| Diabetes is a major risk factor for severe periodontitis (PD) and coronary heart disease (CHD). Each of these conditions displays enhanced systemic and local inflammatory responses. These studies represent a culmination of investigations that examined the potentiating effects of PD on hyperglycemia and CHD and the effects of hyperglycemia on monocytic inflammatory responses. As a component of the Dental Atherosclerosis Risks in Communities (Dental ARIC) study, cross-sectional analyses were performed to determine the relationship between PD status, CHD, and diabetes. We determined that PD is associated with impaired fasting glucose suggesting that PD may contribute to the metabolic dysregulation in glucose metabolism. Diabetes is a risk factor for CHD, as determined by B-mode ultrasound measures of intimal-medial wall thickness (IMT) and acoustic shadowing of plaques. Our data suggest that PD is associated with thicker IMT and acoustic shadowing, independent of diabetic status. In addition, we hypothesized that hyper-inflammatory processes are secondary to the chronic effects of hyperglycemia and the formation of biologically active advanced glycation endproducts (AGES). Using AGE-BSA as a stimulant, we examined the monocytic inflammatory response and the kinetics of NF-kappaB activation subsequent to bacterial LPS challenge. AGE pretreatment and LPS challenge resulted in a IkappaB kinase (IKK)-dependent increase in Cox-2 gene expression suggesting that diabetes and AGE formation along with LPS exposure may promote an NF-kappaB-mediated hyper-inflammatory state. Collectively this work provides insight to a molecular mechanism that supports the epidemiologic association between PD, hyperglycemia, inflammation and CHID. |
