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09-01-2011 | Diabetes | Article

Elevated serum insulin increases NAFLD risk


Free abstract

MedWire News: Study findings show that high fasting insulin levels, indicative of insulin resistance (IR), that continue to increase over time predict a significantly increased risk for nonalcoholic fatty liver disease (NAFLD) in individuals without diabetes.

"The pathogenesis of NAFLD is not currently well understood, but the prevailing hypothesis is the so-called 'two-hit' model that explains the development of steatohepatitis due to IR as the 'first hit' and occurrence of hepatocellular inflammation and fibrosis due to adipocytokines and oxidative stress as the 'second hit,'" say the researchers.

To investigate whether IR in the form of high fasting insulin is linked to increased NAFLD risk, Ki-Chul Sung (Sungkyunkwan University School of Medicine, Seoul, Republic of Korea) and colleagues tested 4954 nondiabetic individuals without NAFLD for glucose and insulin levels at baseline (2003) and after 5 years (2008), as well as evidence of NAFLD at study completion (2008).

By the end of the study, 644 (13%) participants had developed NAFLD. Those in the third (6.11-7.56 IU/ml) and fourth quartiles (7.57 IU/ml or above) of baseline fasting insulin had a respective 44% and 65% increased risk for developing NAFLD at 5 years compared with those in the first quartile (5.12 IU/ml or below).

Individuals who had fasting insulin levels in the third or fourth quartile (high group) at both baseline and 5 years had the highest risk for NAFLD, at a 2.5-fold increase compared with those in the lower two quartiles at baseline and 5 years (low group).

In contrast, participants in the high group at baseline who were in the low group at 5 years only had a 1.2-fold increased risk for having NAFLD at 5 years versus those in the low group throughout the study period. Those initially in the low group who transferred to the high group had a 1.6-fold increased risk compared with the low-low group.

"Risk of future development of NAFLD could be reversed if baseline hyperinsulinemia is reduced, suggesting the reversible and preventive role of interventions to reduce insulin resistance on NAFLD development," conclude the authors in the American Journal of Medicine.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Helen Albert