Intact Fasting Insulin Identifies Nonalcoholic Fatty Liver Disease in Patients Without Diabetes

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.

Assessing strategies to target screening for advanced liver fibrosis among overweight and obese patients

“…Recently, the American Gastroenterological Association (AGA), in collaboration with members of other societies, published a NAFLD/NASH Clinical Care Pathway [8] . In this work, the authors identified three groups of patients at greatest risk of NAFLD/NASH-related fibrosis: 1) patients with T2D, 2) patients with two or more metabolic risk factors, and 3) patients with incidental findings of hepatic steatosis or elevated aminotransferases.…”

“…Therefore, it seems intuitive including other 'at risk' groups in the guidelines, such as patients with diabetes and those with metabolic risk factors. However, these and other guidelines [4,8,18] recommend initiating the screening for advanced liver fibrosis with non-invasive tests, which rely heavily on plasma aminotransferase elevations, so patients with normal plasma aminotransferases may still go undiagnosed with these tools. Therefore, adding more 'at risk' groups may not provide an advantage over just selecting patients based on elevated plasma aminotransferases.…”

“…As vibration-controlled transient elastography (VCTE) or Fibroscan® becomes more widely available, it is likely that it will be increasingly used to diagnose advanced fibrosis in NAFLD [19] . Moreover, it has been proposed as a second step in the diagnostic algorithm by recent guidelines [8] . However, because it is still not widely available, especially in developing countries, it was important to establish the most effective way to screen for advanced fibrosis using only simple, cheap, and widely available tools.…”

“…They have been widely used to predict the presence of NAFLD, NASH, and/or advanced fibrosis. Moreover, national and international guidelines have even endorsed some of these approaches [4,7,8] . However, a clear consensus regarding which patients would benefit the most from advanced fibrosis screening is lacking.…”

“…In which case, the best strategy to select these high-risk patients is currently unknown. While different approaches have been proposed (i.e., selecting patients based on the presence of diabetes, presence of metabolic syndrome, elevated plasma aminotransferases, or presence of hepatic steatosis) [8] , no prior study has compared these approaches head-to-head. Therefore, the aim of this study is to compare different strategies to target screening for advanced liver fibrosis in overweight and obese patients.…”