PSUN317 IL-3 is associated with HbA1c and Serum Lipids in African Americans

BACKGROUND: Obesity is highly correlated to the development of several metabolic diseases such as type 2 diabetes (T2D). Individuals with accumulated visceral adipose tissue (VAT), have increased risk of developing insulin resistance or metabolic syndrome. Studies have shown the crucial role of VAT in obesity-induced inflammation. This condition precedes the development of T2D and NAFLD. Increased levels of cholesterol are associated with obesity, cardiovascular disease (CVD) and atherosclerosis. Immune responses to these conditions are mediated by chemokines, which lead to the innate immune response characterized by the production of cytokines. IL-3 is a glycoprotein involved in inflammatory stimulation. Previously, IL-3 has been reported as ambiguous in metabolic disease. Further studies are needed to determine the role of IL-3 in T2D and cholesterol metabolism. METHODS: A total of 161 serum samples were collected from African Americans: 161 women and 71 men. Most participants had a BMI > 30 (n=171). This group consists of 95 normal HbA1c and 106 high HbA1c participants. Clinical metabolic parameters were determined using standard commercial kits. Cytokines were measured using multiplexing assays from Luminex X-MAP® technology. Cytokine levels between the two groups 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 a difference in serum IL-3 levels due to high glucose in males (P=0.03) and females (P=0.0007). In women, IL-3 levels were upregulated 1.7-fold in the presence of high circulating glucose. In men, IL-3 levels were downregulated 1.5-fold. Individuals with normal HbA1c exhibit a negative correlation between IL-3 and BMI in women (R=-0.41, P=0.02) while all men approach significance (R= -0.27, P=0.07). All women have a positive correlation between IL-3 and HDL (R=0.23, P=0.03), which approaches significance in women with high HbA1c (R=0.28, P=0.06) but is lost in all men and all women. IL-3 is also negatively correlated with Triglycerides in women with high HbA1c (R=-0.28, P=0.05) and is positively correlated in men with normal HbA1c (R=0.56, P=0.05). CONCLUSION: An increase in obesity increases the expression of pro-inflammatory cytokines and risk of metabolic disease. The role of IL-3 has been previously described as ambiguous, in part due to a lack of associations with clinical serum parameters of metabolic disease. IL-3 may be anti-inflammatory and lose its protective role while blood sugar remains elevated. This is consistent with the decrease in serum IL-3 levels as BMI increases. A high BMI may contribute to a cascade of pro-inflammatory cytokines that IL-3 is unable to suppress. IL-3 is also correlated with lipids and cholesterols known to cause CVD and atherosclerosis. This suggests that IL-3 may regulate cholesterol and lipid management in T2D. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.