Non‑alcoholic fatty liver disease: A major challenge in type�2 diabetes mellitus (Review)

Abstract

Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in type 2 diabetes mellitus (T2DM) patients, being one of the disorders with a relevant global burden. Cross-sectional studies have shown that patients with T2DM and NAFLD have a higher prevalence of liver fibrosis, compared with the general population. Patients with non-alcoholic steatohepatitis (NASH) and T2DM have an increased mortality and morbidity, therefore they generate substantial health care costs. NASH worsens chronic diabetes complications, and T2DM aggravate the NASH progression to fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). The objectives in NAFLD and NASH therapy are to reduce disease activity, to slow down progression of fibrosis, and to lower the risk factors. Unfortunately, there are no specific validated pharmacological therapies. Several trials have demonstrated that anti-diabetic agents such as thiazolidindiones, sodium-glucose co-transporter inhibitors, glucagon like peptide-1 receptor analogs, or dipeptidyl peptidase-4 inhibitors might have complimentary benefits for patients with NAFLD. Some of the effect on reducing steatosis and fibrosis is explained by the weight loss these treatments produce. A goal in standard care is developing screening tools, early and non-invasive diagnosis methods, studying the pleiotropic effects of drugs, together with newer therapeutic agents, which can target mutual pathogenic mechanisms for diabetes and liver disease. Contents 1. Introduction 2. NAFLD and insulin resistance-lipotoxicity and glucotoxicity 3. NAFLD evaluation and progression 4. Therapeutic management 5. Anti-diabetic agents targeting NAFLD 6. Conclusions

Clinical Model for the Prediction of Severe Liver Fibrosis in Adult Patients with Type II Diabetes Mellitus

“…The clinical score created in this research can help identify severe liver fibrosis in patients with T2DM and support clinicians in deciding whether to send patients for a liver biopsy [ 51 ]. However, according to this score, clinical judgment, including liver biopsies, may still be needed for patients who are not found to have severe fibrosis.…”

To Do One and To Get More: Part II. Diabetes and metabolic dysfunction-associated fatty liver diseases

“…98,101 With combination of blood tests and/or image evaluations, the scoring systems according to anthropometric and biological parameters, such as fatty liver index (including body mass index [BMI], waist circumference, plasma TG level, and GGT), MAFLD fibrosis score, Fibrosis-4 score (including age, AST, ALT, and platelet count for possible cutoff value of 1.3), BARD score, NAFIC score based on clinical parameters, including hematological examination, such as ALT, AST, albumin, platelet counts, and physical examination, such as age, BMI, and medical history, can be applied for those patients at risk to be associated with FLD. 65,66,98 However, the aforementioned scoring system is easily confounded by liver function test and age, and additionally, the cutoff values are also easily changed based on the different studies, leaving an uncertain diagnosis. 104 Many novel biomarkers (serum cytokeratin-18 [CK-18] fragment as an example) and surrogate scores have been reported to target the following components, such as a presence of severity of NAFLD, a prognostic value, and a predictive value not only to stratify the progression and/or treatment response, but these biomarkers may be of high cost, not popular, and need a validation about their reliability and feasibility, 104,105 contributing to uncertainty of the diagnosing MAFLD.…”

“…98 However, excessive accumulation of fat (hepatic steatosis) due to disruption of liver capacity to balance between lipid acquisition (FFA derived from two major sources as lipolysis of triglycerides [TG] in adipose tissue or FFA synthesis from glucose and fructose by de-novo lipogenesis) and discharge mediated by the processes of mitochondrial FFA oxidation or the production of very low-density lipoproteins (V-LDLs) to form hepatocyte ballooning and following lipotoxicity, and all attempt to disrupt the cellular integrity, and in the un-compensatory status, it may lead hepatocyte to die to secret several kinds of chemical mediators and adipocytokines, which activates the stellate cells to procedure connective tissue growth factor and collagen and cause an accumulation in the extracellular matrix, and the parenchyma of liver may be is subsequently replaced by fibroblast, and its-associated fibrotic tissue and collagen deposits. 65,86,98…”

Emergence of SGLT2 Inhibitors as Powerful Antioxidants in Human Diseases

“…NAFLD frequently occurs in obese individuals with insulin resistance and can progress to nonalcoholic steatohepatitis, fibrosis, and cirrhosis [ 134 ]. Oxidative stress [ 135 , 136 , 137 ] and inflammation [ 138 ] are important factors mediating hepatocyte injury in NAFLD. However, not all glucose-lowering agents are beneficial in NAFLD.…”