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Alloveda Liver Update: Pathophysiological association between NAFLD and type 2 diabetes

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eMediNexus    01 November 2020

Non-alcoholic fatty liver disease (NAFLD) is characterized by non-alcoholic hepatic steatosis. Although hepatic steatosis and steatohepatitis is majorly associated with multiple diseases affecting the liver, such as hepatitis A, B and C, autoimmune hepatitis, hemochromatosis, and hypothyroidism, it has been observed to be highly prevalent in patients with type 2 diabetes mellitus (T2D). Epidemiological surveys suggest that the prevalence of NAFLD in obese adults with T2DM are greater than 70%. This high prevalence is suggestive of the presence of obesity and insulin resistance in T2DM. Evidences documented that alanine aminotransferase, which is responsible for most cases in NAFLD is reported to be more than twice normal in 20% of children with T2DM. 

Though the pathogenesis of NAFLD is still not completely understood, insulin resistance is a crucial contributing factor. In addition, obesity is considered as the most frequent cause of the insulin resistant state. This state of obesity causes alterations in lipid metabolism along with inflammation in adipose tissue and ectopic sites of fat deposition in turn results in insulin resistance, secondary to post-receptor abnormalities in insulin signaling pathways . These increased circulating free fatty acid levels associated with reduced suppression of adipose tissue lipolysis by insulin, causes elevated delivery of free fatty acids to the liver.  This production of free fatty acids causes increase in generation of excess triglyceride in the liver which is aggravated by impaired hepatic fatty acid oxidation secondary to insulin resistance. Glucose content in pre-diabetes or overt diabetics also augments the substrate for triglyceride synthesis. Furthermore, impaired very low density lipoprotein (VLDL) secretion, results from insulin resistance, increases fat deposition in the liver. Thus, insulin resistance is seen commonly with NAFLD in regard to obesity, and NAFLD also progresses in relation with both insulin resistance and a state of excess calorie intake.

It has been observed that there is an elevated risk of NAFLD secondary to diabetes, as well as NAFLD ca be considered a risk factor for developing T2DM. This has been corroborated by a study that showed that while contrasting NAFLD patients with controls, patients who had no diabetes at baseline had more possibilities of developing diabetes and metabolic syndrome, examined after 11 years. Moreover, researches also demonstrated that diabetes can be regarded as independent risk factor causing progression of NAFLD to stages like cirrhosis. Therefore, it is essential to evaluate the effects of diabetes on NAFLD progression to nonalcoholic steatohepatitis (NASH), along with its incidence with diabetes while analysing the association between DM and NAFLD.

Source: Bhatt HB, Smith RJ. Fatty liver disease in diabetes mellitus. Hepatobiliary Surg Nutr. 2015;4(2):101-108.

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