Propolis Improves Periodontal Status and Glycemic Control in Subjects With Type 2 Diabetes Mellitus and Chronic Periodontitis: a Randomized Clinical Trial

INTRODUCTION

Diabetes mellitus (DM) is a metabolic disorder characterized by frequent periods of hyperglycemia, which induce certain molecular pathways that seem to be crucial to the initiation of angiopathic complications of DM. Several mechanisms have been suggested to explain the pathogenicity of complications of hyperglycemia such as protein kinase C isoforms, enhanced polyol pathway flux, and increased accumulation of advanced glycosylated end-products. A dysregulated immune response stemming from an inappropriate cytokine production is a possible mechanism underpinning the cross-susceptibility between periodontal disease and DM. DM has been unambiguously determined as one of the major risk factors of periodontitis. It was reported that the risk of periodontitis increases to almost threefold in diabetic patients when compared to healthy individuals. The glycemic control level is believed to be of paramount importance as a determinant of the increased risk for developing complications. Diabetic patients with an HbA1c level more than 9% were found to have an increased prevalence of advanced chronic periodontitis in comparison to healthy people according to the US National Health and Nutrition Examination Survey (NHANES) III.

Two decades ago, periodontitis was added to represent the sixth complication of DM. Individuals suffering from periodontal diseases often have increased serum levels of proinflammatory cytokines, such as IL-1, IL-6 and TNF-α. Diabetic patients with periodontitis possess hyperinflammatory immune cells that lead to enhanced release of proinflammatory cytokines, which eventually lead to insulin resistance resulting in a greater risk of poor glycemic control when compared to diabetic patients without periodontitis. The accumulation of irreversible advanced glycation end-products (AGEs), predominantly N€-(carboxymethyl) lysine (CML) has shown to alter cell function and tissue structure. Due to difficulty in managing diabetes; there is a critical need for new therapeutic modalities for prevention of diabetes-related complications.

Propolis is a natural resin synthesized by honey bees from substances extracted from parts of some plants, buds and sap. Due to its physical characteristics, propolis is utilized by the honey bees to protect the hives against foreign invaders. Propolis has been used for centuries as a homeopathic medicine known for its anti-inflammatory properties, especially in Europe and ancient Egypt. It has traditionally been used for the management of numerous diseases, such as gastrointestinal disorders and mucocutaneous infections of fungal, bacterial and viral etiology.

There are several types of propolis that differ in composition depending on the plant source which varies according to the geographic zone such as Brazil, Peru, China and Europe. Propolis contains more than more than 230 constituents, including flavonoids, cinnamic acids and their esters, caffeic acid and caffeic acid phenethyl ester. It has been found to have a wide array of biological activities, including antibacterial, antiviral, fungicidal, anti-inflammatory, antioxidant, hepatoprotective, free radical scavenging, immunomodulatory and anti-diabetic activity. Recently, investigations revealed that caffeic acid phenethyl ester (CAPE) is an important active molecule found in propolis and is responsible for most of its therapeutic properties.