A-073 Is there a relationship of FIB 4 with weight and insulin resistance in subjects without type 2 diabetes and with normal transaminases?
Authors: Correa Wengerkievicz Lopes A , Fragoso Perozo A F , Fontes R , Serfaty F , Castelo M C , Cunha M R , Schrank Y , Gomes D M , Pinheiro M M , Sabino C O , Crestani A M , Santos B S , Hirose C K , Fritsch M 
Published: October 2024

Abstract

Background
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common hepatic disease, affecting 20-30% of the world's population, and is more frequent in subjects with cardiometabolic diseases. The Fibrosis-4 Index (FIB-4) is a non-invasive scoring system that helps estimate the risk of hepatic fibrosis in MASLD. It is based on age, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and platelets (PLT). MASLD is associated with high risk of insulin resistance (IR) and type 2 diabetes (DM2), and subjects with overweight or obesity are more likely to have both. In such cases the association of FIB-4 with IR and weight are evident. It is questioned whether, even in subjects without DM2 and with normal transaminases, FIB-4 could be associated with the body mass index (BMI) and the homeostasis model assessment of insulin resistance index HOMA-IR, which is the index usually used to assess IR. The objective of this study was to evaluate how FIB-4 would behave in subjects without DM2 and with normal transaminases and whether there was a correlation between FIB-4 with HOMA-IR and BMI in these subjects.

Methods
Authors studied the distribution of FIB-4 results and correlation of HOMA-IR and BMI with FIB-4 using the database of a clinical laboratory. We included patients aged 20-65 years, both gender, who measured fasting glucose and insulin, in the same visit, and transaminases and platelets within up to one year before or later. Were excluded hospitalized subjects, those using medications to treat DM2, dyslipidemia, subjects with blood glucose over 200 mg/dL, and AST and/or ALT above the reference range for gender and age. The methods and reference intervals were: transaminases: UVKinetic, AST &lt; 40 U/L for men and &lt; 32 U/L for women, ALT &lt; 41 for men and &lt; 33 for women; PLT: automated method, 150000-450000/µL. Glucose: hexokinase, 70 - 99 mg/dL; Insulin: electrochemiluminescence, 2-12 mcU/mL. HOMA-IR index was calculated using the equation: glucose (mg/dL) x insulin (mcIU/mL) / 405 and FIB-4 using the equation: age (years) × TGO (U/L) / [(platelets (µL) ÷1000) x √TGP (U/L))]. Shapiro Wilk test was performed to assess whether the analytes had normal distribution. To evaluate the correlation with HOMA-IR, Spearman's non-parametric correlation test was used.

Results
After applying the exclusion criteria and subtracting outliers 270,135 records were selected, 75% female, with 39,9 ± 10.1 years. As the parameters did not present Gaussian distribution, the results are shown in median and 25th and 75th percentiles: AST=18.9 (16-22); ALT=17.2 (13-23.3); PLT=266000 (229000-308000); glucose = 89.3 (84.2-95); insulin = 8.17 (5.52-12.8); HOMA-IR=1.81 (1.19-2.75); IMC=26.53 (23.80-29.91); FIB-4 = 0.65 (0.5 - 0.86). A weak and surprisingly negative correlation between HOMA-IR and BMI with FIB-4 was found. (HOMA-IR: r=- 0.2, p&lt;0.001; BMI: r=- 0.1, p&lt;0.01).

Conclusions
Our study showed that in a population with normal transaminases, FIB-4 had results compatible with low risk of fibrosis in subjects without DM2 even in cases with high HOMA-IR or BMI. The negative correlation was surprising and perhaps indicates that FIB-4 may not be a good predictor of liver fibrosis for this population profile.