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Impaired insulin clearance linked with hyperinsulinemia, NASH in patients with NAFLD

Impaired insulin clearance was associated with hyperinsulinemia in patients with nonalcoholic fatty liver disease and caused increased liver fat, leading to steatohepatitis, according to recent study results.

Kenneth Cusi, MD, FACP, FACE, division of endocrinology, diabetes and metabolism, University of Florida, and colleagues studied 190 patients who underwent oral glucose tolerance testing to measure insulin clearance and sensitivity and determine relationships between hyperinsulinemia and liver histology.

Kenneth Cusi

The cohort included patients with nonalcoholic steatohepatitis (NASH; n=122) and simple steatosis (SS; n=36) and patients without nonalcoholic fatty liver disease (NAFLD; n=32), who were considered controls. Liver biopsies were performed on all patients but controls.

Patients with NASH had a higher level of fasting plasma insulin (P≤.01), but worse adipose tissue insulin resistance (P=.03) compared with other patients. Patients with SS or NASH had similarly reduced hepatic insulin clearance compared with controls (P<.01), but clearance was similar among those groups with NAFLD (P=.71). No association was observed between reduced hepatic insulin clearance and fibrosis, ballooning or inflammation severity. Worse histological inflammation and ballooning, however, were associated with reduced whole-body insulin clearance (P<.001). There was no difference in insulin secretion between patients with NASH and those with SS.

“Chronic hyperinsulinemia is believed to play an important role in the development of serious comorbidities associated with NAFLD/NASH, such as dyslipidemia and cardiovascular disease,” Cusi told Healio.com/Hepatology. “The work shows that the main determinant of hyperinsulinemia is hepatic fat accumulation per se, even modest degrees, and it is worse if you have very ‘sick’ (insulin resistant) adipose tissue.

“To our surprise, decreased hepatic insulin clearance had little to do with increased insulin secretion (ie, making more insulin to offset insulin resistance) or with the severity of steatohepatitis.”

Disclosure: The researchers report no relevant financial disclosures.