P-0566-Association of hyperleptinemia with insulin resistance in different grades of fatty liver among prediabetic subjects
Author block: I.A. Hossain, L. Ali
Biochemistry and Cell Biology, Bangladesh University of Health Sciences (BUHS), Dhaka, Bangladesh.
Background: Nonalcoholic fatty liver disease (NAFLD) is emerging as a major health problem in Bangladeshi population and prediabetic subjects are more vulnerable to it due to the defect of insulin resistance in both the conditions. The determinants of the insulin resistance, however, are still unclear in this population. 
Aims: In the present study, the association of elevated levels serum leptin, an important determinant of insulin sensitivity, has been studied in different grades of fatty liver among a group of Bangladeshi prediabetic subjects.
Methods: Under a cross-sectional analytical design a total of 160 prediabetic subjects (M/F, 88/72; age in years, 45.20±9.43; BMI in kg/m2, 26.25±4.63; M±SD) comprising 59 impaired fasting glucose (IFG) (37/22; 48.68±8.88; 26.91±5.70), 43 impaired glucose tolerance (IGT) (16/27; 40.49±9.42; 25.75±3.75) and 58 IFG-IGT subjects (35/23; 45.16±8.55; 25.95±3.94) were investigated. Diabetes and prediabetes were diagnosed by 2-sample OGTT based on WHO Study Group criteria. NAFLD was confirmed on the basis of ultrasound assessment of the liver and the subjects were divided into an NAFLD group (n=73; 38/36; 45.85±9.18; 28.13±4.64) and a non-NAFLD group (n=86; 50/36; 44.64±9.66; 24.64±3.98). Fatty liver severity was classified into grade 0 (normal echogenicity, n=86), grade 1 (mild steatosis, n=48) and grade 2 (moderate steatosis, n=26). Serum glucose was measured by the glucose-oxidase method. Serum insulin and leptin were measured by ELISA techniques. Insulin resistance was measured by homeostasis model assessment (HOMA-IR). Data were analyzed by univariate, bivariate and multivariate analysis as appropriate.
Results: NAFLD subjects showed significantly higher levels of logarithmically transformed serum leptin (log leptin) compared to their non-NAFLD counterparts (1.20±0.31 vs. 0.88±0.38 ng/ml, p<0.001). They also showed significantly higher levels of HOMA-IR (3.42±1.25 vs. 1.94±0.85, p<0.001). Log leptin and HOMA-IR levels increased with increasing severity of NAFLD and their levels were significantly higher in grade 1 (1.18±0.32 and 3.51±1.25, p<0.001) and grade 2 (1.25±0.31 and 3.25±1.26, p<0.001) compared to the grade 0 (0.88±0.38 and 1.94±0.85) NAFLD subjects. On Pearson’s correlation analysis, HOMA-IR showed significant positive correlation with log leptin in grade 1 (r=0.355, p=0.013) and grade 2 (r=0.348, p=0.044) NAFLD subjects. On multiple linear regression analysis, HOMA-IR showed significant positive association with log leptin in grade 1 (β=0.357, p=0.015) and grade 2 (β=0.330, p=0.042) NAFLD subjects after adjusting the effects of potential confounders of waist to hip ratio (WHR), percent body fat (%BF) and triglyceride (TG) respectively. On binary logistic regression analysis, HOMA-IR and log leptin were found to be significant determinants of NAFLD state [HOMA-IR, Odds ratio (OR)=3.222, 95% confidence interval (CI):2.083-4.983, p<0.001 and log leptin, OR=1.056, 95% CI: 1.013-1.102, p=0.011] after adjusting the effects of WHR, %BF and TG respectively. 
Conclusion: Hyperleptinemia seem to have an association with different grades of NAFLD among Bangladeshi prediabetic individuals and this association is mediated by insulin resistance during this disorder.