V i v i a n  S o n g
Freelance writer
Freelance writer

Type 3 diabetes

Published in The Toronto Star, January, 2010.

Katherine's father is battling dual enemies in the twilight of his life.

One has been slowly stripping him of his energy and eyesight; the other has been robbing him of his memories.

The two work insidiously in tag-team fashion: With dementia, her father forgets the last time he's eaten; because of Type 2 diabetes, his body is unable to properly convert glucose into energy.

While both can be age-related diseases, a growing body of research is showing an even stronger link that connect the two: Insulin.

So strong is the link, some call Alzheimer's disease, "type 3 diabetes."

Just as insulin produced by the pancreas helps regulate blood sugar levels in the body, scientists discovered that the brain also produces insulin of its own, critical in the formation of new memories.

Couple two growing, national epidemics – obesity and diabetes – with an aging population, and this double threat becomes poised to become a public health concern, experts say.

"Not long ago, it was thought that there was no connection between insulin and the brain, that the brain was insulin-insensitive," said William Klein, a professor of neurobiology and physiology at Northwestern University in Illinois.

"But we now know that's not the case. What's surprising everyone is that it has a specialized function, tied to learning and memory."

The role of insulin in the brain and the link between Type 2 diabetes and Alzheimer's is a multi-faceted one.

Studies have shown that diabetics have a 30 to 65 per cent higher risk of developing Alzheimer's disease.

The diabetic brain is much like the diabetic body, explains Dr. Jack Diamond, scientific director of the Alzheimer Society of Canada.

Either the brain isn't producing enough insulin, which is crucial for memory formation, like Type 1 or juvenile diabetes, or the brain has become insulin-resistant, like Type 2 diabetes.

"In Alzheimer's, brains aren't using glucose properly," Diamond said.

David Schubert, professor of cellular neurobiology at the Salk Institute for Biological Studies in California, didn't mince words when he explained the wider implications of raising a generation of lazy and overindulged children.

"Childhood obesity is a parental responsibility," he said. "People who let their kids get fat should know they're putting their future at risk."

In an online study published last year in Neurobiology of Aging, Schubert conducted an experiment proving that Type 2 diabetes predisposes animals to Alzheimer's. After inducing diabetes in young mice, the animals suffered from significant memory loss and an increase in inflammation of the brain.

His team also found that damage to the blood vessels in the brain occurred well before any overt signs of Alzheimer's disease – like nerve cell death or the accumulation of toxic amyloid deposits in the brain – could be detected.

"Not only did diabetes predispose them to Alzheimer's, it also increases the possibility of getting Alzheimer's at an earlier age."

While the disease normally strikes around 80, diabetics could be at risk of developing Alzheimer's at middle age, he said.

The team to first coin the term "type 3 diabetes" also found that insulin disappears dramatically in Alzheimer's disease.

In the study, produced out of Brown University Medical School, lead researcher Suzanne de la Monte and her team found that as the severity of Alzheimer's increased, the levels of insulin receptors and the brain's ability to respond to insulin decreased.

Likewise, in another study, de la Monte found that obesity and diabetes can also lead to mild neurodegeneration. When she increased the body weight of her animal subjects twofold with a high-fat diet, her team found a significantly reduced mean brain weight to body weight ratio – in other words, the brain shrank.

For Katherine – who asked to remain anonymous to protect the identity of her father, who is still in denial about his dementia – it's not difficult to see how the two diseases are working in tandem.

"I find it hard to decide which is affecting him more," said the Hamilton resident. "With dementia, he forgets that he's hungry or when his last meal was. With diabetes, he's not able to absorb energy from his food."

Similarly, while doctors would have preferred he take insulin pumps to manage his diabetes, dementia prevents it from being an option.

Despite a demonstration on how to use the pump, he couldn't commit the simple instructions to memory, nor would he remember to take the shots regularly. Instead, his children gently remind him to take his pills every day.

While studying how insulin works in the brain, Klein's team at Northwestern also made an important discovery that would show what causes this hormone to fail.

In the brain, insulin and insulin receptors are vital to learning and memory, he said. Insulin is a hormone which binds to receptors at synapses, points of communication between the nerve cells in the brain. It's in this tiny gap where cells communicate with one another – one nerve cell releases a signal, which is received by another. And insulin, Klein discovered, plays a huge role in brain signalling.

While studying amyloid beta-derived diffusible ligands (ADDLs), one of the toxic proteins found in Alzheimer brains that interfere with memory formation, Klein's team found that these toxins worked by attacking and removing insulin receptors from the synapse, rendering the neurons insulin-resistant.

"When insulin signalling is healthy, strong and robust, this phenomenon doesn't happen," Klein said. "Insulin defends the synapse from ADDLs, causing them to disappear. But in the aging process, insulin signalling in the brain can get worse. As a consequence, the brain cells are more vulnerable to ADDLs."

The same team also found that treating Alzheimer's disease with the same drug used to treat Type 2 diabetes could slow or prevent further memory loss caused by these toxic proteins. In a study published year in the Proceedings of the National Academy of Sciences, Klein's research found that insulin and insulin-sensitizing rosiglitazone, protected neurons from ADDLs, a discovery that holds great promise in new drug therapies.

"The exciting aspect is we already have a leg up on the problem."

Sidebar:

CORRELATIONS BETWEEN DIABETES AND ALZHEIMER'S

Some experts call Alzheimer's, "type 3 diabetes" or diabetes of the brain. Here are a few links between the two diseases:

Diabetics increase their chances of developing Alzheimer's by up to 65 per cent compared to those without diabetes.

In Canada, more than 3 million Canadians have diabetes; by 2020, that number is expected to reach 3.7 million.

It's estimated that Alzheimer's disease affects more than 450,000 Canadians; by 2031, that number is projected to more than double.

Research shows that early onset of Type 2 diabetes also increases the chances of developing Alzheimer's earlier.

Like the pancreas, the brain produces insulin. Researchers believe Alzheimer's develops when the brain becomes insulin-resistant, much like Type 2 diabetes.

In the brain, insulin and insulin receptors are crucial to learning and memory. Insulin binds to receptors at synapses in the brain – points of communication – helping nerve cells to survive and memories to form.

Diabetes can lead to faster cognitive decline in Alzheimer's patients.

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