Diabetes (Type II)

What is Type 2 diabetes?

Type 2 diabetes, also known as non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes, is a chronic metabolic disorder characterized by insulin resistance, impaired insulin secretion, and high blood sugar levels. Unlike type 1 diabetes, which results from autoimmune destruction of insulin-producing beta cells in the pancreas, type 2 diabetes typically develops gradually over time and is associated with a combination of genetic, lifestyle, and environmental factors.

In type 2 diabetes, the body’s cells become resistant to the effects of insulin, a hormone produced by the pancreas that helps regulate blood sugar levels. As a result, glucose is unable to enter cells efficiently, leading to a buildup of sugar in the bloodstream, known as hyperglycemia. To compensate for insulin resistance, the pancreas increases insulin production, but over time, the beta cells may become exhausted and unable to produce enough insulin to overcome insulin resistance, resulting in further elevation of blood sugar levels.

What is the relationship between Type 2 diabetes and oxidative stress?

The relationship between type 2 diabetes and oxidative stress is significant, as oxidative stress plays a pivotal role in the development and progression of the disease and its associated complications. Here’s how oxidative stress influences type 2 diabetes:

• Insulin Resistance: Oxidative stress contributes to the development of insulin resistance, a key feature of type 2 diabetes. Reactive oxygen species (ROS) generated during oxidative stress can impair insulin signaling pathways in target tissues such as skeletal muscle, liver, and adipose tissue, leading to reduced glucose uptake and utilization. Oxidative stress-induced insulin resistance results in elevated blood sugar levels and compensatory hyperinsulinemia, which can further exacerbate oxidative stress and contribute to the progression of type 2 diabetes.

• Beta Cell Dysfunction: Oxidative stress can impair the function and survival of pancreatic beta cells, which are responsible for producing and secreting insulin. Chronic exposure to high levels of glucose, free fatty acids, and inflammatory cytokines in individuals with insulin resistance and type 2 diabetes can increase ROS production in beta cells, leading to oxidative damage, mitochondrial dysfunction, and apoptosis (cell death). Beta cell dysfunction and apoptosis contribute to the progressive decline in insulin secretion and worsening hyperglycemia in type 2 diabetes.

• Lipotoxicity and Inflammation: Dyslipidemia, characterized by elevated levels of circulating free fatty acids and triglycerides, is common in individuals with type 2 diabetes and contributes to the pathogenesis of the disease. Excess free fatty acids can accumulate in tissues such as skeletal muscle, liver, and pancreatic islets, where they can undergo lipotoxicity, a process characterized by oxidative stress, mitochondrial dysfunction, and inflammation. Lipotoxicity-induced oxidative stress and inflammation contribute to insulin resistance, beta cell dysfunction, and impaired glucose metabolism in type 2 diabetes.

• Endothelial Dysfunction: Oxidative stress plays a key role in the development of endothelial dysfunction, a hallmark feature of cardiovascular complications associated with type 2 diabetes. Reactive oxygen species (ROS) generated during oxidative stress can damage vascular endothelial cells, disrupt endothelial function, and promote atherosclerosis, hypertension, and thrombosis. Endothelial dysfunction impairs vasodilation, increases vascular permeability, and promotes inflammation and thrombosis, contributing to the increased risk of cardiovascular disease in individuals with type 2 diabetes.

• Complications of Diabetes: Oxidative stress is implicated in the development and progression of complications associated with type 2 diabetes, including cardiovascular disease, nephropathy (kidney disease), retinopathy (eye disease), neuropathy (nerve damage), and peripheral vascular disease. Chronic hyperglycemia, dyslipidemia, and inflammation in diabetes promote the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), leading to oxidative damage to blood vessels, tissues, and organs throughout the body. Oxidative stress-induced damage to vascular endothelial cells, extracellular matrix proteins, and cellular signaling pathways contributes to the pathogenesis of diabetic complications by promoting inflammation, fibrosis, and oxidative damage in affected tissues.

Overall, oxidative stress plays a central role in the pathogenesis of type 2 diabetes by contributing to insulin resistance, beta cell dysfunction, inflammation, endothelial dysfunction, and the development of diabetic complications.