Soluble TNF Receptor and Periodontal Disease in Non-obese Japanese Type 2 Diabetic Patients

The major clinical consequence of type 2 diabetes is mortality and morbidity from atherosclerotic vascular disease. Although it remains to be clarified whether which factors are responsible for the evolution of atherosclerosis, tumor necrosis factor (TNF) seems to account for the development of atherosclerosis [1] [2] [3]. We recently demonstrated that TNF receptors are not only associated with albuminuria but also with brachial-ankle pulse wave velocity in non-obese Japanese type 2 diabetic patients [1] [2]. Elevated soluble TNF receptor levels have recently been shown to be predictive of cardiovascular mortality in patients with chronic heart failure [3]. Longitudinal study shown by Shai et al. [4] disclosed the importance of TNF receptor in the risk of atherosclerosis in type 2 diabetic patients.

On the other hand, periodontal disease, a low-grade inflammation, per se is likely to be associated with atherosclerosis. We demonstrated that periodontal disease is associated with albuminuria or carotid atherosclerosis in Japanese type 2 diabetic patients [5] [6]. Sareni et al. [7] reported similar results indicating that periodontal disease is a strong predictor of mortality from ischemic heart disease and diabetic nephropathy in type 2 diabetic patients. To the best of our knowledge, however, the relationships between periodontal disease and TNF system activity including TNF receptors were not yet investigated in type 2 diabetic patients. In this regard, the major problem is that insulin therapy or the degree of overweight per se affects TNF concentration and periodontal disease. We therefore recruited non-obese Japanese insulin-naïve type 2 diabetic patients and investigated the relationships between TNF system activity and periodontal disease.

Fifty-one insulin-naïve type 2 diabetic patients were enrolled. Their body mass index (BMI) and glycosylated hemoglobin (HbA1c) were 23.6±1.5 kg/m² (mean±SEM) and 7.9±1.7%, respectively. Along with TNF-α, soluble TNF receptor 1 (sTNF-R1) and sTNF-R2 were measured. The degree of periodontal disease was evaluated with the probing depth of periodontal pocket.

Univariate analysis showed that mean depth of periodontal pocket was positively correlated with sTNF-R1 (r=0.440, P<0.01) and sTNF-R2 (r=0.332, P<0.05). TNF-α, however, was not associated with the depth. No significant relationship was observed between BMI, HbA1c, and TNF-α or the depth of periodontal pocket. Multiple regression analyses revealed that the depth of periodontal pocket was independently predicted by sTNF-R1 (F=16.6, P<0.0002), which explained 25.3% of the variability in the depth of periodontal pocket.

From these results, it can be hypothesized that abnormal TNF system activity observed in diabetic patients may in part be associated with the severity of periodontal disease and that this finding might explain why periodontal disease is associated with atherosclerosis in type 2 diabetic patients.

References

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