PGE 2 , IL‐1 β, and TNF‐α Responses in Diabetics as Modifiers of Periodontal Disease Expression

Abstract

Diabetes mellitus is a systemic disease that affects more than 12 million people in the United States and represents a risk factor for periodontitis with odds ratios of 2.1 to 3.0. New data support the concept that in diabetes‐associated periodontitis, the altered host inflammatory response plays a critical role. We have recently examined the gingival crevicular fluid (GCF) mediator level, monocytic secretion, and clinical presentation of 39 insulin‐dependent diabetes mellitus (IDDM) patients and 64 non‐diabetic patients with various degrees of periodontal health and disease. First, we found that there was an unexpected high level of GCF mediators among the IDDM subjects, even in the gingivitis and mild periodontitis patients. Furthermore, the GCF and monocytic mediator responses were obviously bimodal in distribution with respect to periodontal status. Gingivitis patients and mild periodontitis patients represented one low response group, and the moderate and severe periodontitis subjects the high response group. Accordingly, these 4 periodontal subgroups were pooled to form 2 main groups for analyses— group A (AAP Types I–II) and group B (AAP Types III–IV). Diabetics had significantly higher GCF levels of both PGE 2 and IL‐1β when compared to non‐diabetic controls with similar periodontal status. Within the diabetic group, the GCF levels of these inflammatory mediators were almost 2‐fold higher in group B subjects when compared to diabetics from group A. Among diabetics, GCF TNF‐α levels were only marginally detectable and no significant difference was found between group A and group B patients. Insulin‐dependent diabetic patients with gingivitis or mild periodontitis (group A) and moderate to severe periodontitis (group B) have abnormal monocytic inflammatory secretion in response to LPS challenge from Porphyromonas gingivalis (P. gingivalis) as compared to non‐diabetic periodontal patients. Data suggest that the diabetic state results in a significantly upregulated monocytic secretion of PGE 2 (4.2‐fold), IL‐1β (4.4‐fold), and TNF‐α (4.6‐fold) when compared to non‐diabetic controls. Within diabetics, LPS dose‐response curves demonstrated that monocytes from group B patients secreted approximately 3 times more PGE 2 and 6.2 times more TNF‐α than those from group A; however, there was no significant difference in monocytic IL‐1β secretion between the 2 diabetic groups. This upregulated monocytic trait is thought to exist independently of the presence of severe periodontal disease since, in non‐diabetic patients with adult periodontitis, Gram‐negative bacterial infections alone are not sufficient to elicit a systemic hyperresponsive monocytic trait. Between group A and group B diabetics, there was no significant difference in metabolic control as expressed by mean level of glycosylated hemoglobin (HbA 1c ). In conclusion, our data suggest that diabetic patients have exaggerated inflammatory responses when compared to non‐diabetic controls. Furthermore, within diabetics, individuals with moderate to severe periodontitis (group B) have significantly elevated monocytic secretion of PGE 2 and TNF‐α upon LPS challenge and significantly higher GCF levels of PGE 2 and IL‐1β when compared to patients with gingivitis or mild periodontal disease (group A). Thus, we suggest that insulin‐dependent diabetes mellitus is a significant risk factor for more severe periodontal disease because, as compared to non‐diabetics, diabetic subjects react with an abnormally high degree of inflammation to an equivalent bacterial burden . Ann Periodontol 1998;3:40–50.