NAFLD and states of insulin resistance

Insulin resistance is tightly linked to NAFLD, particularly in those with Type 2 Diabetes. In this video, Prof. Michael Roden, Germany discusses this link, its origins that can inherited or acquired. He also sheds light on the consequences of insulin resistance.
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Hello, my name is professor Michael. I will be talking today about the role of non-alcoholic fatty liver disease (NAFLD) in the context of states of insulin resistance. Insulin resistance is tightly linked to non-alcoholic fatty liver disease (NAFLD) where almost all patient may they be adults or children with non alcoholic fatty liver disease, who suffer from insulin resistance, which is defined by impaired insulin action in their target tissues in particularly people with type 2 diabetes the most frequent form of diabetes mellitus also have non-alcoholic fatty liver disease (NAFLD) in approximately 70% of people with non-alcoholic that deliver disease, we also find type 2 diabetes.

What is the origin and the consequences of insulin resistance?

It can result of course from certain inherited factors and indeed people with insulin resistance in type 2 diabetes frequently have first degree relatives suffering from type 2 diabetes, but in general, the onset of clinical irrelevant insulin resistance and type 2 diabetes relates to quiet factors. It’s mainly the adiposity or obesity which leads to a higher lipocities meaning break down of triglycerides in this functional adipose tissue as well as reduction of glucose uptake in skeletal muscle which characterizes insulin resistance.The adipose tissue this function really seems to be the key event driving not only insulin resistance but also adipose tissue dysfunction leading to non-alcoholic fatty liver disease (NAFLD) and that relates to local inflammation. Impaired insulin action and flux of metabolites of triglycerides the so-called free fatty acids and glycerol to the liver.

The implications of an invasion of macrophages that characterizes the local inflammation, resulting in impaired insulin action

Let’s see how we can imagine that. The left panel shows you an adipose tissue with the adipocyte and the star represents macrophage which invades the adipose tissue when it is enlarging due to obesity. This invasion of macrophages characterizes the local inflammation and that results to impaired insulin action and the impaired insulin action leads to higher lipolysis, breakdown of triglycerides and in as a result non-esterified fatty acids NIFA or FFA free fatty acids as well as glycerol are shifted by the bloodstream to the hepatocyte, as shown here in the gray color. Within the hepatocytes the fatty acids are either esterified stored as triglycerides which forms the basis of steatosis and non-alcoholic fatty liver disease (NAFLD) or metabolites of the lipids, for example, diacylglycerols, but also – saturated fatty acid metabolize the so called ceramides that interfere with insulin signaling and cause insulin resistance so that there is also an abnormal regulation of glucose metabolism.and in parallel; glycerol, but also metabolites of fatty acids lead to increased oxidation in the mitochondria shown in the green color and also lead to stimulation of new syntheses of glucose gluconeogenesis and that starts the increase in blood glucose, which is the key finding of type 2 diabetes.

Also in prediabetes states we see increased but still within the normal range line glucose concentrations, so that starts a vicious cycle between Type 2 diabetes and a metabolic syndrome, which is characterized by obesity, dyslipidemia, hyperglycemia and hypertension and also non-alcoholic fatty liver disease (NAFLD). So for example, presence of type 2 diabetes increases the risk for cardiovascular disease to twofold and in parallel increases the risk of progressive fatty liver disease liver fibrosis. For example – by two to six-fold.

Conclusion

In parallel, people with non-alcoholic fatty liver disease (NAFLD), but without diabetes have a two point two-fold higher risk for type 2 diabetes and in parallel up to doubled risk for cardiovascular disease. Of course, NAFLD, the simple steatosis or stereotype of hepatitis, has a higher risk for fibrosis and progression to hepatocellular carcinoma. In particular, people suffering from type 2 diabetes have a risk for accelerated progression of fibrosis to cyruses in a higher risk for developing hepatocellular cancer.

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Prof. Michael Roden

Prof. Michael Roden

Professor Dr. Michael Roden is Chair of Endocrinology and Metabolic Diseases, Heinrich-Heine University, Director of the Division of Endocrinology and Diabetology, University Clinics Düsseldorf and CEO of the German Diabetes Center (DDZ). He was trained at University of Vienna and Yale University. His translational studies..

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