The liver in diabetes: current state and future perspectives

Diabetes mellitus is strongly associated with metabolic dysfunction-associated steatotic liver disease (MASLD). For many years, MASLD has not been recognised as either a common pathophysiological feature of type 2 diabetes or a diabetes-related complication. This special issue of Diabetologia puts the liver in focus in the context of diabetes. This review discusses current challenges in, and emerging opportunities for, the diagnosis and management of MASLD and fibrosis in type 2 diabetes. Up to 95% of cases of MASLD remain undiagnosed because there are no accepted recommendations for assessing steatosis, whereas non-invasive tests overestimate the prevalence of MASLD progression in type 2 diabetes. Of note, the combination of type 2 diabetes and metabolic syndrome features is a strong predictor of liver disease outcomes, but CVD is the major cause of death in non-cirrhotic MASLD. MASLD is heterogeneous including subtypes linked to common genetic variants, for example PNPLA3 I148M, which increases the risk of liver disease but may protect against CVD. Recent approval of drugs targeting hepatic energy metabolism or promoting weight loss is promising for achieving fibrosis remission, but people with type 2 diabetes will still require complex multifactorial management. Achieving a significant increase in diagnostic rates of at-risk metabolic dysfunction-associated steatohepatitis (MASH) will require a paradigm shift, including greater awareness among clinicians, including diabetologists and endocrinologists, and expansion of community-based diagnostic capabilities accompanied by analyses of the cost-effectiveness of prevention and treatment.