On the fringe of understanding the diabetes disease paradox: A multidisciplinary approach in combining clinical practice and immunology

Background: Type 2 Diabetes (T2D) is a growing epidemic in the United States and around the world. Despite evidence in support of lowering hemoglobin A1c (A1c) to 7% or less, some studies have found that T2D patients who achieve these levels still experience adverse outcomes. We evaluate B lymphocyte production of proinflammatory chemokine interleukin 8 (IL-8) in order to profile T2D patients. Methods: B cells were isolated from whole blood samples of T2D patients (N=48) and IL-8 (basal and stimulated) production was measured. Subjects were grouped by basal IL-8; high (Group 1), intermediate (Group 2), and no response (Group 3). Clinical data was obtained and used to complete the Diabetes Severity Index (DSI). Estimates for odds ratios and 95% confidence intervals were obtained using logistic regression. Results: Clinically, Group 1 had the lowest A1c (median =7.7%) and highest DSI (mean=7.4). Immunologically, Group 1 had the highest mean basal and stimulated IL-8 levels (p< 0.001 and p< 0.03, respectively). Group 1 had 1.23 times the odds of having renal disease and 1.06 times the odds of having cardiovascular disease compared to other groups (95% CI: (0.202, 7.506) and (0.285, 3.924)). Conclusion: The findings profile a unique subgroup of T2D patients by IL-8 levels. T2D patients with the highest IL-8 production may be at higher risk for adverse outcomes despite having the lowest A1c. The data suggests IL-8 production and DSI score can help profile T2D patients by characterizing additional risks that may be overlooked when using parameters like A1c.