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

Abstract

AbstractBackground and AimsWe examined the impact of a co‐diagnosis of metabolic dysfunction‐associated steatotic liver disease (MASLD) and type 2 diabetes (T2D) on patient outcomes.MethodsUsing 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 .1) balanced the cohorts (1:1) for significant covariates. Primary outcomes were cardiovascular, liver, diabetes‐related, and cancer events over 5 years.ResultsAnalysis 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 5 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 5 years from metformin initiation.ConclusionsT2D significantly potentiates the 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.