PSUN300 The sex-specific correlation of IL7, high HbA1c and liver damage markers in African Americans

Abstract

Abstract Background Type 2 Diabetes (T2D) has been considered an inflammatory disease that correlates with elevated responses cytokines. The increasing prevalence of T2D worldwide, is accompanied by the higher incidence of T2D globally and nationally. African Americans (AA) compared to other ethnic groups, have a higher prevalence of obesity (49.6%) and 1.4-2.3-fold higher in T2D. IL-7 is resident to the liver and been previously reported to drive inflammation in several chronic (rheumatic) inflammatory autoimmune responses. Obese patients with high levels of HbA1c are at higher risk of inflammatory diseases compared with non- obese individuals. This suggests that high blood sugar levels and subsequent inflammation may impact the prevalence of circulating cholesterol levels of LDL and or HDL. PCSK9 regulates the LDL-receptor and could potentially be a link between inflammation and active PCSK9. Preliminary data in our lab show elevated levels of IL-7 (>8 pg/mL) significantly correlate with various serum biomarkers of lipid metabolism, inflammation, and liver damage Methods A total of 239 serum samples were collected from AA: 172 women and 67 men. All participants had an BMI > 30. This group consists of 68 normal HbA1c and 171 high HbA1c participants. Clinical metabolic parameters were determined using standard commercial kits. Cytokines were measured using Luminex X-MAP® technology. Cytokine levels were compared using unpaired t-test, followed by Pearson's correlation coefficient (r) to determine the correlation between cytokine expression and clinical metabolic parameters. Results We found that men with high HbA1c significantly correlate with BMI (P= 0.0052) and increased levels of IL-7, which was not seen in women. Women with both normal and high HbA1c levels significantly correlate with IL-7 and liver damage markers AST; normal HbA1c (P= 0.0036), high HbA1c (P= 0.0194) and ALT; high HbA1c (P=0.0174). These correlations are not seen in men supporting the possible influence of blood sugar levels on liver function in women. When normal HbA1c and high HbA1c participants are combined, all women IL-7 levels significantly correlate with active PCSK9 (P= 0.02). This suggests high circulating LDL contribute to active PCSK9, which is not present in men. Conclusion Our findings suggest increased circulating levels of IL-7 based on individuals HbA1c significantly correlate with markers of inflammation, lipid metabolism and liver damage of obese individuals with T2D, while identifying a definitive difference between men and women. These findings establish IL-7 as playing a role in inflammatory responses in obese AA with T2D and potentially being a mediator of obesity-associated inflammation. IL-7 is an indicator of sex being a variable that influences innate and adaptive immune responses, resulting in sex-specific outcomes from multiple diseases including T2D. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.