ECE2018 Guided Posters Diabetes Epidemiology (11 abstracts)
1Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athenseece, Athens, Greece; 2Endocrine Unit, 1st Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 3Iaso Maternity Hospital, Athens, Greece; 4Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 5Medical School, University of Crete, Heraklion, Crete, Greece; 6Diabetologic Center, First Department of Propedeutic Medicine, Laiko University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; 7First Department of Psychiatry, Eginitio Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Objective: Neuroinflammation is a common primary or secondary mediator of the neurodegenerative process accompanying Alzheimers disease (AD). Impaired brain insulin signaling, defining brain insulin resistance may represent a link between AD and type 2 diabetes mellitus (T2DM) while neuronal apoptosis may also be involved in the inflammatory process. Peripheral cytokine levels of IL-1β, IL-6, TNFα along with high sensitivity C-reactive protein (hsCRP) and apoptotic marker Fas ligand (FasL) were investigated in AD patients and they were compared with T1DM, T2DM.
Methods: We studied 93 patients: 41 with AD, 20 T1DM, 21 patients with T2DM and 11 healthy subjects. The number of cytokine-secreting peripheral blood mononuclear cells (nPBMCs) before and after mitogenic stimulation was determined for interleukin-1β (nIL-1β), interleukin-6 (nIL-6) and tumor necrosis factor-α (nTNFα) by the Enzyme-Linked-Immuno-spot assay. Serum levels of hsCRP and Fas ligand (FasL) were determined by ELISA.
Results: The studied subgroups did not differ in gender but differed in age. hsCRP had higher levels in AD (statistically significant difference only compared to T1DM, P=0.02) and lower in controls. The nPBMCs was higher in AD patients after stimulation than in basal conditions. This increase showed a statistically significant increase in nTNFα (P<0.001 versus T2DM, P<0.001 vs. T1DM, P=0.005 vs. control) and nIL-6 (P=0.039 vs. T2DM, P<0.001 vs. T1DM, P=0.003 vs. control) after stimulation with PMA, in all studied groups, but in basal conditions only nTNFα was higher in AD (P=0.011 versus control, P=0.02 versus T1DM). FasL concentrations in AD subgroup displayed statistically higher levels compared to all the other subgroups (P<0.001 versus T2DM, P<0.001 versus T1DM, P<0.001 versus control), while T2DM and T1DM subgroups had statistically lower levels compared to controls (P<0.001 and P=0.035, respectively) and T2DM had statistically lower levels compared to T1DM (P<0.001) (P=0.08). The nPBMCs was positively correlated with plasma levels of Fas-L after correction with age and this correlation was seen in AD subgroup only.
Conclusion: Low-grade systemic inflammation is higher in patients with AD compared to diabetic patients particularly after mitogenic stimulation. The Fas-FasL pathway, displaying the highest levels in AD and the lower in diabetes compared to control subjects, may have a role in this process as it is extrapolated by the positive correlation of FasL concentration and the magnitude of inflammatory response particularly in AD. Further investigation in the inflammatory-apoptotic pathway will shed light to any druggable pathway of ill-controllable AD.