematic investigation, especially in type 2 diabetes.
  • The impact of canagliflozin treatment on these associations is also of interest.

Purpose of the Study:

  • To systematically examine the association between LFTs (ALT, AST, GGT, ALP, bilirubin) and cardiorenal outcomes in type 2 diabetes patients.
  • To assess the influence of canagliflozin treatment on these relationships.

Main Methods:

  • 10,142 type 2 diabetes patients' LFTs were measured at baseline and during follow-up.
  • Associations with hospitalized heart failure (HHF), cardiovascular (CV) mortality, all-cause mortality, and renal impairment progression were analyzed.
  • Multivariate proportional-hazards models were used, adjusting for confounders and treatment.

Main Results:

  • Univariate analysis showed ALT was protective, ALP and GGT were associated with adverse outcomes.
  • Multivariate analysis revealed ALT independently associated with lower CV risk, and GGT with higher CV risk.
  • Canagliflozin reduced ALT, AST, and GGT. GGT predicted mortality, ALP predicted renal dysfunction, and canagliflozin reduced HHF and renal risk.

Conclusions:

  • Elevated GGT is a key LFT marker for HHF and mortality risk in high-CV-risk diabetes patients; ALT is protective.
  • Canagliflozin treatment independently reduces the risk of HHF and renal damage.
  • LFTs provide valuable prognostic information in diabetes patients with cardiovascular risk.