Abstract
Reports indicate the increasing prevalence of liver disorders in diabetes mellitus (DM) patients. Clinically, it has also been revealed that the existence of nonalcoholic fatty liver disease (NAFLD) enhances the incidence of type 2 diabetes mellitus (T2DM), while T2DM exacerbates NAFLD to extremely severe forms of steatohepatitis, cirrhosis, and hepatocellular carcinoma. This implies the coexistence and bidirectional nature of NAFLD and T2DM, which function synergistically to drive adverse consequences in clinical practice. For treatment of such comorbid state, though the existing practices such as lifestyle management, traditional Chinese medicines (TCM), and pharmaceuticals have offered somewhat relief, the debate continues about the optimal therapeutic impacts. Recent developments in the field of tissue engineering have led to a renewed interest in novel biomaterial alternatives such as stem cells. This might be attributable to their differentiation potential towards hepatic and pancreatic lineage. These cellular therapies could be further complemented by platelet-derived biomaterials, TCM formulations, or any specific drug. Based on these abovementioned approaches, we aimed to comprehensively analyze various preclinical and clinical studies from traditional to regenerative therapeutic approaches in managing concomitant NAFLD and T2DM.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is highly common in diabetes mellitus (DM), a syndrome characterized by altered glucose metabolism [1], and evidence implies that these concomitant pathologies are bidirectional [2]
NAFLD participates in the development of type 2 DM (T2DM) by elevating glucose production in the liver and aggravating hepatic insulin resistance [3]
Lifestyle management seems a critical factor to reduce glucose production and insulin resistance in the liver and the systemic insulin resistance caused by T2DM
Summary
Nonalcoholic fatty liver disease (NAFLD) is highly common in diabetes mellitus (DM), a syndrome characterized by altered glucose metabolism [1], and evidence implies that these concomitant pathologies are bidirectional [2]. DPP-4 inhibitors like sitagliptin have been suggested effective and safe for DM patients complicated by liver injuries [14], whereas the second-line therapies GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive impact on body weight with reduced risk of hypoglycemia. Based on limitations such as the risk of lactic acidosis and hypoglycemia associated with these oral hypoglycemic agents has prompted the scientific community to explore other safer and efficacious alternatives [15]. Considering challenges and available therapeutic tools for managing concomitant NAFLD and DM, this article has extensively reviewed preclinical and clinical studies from traditional to advanced regenerative therapeutic interventions
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