Oxidative Stress and Diabetic Complications: The Role of Antioxidant Vitamins and Flavonoids

Abstract

Diabetes mellitus is a group of disorders of multiple aetiologies resulting from a defect in insulin secretion, insulin action, or both. Insulin deficiency in turn leads to chronic hypergly‐ cemia (very high blood glucose levels) with disturbances in carbohydrate, fat and protein metabolism [1]. The two major types of diabetes mellitus (DM) are insulin dependent (IDDM) - type 1 and non -insulin dependent (NIDDM) -type 2. Type 1 DM is characterized by a specific destruction of the pancreatic β cells commonly associated with immune-mediated damage [2]. Individuals with type 2 DM display a gradual change in glucose homeostasis due to insulin resistance and/or decreased insulin secretion [3]. Sustained hyperglycemia leads to the progressive development of long-term microvascular and macrovascular complications which causes morbidity and mortality among those affected [4, 5]. Although glycemic control has long been the mainstay for preventing the progression of diabetic complications, there is far less evidence that these interventions reverse diabetic complications [6]. Also, limitations in intensive glycemic treatment such as difficulty in achieving and/or maintaining tight glycemic control [7], incidence of hypoglycemia and increased mortality [8, 9] suggest an urgent need for alternative and/or complementary therapies to this disorder. Hyperglycemia-induced oxidative stress is now recognized as the driving force for the development of diabetic complications [10]. Oxidative stress in diabetes results in stimulation of the polyol pathway, formation of advanced glycation end products (AGE), activation of protein kinase C (PKC) and subsequent formation of reactive oxygen radicals [11, 12]. Hyperglycemia, not only generates more reactive oxygen species (ROS), but also attenuates antioxidative mechanisms by scavenging enzymes and substances [13].