Metabolic Syndrome Traits Increase the Risk of Major Adverse Liver Outcomes in Type 2 Diabetes

Abstract

OBJECTIVE Type 2 diabetes (T2D) increases the risk for major adverse liver outcomes (MALOs), including cirrhosis and its complications. Patients with T2D frequently have other traits of the metabolic syndrome (MetS). It remains uncertain whether there is a synergistic effect of accumulating MetS traits on future MALO risk. RESEARCH DESIGN AND METHODS Patients with T2D without a history of liver disease were identified from national registers in Sweden from 1998 to 2021. MetS traits included hypertension, low HDL level, hypertriglyceridemia, obesity, and albuminuria, in addition to T2D. MALO events were identified based on administrative coding from national registers until 31 October 2022. Data were analyzed using Cox regression models. RESULTS In total, 230,992 patients were identified (median age 64 years; 58% male), of whom 3,215 (1.39%) developed MALOs over a median follow-up of 9.9 years. Compared with patients with one MetS trait (only T2D) at baseline, those with more than one MetS trait had a higher rate of MALOs (adjusted hazard ratio [aHR] 2.33, 95% CI 1.53–3.54). The rate of MALOs increased progressively with increasing numbers of MetS traits at baseline (aHR 1.28 per added trait, 95% CI 1.23–1.33). During follow-up, patients who acquired additional MetS traits had a progressively higher rate of MALOs. The MetS trait with the largest association with incident MALOs was hypertension (aHR 2.06, 95% CI 1.57–2.71). CONCLUSIONS Having or acquiring additional traits of MetS increase the rate of progression to MALOs in patients with T2D. These results could be used to inform screening initiatives for liver disease.

EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

“…It has been estimated that approximately 10-30% of persons with isolated steatosis progress to steatohepatitis and advanced liver disease, but the risk is much higher in the presence of T2D (42-65% have steatosis) [15,16]. Still, in a Swedish cohort study, the cumulative incidence of major adverse liver outcomes over ten years in individuals with T2D increased with the number of components of the metabolic syndrome, but was still <2% in those presenting with all 5 components [17]. Of note, the presence of steatosis in the general population is not associated with a clinically meaningful increase in the risk of liver-related outcomes, which strongly argues against population-based screening for SLD.…”

“…MASLD is closely linked to and often precedes the development of cardiometabolic risk factors, in particular T2D [33]. Conversely, having several cardiometabolic risk factors confers a greater risk of progressive liver damage and major adverse liver outcomes [17,35]. Age (>50 years), insulin resistance and multiple cardiometabolic risk factors all increase the probability of MASH, severe fibrosis/cirrhosis and both overall and liver-related mortality [36].…”