Reactive oxygen species (ROS) are unstable oxygen molecules, also called free radicals. In type 2 diabetes, high blood sugar that lasts drives ROS up. The excess damages the insulin-making beta cells. It deepens insulin resistance. And it fuels the heart and artery damage that diabetics face.
Type 2 diabetes is the most common metabolic disease currently known to man. Its hallmarks are insulin resistance and pancreatic beta-cell dysfunction (beta cells that no longer work right). Reactive Oxygen Species (ROS) are a little-understood factor in how Type 2 diabetes gets worse. So in this article, I will shed some light on what ROS is. I will also explain the effect it has on this chronic disease.
- What is ROS
ROS is a type of unstable molecule that contains oxygen. It easily reacts with other molecules in a cell. A buildup of reactive oxygen species in cells may damage DNA, RNA, and proteins. It may also cause cell death. Reactive oxygen species are free radicals, also called oxygen radicals.
- How does ROS interact with cellular function?
For a long time, ROS were thought of as useless by-products. They come from respiratory metabolism in mitochondria (the cell’s power plants). They were believed to be generally harmful to living systems. But growing evidence shows that, in many instances, making ROS is not useless or harmful. Instead, it is an essential part of certain biological responses.
ROS, such as H2O2, have been shown to be critical factors in normal cell signaling. They also have the potential to regulate glucose-stimulated insulin secretion (GSIS) in β-cells. Even so, excessive and/or sustained ROS production can do harm. It can directly or indirectly disturb large cell molecules, such as DNA, protein, or lipids (fats). It can harm both their integrity and their physiological function.
- So, when is ROS action harmful?
As discussed above, ROS action is generally helpful. But under diabetic conditions, things change. Chronic hyperglycemia (high blood sugar that lasts) leads to a rise in reactive oxygen species (ROS). Together, they worsen beta-cell function and escalate insulin resistance. This makes type 2 diabetes worse. Chronic hyperglycemia and ROS also play a part in atherosclerosis (hardened, clogged arteries). This artery disease is often seen in people with diabetes.
Such disturbances contribute to the pathogenesis (development) of various diseases, including diabetes. Most cells, including β-cells, have intricate defenses against ROS toxicity. These defenses counter the damage. Among them, the transcription factor NF-E2–related factor 2 (Nrf2) is a pivotal part. It protects cells from oxidative damage.
Under oxidative stress, Nrf2 switches on. It then dramatically raises the cell’s antioxidant power. It does this by directly increasing the transcription of many so-called antioxidant enzymes. So this Nrf2 response is critically important. It keeps proper oxidation/reduction (redox) homeostasis, or balance. That protects cells from oxidative damage that cannot be undone.
But this boosted ability of cells to clear away ROS has a possible downside. It has the potential to blunt normal ROS signals. There has been intensive research on oxidative stress and diabetes. Even so, the role of the cell’s adaptive responses to increased oxidative stress in β-cell dysfunction remains incompletely understood.
- ROS and Cardiovascular Complications in Diabetic Patients
Diabetes mellitus (DM) is an independent risk factor for heart failure. The Framingham Heart Study compared diabetics with control subjects of the same age. It reported that heart failure is 2-fold more frequent in male diabetics and 5-fold more frequent in female diabetics. An increase in reactive oxygen species (ROS) has been regarded as a dominant mechanism of cardiac dysfunction (poor heart function) in patients with DM. ROS are important signaling molecules inside cells. They mediate various cell functions, including activation of transcriptional factors, protein kinases, and ion channels. However, high levels of ROS are harmful to cardiomyocytes (heart muscle cells).
So it can be said that ROS are the main facilitators of cardiovascular complications in diabetes mellitus (DM). Emerging evidence shows the dominant mechanisms of ROS production in the diabetic heart. They are the mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In the diabetic heart, the mitochondria do not work well. Their inner membrane potentials become hyperpolarized (overcharged). Both changes promote ROS production in the mitochondria.
In physiological conditions, the body’s own antioxidant systems keep ROS levels properly controlled. That keeps oxidative damage to cells to a minimum. Oxidative stress occurs when ROS production overwhelms antioxidant capacity in pathological (disease) conditions. ROS production and oxidative stress are clearly increased in the diabetic heart. Oxidative stress brings on various cardiovascular complications, such as cardiac dysfunction. Inflammation, apoptosis (cell death), and fibrosis (scarring) facilitate this.
Multiple mechanisms bring about the rise in ROS in the diabetic heart. Among these, NADPH oxidase and mitochondria play a pivotal role. They stimulate each other to boost ROS production. UCPs regulate ROS production in mitochondria by dissipating the mitochondrial inner membrane potential. PKC, angiotensin II, AGEs/RAGE, and CaMKII facilitate ROS production in NADPH oxidase. The mechanisms of ROS increase in DM are complex. That is because the multiple factors interact and enhance each other.
- What should we expect to see in the future?
Diabetic conditions induce ROS. ROS are possibly involved in the worsening of pancreatic β-cell dysfunction and insulin resistance in type 2 diabetes. Suppression of ROS in obese type 2 diabetic mice restores β-cell function and insulin sensitivity. That leads to amelioration (improvement) of glucose intolerance. ROS is also involved in the progression of atherosclerosis. Under diabetic conditions, atherosclerosis is often seen as a macroangiopathy (disease of the large blood vessels).
Taken together, it is likely that ROS is closely associated with the development of type 2 diabetes and atherosclerosis. So far, several clinical trials with antioxidants show only a little effect, if any, on how type 2 diabetes progresses. Future therapy might look into suppressing ROS. It might also look into infusing stronger and more fitting antioxidants. That could be a way to exert some helpful effects against the development of type 2 diabetes and atherosclerosis.
Related reading
- Beta Cells: What They Do in Diabetes
- Prediabetes and Type 2 Diabetes
- Brain Cholesterol and Alzheimer’s
References
- American Diabetes Association (2007): Reactive Oxygen Species as a Signal in Glucose-Stimulated Insulin Secretion. Retrieved from https://diabetes.diabetesjournals.org/content/56/7/1783
- Hindawi (2009): Role of Reactive Oxygen Species in the Progression of Type 2 Diabetes and Atherosclerosis. Retrieved from https://www.hindawi.com/journals/mi/2010/453892/
- American Heart Association (2018): Reactive Oxygen Species in Metabolic and Inflammatory Signaling. Retrieved from https://www.ahajournals.org/doi/full/10.1161/circresaha.117.311401
- NCBI (2010): Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20182627
- Circulation Journal (2014): Production of Reactive Oxygen Species in the Diabetic Heart. Retrieved from https://www.jstage.jst.go.jp/article/circj/78/2/78_CJ-13-1187/_pdf
Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP
Interventional pain physician, addiction medicine specialist and obesity medicine diplomate.
Licensed in Missouri and Illinois.
Last reviewed June 18, 2026
