Patients with NAFLD are characterized by insulin resistance (IR) and hyperinsulinism. However, prior studies have been unable to predict NAFLD based on IR measurements. The aim of this study was to explore the application of a newly validated measurement of intact insulin by mass spectrometry to predict NAFLD in patients without diabetes. Ninety-eight patients were recruited and underwent: a 2-hour OGTT with measurements of insulin every 30 min, and a liver magnetic resonance spectroscopy (1H-MRS) to measure liver fat and diagnose NAFLD. A mass spectrometry method was used to measure intact molecules of insulin. A total of 62 patients had NAFLD (48±11 yr, 66% male, BMI: 34.4±4.6kg/m2, A1c: 5.8±0.4%); and 36 did not have NAFLD (52±12 yr, 56% male, BMI: 30.5±6.8kg/m2, A1c: 5.5±0.4%). Fasting insulin levels were higher in NAFLD patients (17±10 vs. 7±3 μU/ml, p<0.001), but showed similar excursions during the OGTT (120 min incremental AUC: 7.4 [4.4-14.5] vs. 5.7 [4.2-8.9], p=0.22). Fasting intact insulin measurements had an AUROC of 0.90 (0.84-0.96) to predict NAFLD. This was significantly better than measuring insulin by radioimmunoassay (RIA) (AUC 0.80 [0.71-0.89], p=0.007). Using a cut-off of 10.5 μU/ml, we observed a sensitivity, specificity, PPV, and NPV of 92% (87-98%), 71% (62-80%), 79% (71-87%), and 89% (83-95%), respectively. Intact fasting insulin was better than other clinical variables (e.g., ALT, AST, triglycerides, HDL, glucose, A1c, and BMI) to predict NAFLD. When combined with ALT (intact insulin x ALT), it detected NAFLD with AUC 0.94 (0.89-0.99) and PPV and NPV of 93 and 88%, respectively. This newly described approach was significantly better than previously validated non-invasive scores such as NAFLD-LFS (p=0.009), HIS (p<0.001) and TyG index (p=0.039).

Conclusions: In patients without diabetes, accurate measurement of fasting intact insulin levels by mass spectrometry constitutes an easy and non-invasive strategy to predict presence of NAFLD.

Disclosure

F. Bril: None. M. J. Mcphaul: Employee; Self; Quest Diagnostics. S. Kalavalapalli: None. R. Lomonaco: None. D. Barb: None. E. Godinez: None. K. Cusi: None.

Funding

The Obesity Society; University of Florida

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