Abstract Disclosure: F. Bril: None. J. Louie: Employee; Self; Quest Diagnostics. D. Shiffman: Consulting Fee; Self; Quest Diagnostics. M.J. McPhaul: Employee; Self; Quest Diagnostics. Stock Owner; Self; Quest Diagnostics. The increasing prevalence of obesity in the US and worldwide has fueled a dramatic increase in the number of patients affected with nonalcoholic fatty liver disease (NAFLD). NAFLD is the deposition of excess fat in hepatocytes and is associated with increased insulin resistance. Unfortunately, there is a widespread belief that NAFLD is the liver manifestation of the metabolic syndrome (MetS). The aim of the study was to determine whether NAFLD can exist in the absence of the typical metabolic abnormalities that define MetS (i.e., obesity, hyperglycemia, dyslipidemia), and whether patients with NAFLD and without metabolic abnormalities would be missed if NAFLD scores based on adiposity, dyslipidemia or glycemia are used. Methods: We studied employees and spouses who participated in an annual wellness program that includes laboratory tests and anthropometric measurements. To assess the proportion of individuals likely to be affected with NAFLD we used the product of fasting intact insulin (II) and alanine transaminase (ALT) levels (II*ALT), a measure highly correlated with liver fat as measured by magnetic resonance spectroscopy in non-diabetic individuals (Bril et al, JCEM 2021) as well as fatty liver index (FLI, a clinical score for NAFLD based on BMI, triglycerides [TG], waist circumference and gamma-glutamyl transferase [GGT]). NAFLD was defined as II*ALT ≥ 290 or FLI ≥ 60. Individuals with diabetes, BMI <18.5, and those with missing data were excluded from the analysis. Results: In total, 29,977 participants met our criteria. Of these, 9,642 (32%) had prediabetes (PreD) and 20,335 (68%) were normoglycemic (NG: normal HbA1c and normal fasting plasma glucose). In the NG population, 2,443 (12.0%) individuals were identified as likely having NAFLD using II*ALT criteria. Even among non-obese patients (<30 kg/m2) with normal TG (<150 mg/dL) and normal HDL-C (males: ≥40 mg/dL; females ≥50 mg/dL), we identified 4.1% (n =426) who were likely to have NAFLD by the II*ALT criteria. Moreover, among patients considered ‘metabolically healthy obese’ due to the absence of hyperglycemia or dyslipidemia, 17.2% were likely to have NAFLD. Of note, FLI detected a smaller percentage of patients at risk of NAFLD among non-obese patients without hyperglycemia and dyslipidemia: 223 (2.1%). Among patients with PreD, those non-obese with normal TG and HDL-C showed a prevalence of NAFLD of 12.4% based on II*ALT, and only 5.5% based on FLI. Conclusion: A substantial percentage of patients has NAFLD even in the absence of obesity, dyslipidemia, and hyperglycemia. This implies that NAFLD can exist in the absence of MetS. While longitudinal studies are needed for confirmation, it suggests that NAFLD can predate the development of these metabolic abnormalities. Therefore, diagnostic methods that do not rely in adiposity, hyperglycemia, or dyslipidemia are needed to identify these patients. Presentation: Thursday, June 15, 2023
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