Explaining Complications Associated With Diabetes

New research uncovers a molecular mechanism that links diabetes with an increased risk of cardiovascular problems and sudden cardiac death. The study, published by Cell Press in the June 24 issue of the journal Neuron, finds that high blood sugar prevents vital communication between the brain and the autonomic nervous system, which controls many involuntary activities in the body.

“Diseases, such as diabetes, that disturb the function of the autonomic nervous system cause a wide range of abnormalities that include poor control of blood pressure, cardiac arrhythmias, and digestive problems,” explains senior study author Dr. Ellis Cooper from McGill University in Montreal. “In most people with diabetes, the malfunction of the autonomic nervous system adversely affects their quality of life and shortens life expectancy.”

To investigate why the autonomic nervous system malfunctions in diabetics, Dr. Cooper and colleagues examined the transmission of electrical signals from the brain to autonomic neurons. The brain communicates with autonomic neurons at synapses, a small gap between two nerve cells where electrical signals from one nerve cell are sent to the next by chemical neurotransmitters. “In healthy individuals, synaptic transmission in the autonomic nervous system is strong and stable; however, if synapses on these neurons malfunction due to some disease process, the link between the nervous system and the periphery becomes disrupted,” says Dr. Cooper.

Using a mouse model of diabetes, the researchers discovered that high blood sugar elevates reactive oxygen species in autonomic neurons and causes a disruption in synaptic transmission between the brain and the autonomic neurons. The researchers went on to show that this elevation in reactive oxygen species inactivates the neurotransmitter receptors at these synapses causing synaptic transmission to fail.

“Our work provides a new explanation for diabetic-induced disruptions of the autonomic nervous system,” concludes Dr. Cooper. “We show that an early step leading to autonomic abnormalities in diabetes is a depression in synaptic transmission triggered by events downstream of high blood sugar and reactive oxygen species. This synaptic depression is apparent as early as 1 week after the onset of diabetes and becomes more severe over time.”

The researchers include Veronica Campanucci, McGill University, Montreal, Quebec, Canada; Arjun Krishnaswamy, McGill University, Montreal, Quebec, Canada; and Ellis Cooper, McGill University, Montreal, Quebec, Canada.

Cathleen Genova
Cell Press

How can diabetes damage to the autonomic nerves affect me?

Autonomic nerves help you know your blood glucose is low. Some people take diabetes medicines that can accidentally make their blood glucose too low. Damage to the autonomic nerves can make it hard for them to feel the symptoms of hypoglycemia, also called low blood glucose.

This kind of damage is more likely to happen if you have had diabetes for a long time. It can also happen if your blood glucose has been too low very often.

Drawing of the outline of a body with shaded areas showing the location of the autonomic nerves with the label “Autonomic Nerves.”

Autonomic nerves go from your spinal cord to your lungs, heart, stomach, intestines, bladder, and sex organs.

Autonomic nerves go to the stomach, intestines, and other parts of the digestive system. Damage to these nerves can make food pass through the digestive system too slowly or too quickly. Nerve problems can cause nausea—feeling sick to your stomach—vomiting, constipation, or diarrhea.

Nerve damage to your stomach is called gastroparesis. When nerves to the stomach are damaged, the muscles of the stomach do not work well and food may stay in the stomach too long. Gastroparesis makes it hard to keep blood glucose under control.

Autonomic nerves go to the penis. Damage to these nerves can prevent a man’s penis from getting firm when he wants to have sex. This condition is called erectile dysfunction or impotence. Many men who have had diabetes for several years experience it.

Autonomic nerves go to the vagina. Damage to these nerves can prevent a woman’s vagina from getting wet when she wants to have sex. A woman might also have less feeling around her vagina.

Drawing of a man and a woman facing each other in a bed. Their bodies are covered with a blanket except for their arms, shoulders, and heads. Their heads are resting on pillows. The woman has her arm around the man. They are smiling at each other.

Damage to autonomic nerves from diabetes may cause problems with having sex.

Autonomic nerves go to the heart. Damage to these nerves might make your heart beat faster or at different speeds.

Autonomic nerves go to the bladder. Damage to these nerves can make it hard to know when you should go to the bathroom. The damage can also make it hard to feel when your bladder is empty. Both problems can cause you to hold urine for too long, which can lead to bladder infections. Another problem can be leaking drops of urine accidentally.

Drawing of an older woman standing in front of the toilet. She is slightly bent over and is lifting the lid on the toilet.

Damage to autonomic nerves from diabetes can cause bladder and stomach problems.

Autonomic nerves go to the blood vessels that keep your blood pressure steady. Damage to these nerves can make your blood move too slowly to keep your blood pressure steady when you change position. When you go from lying down to standing up or when you exercise a lot, the sudden changes in blood pressure can make you dizzy.

Drawing of a man seated at a table with his head resting on his right hand. His right elbow is on the table. His eyeglasses are on the table. His eyes are closed and he looks ill.




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