LAUSR

Abstract Background: The leading cause of death in US women is cardiovascular disease (CVD). Obesity and type-2 diabetes (T2D) are independent risk factors for cardiovascular disease while obesity is the leading risk factor for T2D. CDC reports that 53% of African American women are obese, compared to 32% of European American women. They also suggest that the prevalence of obesity may contribute to the increase in prevalence of diabetes; 85.2% of people with T2D are overweight or obese. The CDC estimates that 1 in 3 Americans will have diabetes by 2050, if this trend continues. Obesity, diabetes, and CVD are all associated with inflammation created by the expansion of adipose tissue. Low grade inflammation is associated with insulin resistance and precedes the onset of T2D in adults. Methods: A total of 30 serum samples were collected from African American women: 15 obese, normal HbA1c and 15 obese, high HbA1c. Clinical metabolic parameters were determined using standard commercial kits administered by Laboratory Corporation of America. Thirty chemokines/cytokines were measured using 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 correlation between cytokine expression and clinical metabolic parameters. Results: Serum levels of IL-3 (P=0.007), IL-4 (P=0.02), IL-7 (P=0.002), TNF-α (P=0.006), IFN-α2 (P=0.001) and CX3CL1 (P=0.02) were significantly higher in obese, African American women with elevated HbA1c. IL-7 (R=0.53, P=0.01) and TNF-α (R=0.37, P=0.04) were positively correlated with HbA1c in all patients. In patients with elevated HbA1c, IL-3 (R=-0.72, P=0.005) and IFN-α2 (R=-0.83, P=0.05) were negatively correlated with HbA1c. Several clinical metabolic parameters were also correlated with cytokines. TNF- α (R=0.48, P=0.008), IL-7 (R=0.58, P=0.005), CX3CL1 (R=0.50, P=0.006) and IFN- α2 (R=0.42, P=0.03) were positively correlated with triglycerides in all patients. TNF- α (R=0.49, P=0.007), IL-7 (R=0.58, P=0.005), CX3CL1 (R=0.50, P=0.006) and IFN- α2 (R=0.42, P=0.03) were positively correlated with VLDL in all patients. In patients with elevated HbA1c, IL-7 (R=-0.65, P=0.03) and IFN- α2 (R=-0.57, P=0.04) were negatively correlated with HDL. IL-7 (R=-0.58, P=0.005) was negatively correlated with HDL in all patients. Conclusions: Increased cytokine expression of IL-3, IL-4, IL-7, TNF- α, IFN- α2, and CX3CL1 is associated with T2D in obese, African American women. Circulating cytokine expression is associated with increased cardio-metabolic disease risk. Our observations provide insights into T2D and propose new avenues for therapeutic strategies to combat obesity and its associated metabolic abnormalities.