Salivary and serum oxidative stress biomarkers and advanced glycation end products in periodontitis patients with or without diabetes: A cross‐sectional study

Abstract

Background Non‐invasive methods for periodontitis diagnosis would be a clinically important tool. This cross‐sectional study aimed to investigate the association between oxidative stress, glycation, and inflammation markers and periodontal clinical parameters in periodontitis and periodontally healthy patients with type 2 diabetes and corresponding systemically healthy controls. Methods Sixty‐seven periodontally healthy (DM‐H, n = 32) and periodontitis (DM‐P, n = 35) patients with type 2 diabetes, and 54 systemically healthy periodontitis (H‐P, n = 26) and periodontally healthy (H‐H, n = 28) controls were included. Clinical periodontal parameters, body mass index, fasting glucose, hemoglobin A1c (HbA1c), along with saliva and serum 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), malondialdehyde (MDA), 4‐hydroxy‐2‐nonenal (4‐HNE), advanced glycation end products (AGE), AGE receptor (RAGE) and high sensitivity C‐reactive protein (hsCRP) levels were recorded and analyzed. Results Salivary 8‐OHdG levels were significantly higher in periodontitis compared to periodontally healthy patients, regardless of systemic status (P < 0.001). Salivary MDA levels were significantly higher in all disease groups compared to H‐H group (P ≤ 0.004). Serum AGE levels were significantly higher in diabetic groups than systemically healthy groups (P < 0.001) and in H‐P compared to H‐H (P < 0.001). Bleeding on probing (BOP) and clinical attachment level (CAL) strongly correlated with salivary 8‐OHdG and serum hsCRP (P < 0.001). In systemically healthy patients, salivary 8‐OHdG was the most accurate marker to differentiate periodontitis from controls (AUC = 0.84). In diabetics salivary 4‐HNE and RAGE were the most accurate (AUC = 0.85 for both). Conclusion Salivary 8‐OHdG alone or in combination with 4‐HNE, AGE and RAGE for diabetics, and salivary 8‐OHdG alone or in combination with MDA and hsCRP for systemically healthy persons, could potentially serve as non‐invasive screening marker(s) of periodontitis.

Serum Inflammatory and Prooxidant Marker Levels in Different Periodontal Disease Stages

“…Most previous periodontal studies evaluated oxidative stress through the global burden of ROS and guanine-derived biomarkers in saliva and gingival crevicular fluid [42][43][44]. However, in this current study, we evaluated fluctuations in both markers in blood and urine; these fluctuations are more commonly related to systemic oxidative damage markers associated with periodontal diseases, such as MDA and 8-OHdG [13,18,19,[45][46][47][48].…”

“…Several epidemiological studies have reported that periodontitis is related to arteriosclerotic events, and this association has been suggested due to the increase in serum levels of proinflammatory and pro-oxidant markers in both diseases, such as TNFα, IL-1, IL-6, and CRP [26][27][28][29], fibrinogen [30], MDA [18,25], and 8-OHdG [13,31]. Recently, a study has even shown that periodontitis-especially severe-is independently associated with a considerable increase in platelet count due to an increase in the systemic inflammation, which could be a new potential link with cardiovascular disease [32].…”

“…Over the past few years, numerous clinical and basic experimental studies have shown a strong association between oxidative stress and periodontitis, but most of these periodontal studies evaluated total antioxidant capacity, total oxidant status, and oxidative stress index [12]. However, other recent studies evaluated oxidative stress markers, such as MDA and 8-OHdG levels, but mainly at the local level in saliva [13][14][15][16] and gingival crevicular fluid [14,17] and only a few studies evaluated MDA and 8-OHdG levels in serum [13,18,19]. Although these studies have different results, associations between periodontitis and MDA and 8-OHdG levels have been observed [18][19][20].…”

Pathogenic Molecular Mechanisms in Periodontitis and Peri-Implantitis: Role of Advanced Glycation End Products

“…In diabetic patients, salivary RAGE detection has been suggested as a novel biomarker of periodontal health. Serum AGE levels were reported to be elevated in systemically healthy periodontal patients compared to the non-periodontal group, shedding light on the yet not fully known correlation between periodontitis and AGEs [53]. Serum and GCF concentrations of sRAGE were reduced in patients with periodontitis and T2DM compared to those without T2DM.…”

“…On the same study, TNF-α was controversially elevated, suggesting an antagonistic role of these two molecules and their potential role as valuable biomarkers for high-risk patients [54]. sRAGE levels were found to be downregulated in serum, possibly due to enhanced binding to AGE ligands [53].…”