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Peripheral insulin resistance predicts liver damage in nondiabetic subjects with nonalcoholic fatty liver disease
Author(s) -
Rosso Chiara,
Mezzabotta Lavinia,
Gaggini Melania,
Salomone Federico,
Gambino Roberto,
Marengo Andrea,
Saba Francesca,
Vanni Ester,
Younes Ramy,
Saponaro Chiara,
Buzzigoli Emma,
Caviglia Gian Paolo,
Abate Maria Lorena,
Smedile Antonina,
Rizzetto Mario,
Cassader Maurizio,
Gastaldelli Amalia,
Bugianesi Elisabetta
Publication year - 2016
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.28287
Subject(s) - medicine , nonalcoholic fatty liver disease , insulin resistance , odds ratio , gastroenterology , confidence interval , endocrinology , type 2 diabetes , homeostatic model assessment , cohort , metabolic syndrome , insulin , fatty liver , diabetes mellitus , disease , obesity
Surrogate indexes of insulin resistance and insulin sensitivity are widely used in nonalcoholic fatty liver disease (NAFLD), although they have never been validated in this population. We aimed to validate the available indexes in NAFLD subjects and to test their ability to predict liver damage also in comparison with the NAFLD fibrosis score. Surrogate indexes were validated by the tracer technique (6,6‐D 2 ‐glucose and U‐ 13 C‐glucose) in the basal state and during an oral glucose tolerance test. The best‐performing indexes were used in an independent cohort of 145 nondiabetic NAFLD subjects to identify liver damage (fibrosis and nonalcoholic steatohepatitis). In the validation NAFLD cohort, homeostasis model assessment of insulin resistance, insulin to glucose ratio, and insulin sensitivity index Stumvoll had the best association with hepatic insulin resistance, while peripheral insulin sensitivity was most significantly related to oral glucose insulin sensitivity index (OGIS), insulin sensitivity index Stumvoll, and metabolic clearance rate estimation without demographic parameters. In the independent cohort, only oral glucose tolerance test‐derived indexes were associated with liver damage and OGIS was the best predictor of significant (≥F2) fibrosis (odds ratio = 0.76, 95% confidence interval 0.61‐0.96, P = 0.0233) and of nonalcoholic steatohepatitis (odds ratio = 0.75, 95% confidence interval 0.63‐0.90, P = 0.0021). Both OGIS and NAFLD fibrosis score identified advanced (F3/F4) fibrosis, but OGIS predicted it better than NAFLD fibrosis score (odds ratio = 0.57, 95% confidence interval 0.45‐0.72, P < 0.001) and was also able to discriminate F2 from F3/F4 ( P < 0.003). Conclusion: OGIS is associated with peripheral insulin sensitivity in NAFLD and inversely associated with an increased risk of significant/advanced liver damage in nondiabetic subjects with NAFLD. (H epatology 2016;63:107–116)