Nonalcoholic Fatty Liver Disease and Its Complex Relation with Type 2 Diabetes Mellitus—From Prevalence to Diagnostic Approach and Treatment Strategies

Abstract

Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes Mellitus (T2DM) are increasing rapidly worldwide, reaching epidemic proportions. Their association, based on common metabolic risk factors (obesity, insulin resistance (IR), unhealthy lifestyle), brings an additional risk of both hepatic and cardiovascular (CV) adverse clinical outcomes. The terminology of “NAFLD” is stigmatizing to some but not all patients, and a more practical one should be announced soon. Medical strategies can address both diseases simultaneously, as they have crossing pathophysiological mechanisms, mainly IR. Strategies vary from lifestyle intervention and pharmacological options, as more molecules designated for T2DM treatment may be helpful in NAFLD, to surgical procedures. This review focuses on the coexistence of NAFLD and T2DM, pointing out the utility of the appropriate terminology, its prevalence, and mortality rates among the diabetic population. Briefly, we have discussed the main pathophysiological mechanisms and the risk stratification algorithm for the development of NAFLD and nonalcoholic steatohepatitis (NASH) as well as the tools for evaluation of fibrosis. Finally, we have focused on the current therapeutic options for the treatment of NAFLD associated with T2DM.

Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease—Current Background, Hopes, and Perspectives

“…Antihyperglycemic agents supporting weight loss in patients with T2DM have shown beneficial effects in NAFLD [ 20 ]. However, it appears that improvement of glycemic control in patients with co-existent NAFLD and diabetes may be associated with an improvement in NAFLD independently of the lost weight [ 21 ].…”

Blood lactate levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease in type 2 diabetes: a real-world study

“…The close link between T2DM and MAFLD is attributed to their common pathogenic mechanism and metabolic risk factors such as genetic factors, unhealthy lifestyle, insulin resistance, and abnormal lipid metabolism ( 24 ). More importantly, the presence of T2DM further exacerbates the progression of MAFLD and the patients with type 2 diabetes are at a higher risk of hepatic fibrosis and cirrhosis ( 25 , 26 ).…”

Management of metabolic-associated fatty liver disease: The diabetology perspective

“…T2DM, the predominant sequel of MetS, is therefore commonly associated with MAFLD and vice versa because of the similarity in pathogenesis. Various genetic predisposing factors, insulin resistance (IR), proatherogenic dyslipidemia [low levels of high-density lipoprotein cholesterol (HDL-C) as well as elevated concentrations of very low-density lipoproteins, triglycerides, and apolipoprotein B100], and alterations in gut microbiota resulting in intestinal dysbiosis are implicated in the development MAFLD[ 7 ].…”

“…IR, the key factor in the development of both disorders, grossly alters the hepatic glucose and lipid metabolism[ 7 - 9 ]. Fasting hyperglycemia as a consequence of IR and postprandial hyperglycemia from the inability of the liver to store glucose as glycogen are both implicated in the development of hepatic steatosis.…”

“…Metformin therapy in patients with MAFLD has been associated with therapeutic benefits such as alanine transaminase (ALT) and aspartate transaminase (AST) reductions of -2.84 (95%CI: -11.09 to 5.28) and -2.39 (95%CI: -7.55, 2.49), respectively, along with improvements in other biological indicators like lipid abnormalities and body mass index (BMI)[ 43 ]. In patients with T2DM and MAFLD, metformin therapy and lifestyle intervention were associated with a mean weight loss of 4.3%-7.9%, leading to improvements in hepatic IR and glycemic control[ 44 ], though the drug had no efficacy in improving NASH histology[ 7 , 45 ]. Due to the lack of evidence for benefits, the AACE guidelines (2022) do not recommend metformin therapy for patients with NASH though the treatment for diabetes with the drug may be continued in patients with MAFLD and NASH.…”