2 | Himalaya Livline | Vol 6 | No. 5 | Sep–Dec 2023 research update Insulin Resistance and Glycated Hemoglobin Level: Principal Contributors to the Pathologic Spectrum of Nonalcoholic Fatty Liver Disease Nonalcoholic fatty liver disease (NAFLD), a major global epidemiologic concern, has gained attention as the hepatic manifestation of metabolic syndrome. The linear link between the metabolic syndrome (partly through glucose intolerance) and hepatic steatosis, fibrosis, and cirrhosis also suggests a close connection between glycemic levels and NAFLD.1,2 Several studies have confirmed that NAFLD elicits a cascade of events that involve impairment of insulin sensitivity and glucose homeostasis and elevation in the levels of liver enzymes (alanine transaminase and g-glutamyl transpeptidase) that predict the onset of type 2 diabetes mellitus.3 While this pathophysiologic interplay is well-documented, studies evaluating the effects of impaired glucose homeostasis on the pathogenesis and progression of NAFLD are underway. Insulin Resistance and Lipotoxicity The pathogenesis of fatty liver can be triggered by increased free fatty acid levels, increased de novo lipogenesis, decreased free fatty acid oxidation, and decreased hepatic triglyceride secretion.4 In addition to promoting glucose uptake by the skeletal muscle, liver, and adipose tissue, insulin suppresses hepatic glucose production. Insulin plays a crucial role in lipid metabolism by promoting fatty acid esterification, storing fatty acids in the form of lipid droplets, and inhibiting lipolysis. Hyperinsulinemia, a response to systemic insulin resistance (IR) by the body, leads to an increase in hepatic de novo lipogenesis.4 IR plays a key role in lipolysis that occurs in the adipose tissue, leading to superfluous free fatty acid trafficking and the development of lipotoxicity. Lipotoxicity impairs insulin signaling, induces oxidative damage, and promotes inflammation and fibrosis. Lipotoxicity is considered as the driving factor in the pathogenic progression of NAFLD.4 Increased intrahepatic lipid accumulation results in triglyceride secretion in the form of very low-density lipoproteins. The accumulating lipids are transported to the adipose tissue, thus, reducing the ability of the adipocytes to store lipids. This series of events that lead to lipotoxicity is found to be associated with the progression from simple steatosis to nonalcoholic steatohepatitis, liver fibrosis, and hepatocellular carcinoma in patients with NAFLD.4 The Role of Elevated Glycated Hemoglobin in NAFLD Glycated hemoglobin (HbA1c) has a unique capacity to reflect the average glucose concentration over the previous 8 to 12 weeks. Substantial evidence from a recent study confirms that diabetic, nondiabetic, obese, and lean individuals with HbA1c > 5.7% are 4 times more prone to developing fatty liver disease.3,5 Insulin Resistance Blood vessel Pancreas Cells do not respond e ciently Insulin
RkJQdWJsaXNoZXIy MjAwNDg=