Estimation of Apelin and Fibroblast growth factor 21 (FGF21) levels in saliva and serum in generalized periodontitis patients with and without Type 2 Diabetes mellitus (T2DM)

Periodontitis (PD) is a chronic inflammatory disorder mediated by host and bacterial interactions and manifested by damage to the periodontal tissues which may progress to tooth loss. The pathogenesis of periodontitis involves the interaction between periodontal pathogens and host inflammatory and immune responses. Diabetes mellitus (DM) is a cluster of metabolic disorders that are chiefly characterized by hyperglycaemia due to impaired secretion or action of insulin, or both. Several mechanisms have been proposed to explain the biological link between DM and periodontal diseases including the formation of advanced glycation end products (AGEs), changes in collagen metabolism and immune function, and increased oxidative stress.

Apelin (APLN) is a adipocytokine that is encoded by the APLN gene and exerts its functions through autocrine and paracrine pathways by binding to endogenous ligand of the G-protein coupled receptor. It is expressed in various organs & in most cell types including myocytes, smooth muscle cells and fibroblasts. It has been proposed that high apelin levels in people with type 2 diabetes mellitus (T2DM) might be a compensatory mechanism for decreased insulin sensitivity. In reduced levels or absence of insulin, apelin is secreted. This, in turn, decreases the glucose level by increasing the glucose uptake in vital tissues such as skeletal muscle and adipose tissue. Hence, higher levels of apelin are reported in patients with T2DM. Apelin is also released by many cell types in the oral cavity in response to bacterial activity. Periodontitis has been suggested to contribute to adipose tissue inflammation by promoting insulin resistance and insulin-induced apelin expression has been demonstrated in adipocytes.

Fibroblast growth factor 21 (FGF21) is a small molecular weight polypeptide of FGF hormone which is mainly produced in liver and expressed in extrahepatic tissues such as adipose tissue and skeletal muscle. FGF21 plays a crucial role in maintaining tissue homeostasis of both glucose and lipid metabolism and responding to various stressful stimuli, such as inflammation, oxidative stress and hypoxia. The elevation of circulating FGF21 has been closely associated with metabolic disorders including diabetes and is responsible for various actions in energy metabolism and injury protection as a hepatokine, adipokine and myokine in an endocrine or autocrine/paracrine manner, leading to cellular stress resistance and activation of anti-oxidation and inflammation reduction mechanisms.

A state of systemic inflammation induced by periodontitis is a major key linking periodontitis to several diseases such as T2DM. FGF21 and Apelin are protein molecules that potentially involve the inflammatory and immunity response which is a fundamental process in the pathogenesis of diabetes and periodontitis. Therefore, FGF21 and Apelin might be potential biomarkers for linking diabetes to periodontitis.

To the best of our knowledge there are no studies investigating the relationship between Apelin and FGF-21 in periodontal disease and T2DM. Hence, the aim of this study is to comparatively evaluate salivary and serum levels of Apelin and FGF-21 in generalized periodontitis and T2DM.