The Cause-and-Effect Relationship Between Type 2 Diabetes Mellitus and Clinically Overt Cryptogenic Cirrhosis: A Matter That Must Be Seriously Revised

Cirrhosis is defined as the advanced stages of hepatic fibrosis, with characteristic distortion of the hepatic architecture in addition to numerous regenerative nodules. Cirrhosis without an apparent cause is labeled cryptogenic (1, 2). Since metabolic syndrome was identified as a distinct medical entity, and insulin resistance and hyperinsulinemia have been addressed as its fundamental pathophysiologic processes, most cases of cryptogenic cirrhosis have been considered to be linked to non-alcoholic fatty liver disease (NAFLD) of insulin resistance and metabolic syndrome. In this context, type 2 diabetes mellitus (T2DM), a true innocent bystander, was mistaken for a component of active metabolic syndrome or somehow equivalent to it, and with this illusory supposition the medical journals were flooded with papers addressing non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis as the monozygotic twin of T2DM (3-9). Underestimated and usually underreported alcohol consumption on the one hand, and profound de novo impairment of glucose tolerance and mild hyperglycemia in chronic liver failure on the other, have resulted in a confusing situation in which one is not able to clearly determine which comes first: T2DM or cirrhosis.