Fatty liver adds to cardiovascular risk in obese type 2 diabetics

Last Updated: 2016-02-22

By Megan Brooks

NEW YORK (Reuters Health) - Nonalcoholic fatty liver disease (NAFLD) in obese patients with type 2 diabetes is associated with an unfavorable metabolic profile, new research shows.

"Having fatty liver really adds to your cardiovascular risk significantly in the sense that you are more insulin resistant and your lipid profile is worse," Dr. Kenneth Cusi, chief of the Division of Endocrinology, Diabetes and Metabolism, the University of Florida, Gainesville, told Reuters Health by phone.

These patients "probably need intensified management, not only diabetes management, but cardiovascular risk management," he said.

NAFLD and its more severe form with nonalcoholic steatohepatitis (NASH) are increasing rapidly in parallel with the increase in obesity and type 2 diabetes mellitus (T2DM), but the metabolic consequences are unclear, the investigators note in Diabetes Care online February 9.

To investigate, they studied 136 obese patients with T2DM (50 without NAFLD, 21 with isolated steatosis (no liver inflammation) and 65 with NASH, the more severe form of fatty liver with inflammation and fibrosis). They also studied 18 obese patients without T2DM or NAFLD and 10 nonobese healthy controls as a reference for metabolic measurements. They combined "state-of-the-art" metabolic measurements with quantification of intrahepatic triglycerides and liver histology.

They observed that, in obese T2DM patients, the development and progression of liver disease (from without NAFLD to isolated steatosis to NASH) are associated with more dysfunctional and insulin-resistant adipose tissue.

"This finding highlights the important role of 'sick adipose tissue' (also known as lipotoxicity, a damage to other tissues like the liver from fat chronically delivered from sick adipose tissue) in the development and progression of NAFLD. Supporting this concept, diminished insulin action of adipose tissue correlated strongly with the amount of intrahepatic triglycerides, as well as with the severity of liver disease on histology," Dr. Cusi explained in email.

They also note that in obese non-diabetic patients, the hepatic insulin resistance index, a measure of liver insulin resistance in the fasting state, was already roughly 30% worse in obese control patients relative to nonobese controls without a fatty liver. However, it was the patients with T2DM and NASH that had the most significant impairment in hepatic insulin sensitivity, the investigators say.

The presence of NASH in obese diabetic patients was also associated with more severe hypertriglyceridemia but with no differences in blood pressure or glycemia, they found.

"These results have important clinical implications, as they suggest that identification of patients with T2DM and NASH may highlight a subgroup of subjects in need of early and/or more aggressive lipid-lowering therapy and cardiovascular risk factor management," the authors write.

Dr. Cusi told Reuters Health, in a prior study (http://bit.ly/1KZSyQ5), "We showed that half of our patients with diabetes already have fat in the liver even at what we consider to be normal liver enzymes."

The presence of NAFLD in type 2 diabetic patients continues to be overlooked by clinicians, the authors note in their paper. "Most primary care doctors and even endocrinologists are not screening for this routinely in the clinic. Right now, there is not an ideal way to do this," Dr. Cusi said.

He thinks physicians should have a lower threshold for screening patients with type 2 diabetes for NAFLD/NASH. "Doctors need to be aware that this can go under the radar," he said. "You can order a liver ultrasound, and if that is positive, then talk with the hepatologist and see if the patient deserves more noninvasive procedures, like Fibroscan, or a liver biopsy, both of which allow you to see if there is scarring in the liver or fibrosis. And, of course anybody with elevated ALT (alanine aminotransferase), typically in NASH roughly 50% greater than the AST (aspartate aminotransferase), deserves special attention."

The study had no commercial funding and the authors have no relevant disclosures.

SOURCE: http://bit.ly/1SX3xNi

Diabetes Care 2016.