Complex Interplay Between T2D and MASH: Key Drivers and Emerging Treatment Strategies

A recent study suggested that metabolic-associated steatohepatitis can be managed by a multifaceted approach that includes diabetes-related lifestyle modifications, weight loss, and pharmacological management. The study was published in the journal Diabetes Research and Clinical Practice.

Nonalcoholic fatty liver disease (NAFLD) renamed and redefined as metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common non-communicable and global chronic liver diseases. Metabolic dysfunction-associated steatohepatitis (MASH) is the second leading cause of end-stage liver disease occurring due to metabolic imbalances and insulin resistance. There is limited data on the awareness and the potential prognostic implications of MASLD and MASH. Hence, researchers described the multifactorial pathways, the potential complications, and the various management methods in a detailed review.

Risk factors:

• Obesity and visceral adiposity marked by Increased waist circumference and the waist-to-hip ratio are some of the risk factors for MASH.
• Genetic polymorphisms of PNPLA3, TM6SF2, and MBOAT7 have also been implicated.
• A diet containing high fructose, low fiber, high fat, and alcohol are some of the risk factors that can cause intestinal dysbiosis and trigger diabetes-related MASH progression.
• Dyslipidemia and gut dysbiosis are also factors implicated.

Prevalence:

• Studies have shown that diabetics have an increased predisposition to develop advanced fibrosis and MASH.
• A higher cumulative incidence of fibrosis was seen in diabetics over non-diabetics in due course of time.

Progression:

• An interplay between extrahepatic and intrahepatic factors plays a crucial role in diabetes-related MASH progress.
• These include the high-fat diets that trigger intestinal dysbiosis, altered intestinal permeability, altered secretion of adipokines, lipid overload, and proinflammatory cytokines all of which can accelerate hepatic lipid accumulation in MASH.

Therapeutic management:

• The treatment strategies for MASLD or MASH aim to slow down the disease progression, target diabetes complications, reduce morbidity and mortality. 
• Lifestyle modifications, anti-diabetic drugs, thiazolidinediones, SGLT2 inhibitors, Dipeptidyl peptidase-4 (DPP4) inhibitors (DPP4i), Incretin mimetics and co-agonists, thyroid hormone receptor β agonists, and combination therapies have played a crucial role in the management of MASH.

Thus, the study concluded that MASH is a complex condition driven by visceral fat expansion, altered gut microbiota, insulin resistance, increased liver fat, and stress. Lifestyle changes, weight loss, and pharmacology are the multifaceted ways of managing MASH. However, large-scale trials are needed to assess the long-term efficacy.       

Further reading: Gancheva S, Roden M, Castera L. Diabetes as a risk factor for MASH progression. Diabetes Res Clin Pract. Published online September 6, 2024. doi:10.1016/j.diabres.2024.111846