Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) are common conditions that act synergistically to produce adverse outcomes. Combination of both diseases increases the risk of the development of complications of diabetes as well as progression of NAFLD into more severe forms such as cirrhosis, hepatocellular carcinoma and death.

Mounting evidences reported that NAFLD may increase the risk of cardiovascular events by 1.87-fold of an individual with type 2 diabetes. Although no clear data suggests increased mortality, a cohort has shown that NAFLD can have an additive effect on mortality risk. Along with increased cardiovascular risk, co-existent NAFLD increases the risk of microvascular complications of diabetes including chronic kidney disease and retinopathy.

This has been corroborated by a large cohort study that showed the standardised mortality ratio from cirrhosis was increased in diabetics. Another study revealed that, in a series of patients with biopsy proven NAFLD, type 2 diabetes was found to be an independent risk factor for the development of fibrosis. Furthermore, liver biopsies performed in several researches an additive effect of NAFLD and diabetes on cirrhosis, liver and all-cause mortality. 

The management of NAFLD involves reducing modifiable metabolic risk. Good glycaemic control and optimising weight loss are crucial to inhibit progression of disease. However, if cirrhosis has developed, monitor for complications and minimise the risk of hepatic decompensation. Metformin is currently considered as the first line therapeutic agent in the management of patients with type 2 diabetes. Along with reduction in HbA1c, it lowers body fat and improve hepatic insulin sensitivity. In addition, in vitro studies showed activation of AP-activated protein kinase with the help of metformin that results in increased fatty acid oxidation and reduced de novo lipogenesis. Sulphonylureas, commonly used as second line agents for glycaemic control in patients with type 2 diabetes, have shown positive effects in patients with fibrosis in diabetic patients. Thiazolidinediones, another insulin sensitising agents are effective at sensitising adipose tissue to insulin, promoting fatty acid uptake and storage and resulting in the improvement of hepatic steatosis. Moreover, glucagon-like peptide-1 (GLP1) is an insulin mimetic and exhibit extra-pancreatic effects including satiety and increasing insulin sensitivity. In addition to glycaemic control, they are beneficial in reducing obesity and thus, can improves hepatic steatosis and steatohepatitis.

Source: Metabolism. 2016;65(8):1096-1108.