The synergistic impact of type 2 diabetes and MASLD on cardiovascular, liver, diabetes-related and cancer outcomes

David Rhys Riley, Theresa Hydes, Gema Hernadez, Sizheng Steven Zhao, Uazman Alam, Daniel James Cuthbertson

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims: We examined the impact of a co-diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D) on patient outcomes.

Methods: Using TriNetX, a global federated research network (n=114 million), we undertook two retrospective cohort studies, using time-to-event analysis. Analysis 1 compared MASLD with T2D to MASLD alone; analysis 2 compared T2D with MASLD to T2D alone. Propensity score matching using greedy nearest neighbour (calliper 0.1) balanced the cohorts (1:1) for significant covariates. Primary outcomes were cardiovascular, liver, diabetes-related, and cancer events over five years.

Results: Analysis 1 (n=95,275): a co-diagnosis of T2D significantly increased the risk of ischaemic heart disease (IHD) (HR 1.39; CI: 1.34, 1.44), ischaemic stroke (HR 1.45; CI: 1.35, 1.56), heart failure (HR 1.42; CI: 1.36, 1.49), atrial fibrillation (HR 1.09; CI: 1.03, 1.16), hepatocellular carcinoma (HR 1.96; CI: 1.69, 2.27), pancreatic cancer (HR 1.25; CI: 1.06, 1.48) and liver-related complications over five years from MASLD diagnosis. Analysis 2 (n=15,208): a co-diagnosis of MASLD significantly increased risk of all-cause mortality (HR 1.11; CI: 1.02, 1.22), IHD (HR 1.181; CI: 1.08, 1.29), hepatocellular (HR 50.31; CI: 6.94, 364.72), pancreatic (HR 1.78; CI: 1.12, 2.84), breast (HR 1.43; CI: 1.09, 1.88) and renal cancer (HR 2.01; CI: 1.24, 3.26), and diabetic neuropathy (HR 1.17; CI: 1.09, 1.27) over five years from metformin initiation.

Conclusions: T2D significantly potentiates risk of cardiovascular, malignancy, and liver-related outcomes in people with MASLD. The effect of MASLD on people with T2D, although less dramatic, still potentiated risk of death, IHD, malignancy, and peripheral neuropathy.
Abstract word count: 256

Original languageEnglish
JournalLiver International
Early online date1 Jul 2024
DOIs
Publication statusE-pub ahead of print - 1 Jul 2024

Keywords

  • Cardiovascular disease
  • Neoplasms
  • Non-alcoholic fatty liver disease
  • Type 2 diabetes

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