The Journal of Clinical Endocrinology and Metabolism Journal Article

Intact Insulin in NAFLD

November 30, 2021
 

Fernando Bril, Michael J McPhaul, Srilaxmi Kalavalapalli, Romina Lomonaco, Diana Barb, Meagan E Gray, Dov Shiffman, Charles M Rowland, Kenneth Cusi
The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 11, November 2021, Pages e4360–e4371
https://doi.org/10.1210/clinem/dgab417

Abstract

Context

Patients with nonalcoholic fatty liver disease (NAFLD) are characterized by insulin resistance and hyperinsulinism. However, insulin resistance measurements have not been shown to be good diagnostic tools to predict NAFLD in prior studies.

Objective

We aimed to assess a newly validated method to measure intact molecules of insulin by mass spectrometry to predict NAFLD.

Methods

Patients underwent a 2-hour oral glucose tolerance test (OGTT), a liver magnetic resonance spectroscopy (1H-MRS), and a percutaneous liver biopsy if they had a diagnosis of NAFLD. Mass spectrometry was used to measure intact molecules of insulin and C-peptide.

Results

A total of 180 patients were recruited (67% male; 52 ± 11 years of age; body mass index [BMI] 33.2 ± 5.7 kg/m2; 46% with diabetes and 65% with NAFLD). Intact fasting insulin was higher in patients with NAFLD, irrespective of diabetes status. Patients with NAFLD without diabetes showed ∼4-fold increase in insulin secretion during the OGTT compared with all other subgroups (P = 0.008). Fasting intact insulin measurements predicted NAFLD in patients without diabetes (area under the receiver operating characteristic curve [AUC] of 0.90 [0.84–0.96]). This was significantly better than measuring insulin by radioimmunoassay (AUC 0.80 [0.71–0.89]; P = 0.007). Intact fasting insulin was better than other clinical variables (eg, aspartate transaminase, triglycerides, high-density lipoprotein, glucose, HbA1c, and BMI) to predict NAFLD. When combined with alanine transaminase (ALT) (intact insulin × ALT), it detected NAFLD with AUC 0.94 (0.89-0.99) and positive and negative predictive values of 93% and 88%, respectively. This newly described approach was significantly better than previously validated noninvasive scores such as NAFLD-LFS (P = 0.009), HSI (P < 0.001), and TyG index (P = 0.039).

Conclusion

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

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