Frontiers in Endocrinology · Oct 30, 2026
Metabolic Dysfunction-Associated Steatohepatitis and Type 2 Diabetes: Insulin Resistance, Liver–Pancreas Crosstalk, and Integrated Therapeutic Strategies
By Wen Jian, Fanci Xie, Lidan Luo et al.
Metabolic dysfunction-associated steatohepatitis (MASH) is the inflammatory and fibrosing form within metabolic dysfunction-associated steatotic liver disease (MASLD). Its clinical course overlaps closely with type 2 diabetes (T2D) because insulin resistance affects adipose tissue, hepatic glucose and lipid handling, pancreatic islet stress, gut-derived signaling, and immune activation. People with T2D have higher rates of steatohepatitis, advanced fibrosis, cirrhosis, hepatocellular carcinoma, and cardiometabolic mortality. MASLD/MASH can in turn worsen insulin resistance and increase the risk of incident or progressive T2D, so the overlap has epidemiological, mechanistic, and therapeutic importance. This review examines the epidemiological, mechanistic, diagnostic, and therapeutic links between MASH and T2D. It first summarizes the bidirectional clinical association between the two conditions. It then reviews the major biological pathways: hepatic insulin resistance and de novo lipogenesis; adipose dysfunction and free fatty acid flux; mitochondrial and endoplasmic reticulum stress; immune-metabolic inflammation; stellate-cell activation; liver–pancreas signaling; and the gut–liver axis. Fibrosis staging is discussed separately because fibrosis, rather than steatosis alone, best predicts liver-related events and mortality. The review also describes a stepwise non-invasive testing pathway for patients with T2D, including the Fibrosis-4 index, vibration-controlled transient elastography, the Enhanced Liver Fibrosis test, and magnetic resonance-based methods. Treatment evidence is organized around lifestyle intervention, incretin-based therapy, resmetirom, sodium-glucose cotransporter-2 inhibitors, peroxisome proliferator-activated receptor agonists, bariatric or metabolic surgery, and anti-fibrotic agents in development. Clinically, MASH in people with T2D requires coordinated endocrinology, hepatology, and cardiometabolic care.