Association of subclinical inflamation and insulin resistance with non alcoholic fatty liver disease in prediabetic subjects

Abstract

Background: Prediabetes, inflammation and type 2 diabetes mellitus (T2DM) are believed to be associated with a worse metabolic profile in patients with nonalcoholic fatty liver disease (NAFLD). The pathophysiology involved in the development and progression of NAFLD is associated with insulin resistance and inflammation. Nevertheless, the association of subclinical inflammation and insulin resistance with NAFLD has not been studied among the Bangladeshi prediabetic subjects. Objectives: The aim of the study was to explore the proportion of prediabetic subjects with NAFLD and to investigate whether this association is mediated by suclinical chronic inflammation and insulin resistance. Design and Methods: Under a cross-sectional analytical design a total of 110 (Mean±SD age, 45±9 years) consecutive subjects were recruited. NAFLD was diagnosed on the basis of ultrasound assessment of the liver and were divided into a NAFLD group (n=48) and a non NAFLD group (n=62). All individuals underwent anthropometric and medical examinations. Among laboratory investigations, insulin secretory function (HOMA% B) and insulin sensitivity (HOMA% S) was calculated from fasting blood glucose and fasting serum insulin (pmol/l) values by Homeostasis Model Assessment (HOMA) using HOMA-CIGMA software. Fatty Liver Index, a recently identified correlate of NAFLD, was also estimated. Serum glucose was measured by glucose-oxidase mehod; lipid profile & liver enzymes were measured by enzyme colorimetric method, hs-CRP & insulin by enzyme immunoassay. Results: Forty four percent (n=48, 58.3 % of the men, 41.7 % of the women) of the study subjects had NAFLD consisting 29 (60%) IGT, 13 (27 %) IFG & 6 (13 %) IFG-IGT and 56% (n=62, 56.5 % of the men, 43.5 % of the women) of the study subjects had non NAFLD consisting 36 (58%) IGT, 21 (34%) IFG & 4 (8%) IFG-IGT. The prevalence of NAFLD was 44% among the prediabetes. Study subjects were age & BMI matched. WHR, percent body fat (%BF) and blood pressure (SBP & DBP) were significantly higher in NAFLD group compared to non NAFLD group (0.95±0.48 vs. 0.93±0.04, p=0.048), (32±8 vs. 28±6, p=0.021) and [134±34 vs. 112±15 & 93±26 vs. 76±17, (mmHg) p<0.001] respectively. Among the glycemic status, HbA1c was significantly higher in NAFLD group compared to non NAFLD group [5.8±0.4 vs. 5.3±0.5, (%) p<0.001]. Among lipidemic profile, serum cholesterol & triglycerides were significantly higher in NAFLD group compared to non NAFLD group [198±44 vs. 182±38 (mg/dl), p=0.05) & (201±136 vs. 153±81 (mg/dl), p=0.04] whereas; HDL-c was significantly lower [34±74 vs. 38±7 (mg/dl), p=0.007] in NAFLD group compared to non NAFLD group. Among liver enzymes, SGPT, SGOT & SGGT were significantly higher in NAFLD group compared to non NAFLD group [37±19 vs. 29±12 (IU/L), p=0.021], [36±21 vs. 26±8 (IU/L), p<0.001] and [34±12 vs. 24±11 (IU/L), p<0.001]. Among insulinemic status, postprandial insulin and HOMA-IR were significantly higher in NAFLD group compared to non NAFLD group [52 (11-170) vs. 35 (3-147) (µIU/ml), p=0.008] and [2.5 (0.9-6.9) vs. 1.9 (0.6-4.5), p=0.002] whereas; HOMA%S and HOMA%B were significantly lower in NAFLD group compared to non NAFLD group [43 (15-80) vs. 57 (22-164), p=0.002] and [110 (9-198) vs. 127 (52-198), p=0.001]. Among inflammatory status, serum hs-CRP and ESR were significantly higher in NAFLD group compared to non NAFLD group [3.7 (0.1-14.9) vs. 1.7 (0.2-13.2) (mg/l), p<0.001] and [25 (7-55) vs. 17 (5-55) (mm/hr), p=0.026]. On Spearman’s correlation analysis fasting insulin, HOMA%B, & HOMA-IR showed significant positive correlation with BMI (r=0.573, p<0.001 & r=0.431, p= 0.003; r=0.544, p<0.001) & WC (r=0.353, p=0.024; r= 0.349, p=0.022 & r= 0.450, p=0.002 respectively) in NAFLD group. Whereas HOMA%B showed significant negative correlation with FBS (r=-0.367, p=0.018) in NAFLD subjects. Whereas hs-CRP showed significant positive correlation with BMI (r=0.459, p=0.003) and WC (r=0.339, p=0.035) while, it showed significant negative correlation with WHR (r=-0.334, p=0.038) in NAFLD group. Using binary logistic regression analysis, it was found that hs-CRP is a significant determinant of NAFLD [hs-CRP OR (95% CI): 1.2 (1.03-1.55), p=0.025] after adjustment of major confounders (age, BMI and sex). Moreover, in a different model HOMA-IR, HOMA%B and HOMA%S were also found to be significant determinants of NAFLD [HOMA-IR OR (95% CI): 2.44 (1.213-4.913), p=0.012], HOMA%B OR (95% CI): 0.95 (0.93-0.98), p=0.001] and [HOMA%S OR (95% CI): 0.92 (0.88-0.97), p=0.002] after adjustment of major confounders (age, BMI and sex). Conclusions: From the present data it may concluded that a high proportion (more than one-third) of the prediabetic subjects have NAFLD and the distribution of the disorder is almost similar in various subgroups of prediabetes. Subclinical chronic inflammation and insulin resistance seem to be independent mediators of the association between NAFLD and prediabetes. The data also indicate that the inflammatory condition and insulin resistance are associated with each other and those in turn are affected by central obesity and dyslipidemia in prediabetic subjects.