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Exploring A Biological Link Between Diabetes and Alzheimer’s Disease: What You Need to Know

Explore groundbreaking research that connects type 2 diabetes and Alzheimer's disease through mitochondrial dysfunction. The link unveils new insights in elder care and disease prevention.

Elderly people with diabetes often require more support from loved ones to manage their condition and take care of their health. This can be even more complicated for individuals that also have a neurodegenerative condition like Alzheimer’s disease

Nearly 30% of people aged 65 and older live with diabetes, and studies show that type 2 diabetes is a primary risk factor for neurodegenerative conditions. This connection has led scientists to investigate possible biological links for further clues. 

Mitochondria – energy powerhouses under fire

Diabetes disrupts the body's natural mechanisms for maintaining sufficient energy in the cells. One consequence of this imbalance appears in a key regulator of cell energy – mitochondria. These power generators create energy for our cells to go about their daily business. 

“They are like energy-producing factories in ourselves,” said Afshan Malik, Ph.D., a diabetes researcher at King's College London. “When we breathe oxygen, it travels to our blood, inside cells, and ends up in the mitochondria, where it's used to convert glucose to energy.”

Some organs are busier than others and need more energy to function, like the heart, kidney, and brain. “In an individual kidney cell or neuron (brain messenger cell), there are 100s-1000s of copies of mitochondrial DNA,” she said. 

Malik explained that organs with many mitochondria are more vulnerable to damage. Her research investigates the genetic consequences of diabetes on kidney, eye, and liver function. In every organ, Malik comes across the same pattern. 

“When you have [high blood sugar], you can change mitochondrial function in cells and organs in the body,” she said. 

These changes result in an energy shortage and trigger a damaging process called oxidative stress

“If you're tired and lacking energy, you stop doing all the usual things…taking care of yourself, cleaning your house, getting rid of the trash,” Malik said. “It's similar for the cell. If an energy crisis starts, then the cell stops doing some of its basic housekeeping tasks.”

As part of her research, Malik wondered if this pattern would appear in another high-energy organ: the brain

“I was curious to see if a similar underlying molecular change was happening in Alzheimer's disease as in people with diabetes,” she said. “And yes – I see similar changes.”

Diabetes of the brain

Malik’s insight builds on growing evidence that points to mitochondria as a link between Alzheimer’s and type 2 diabetes. Studies have found that people with type 2 have roughly a 50% higher risk of developing Alzheimer’s disease later in life.

Dr. Russell Swerdlow, a professor at the University of Kansas School of Medicine, has studied mitochondria in Alzheimer’s patients for decades. He also directs KU’s Alzheimer’s Disease Research Center, Neurodegenerative Disorders Program, and the Heartland Center for Mitochondrial Medicine. 

According to Swerdlow’s research, genetics determine how efficient mitochondria are and how these cell powerhouses age. 

“Think of this as the distance from the [Alzheimer’s disease] cliff at the time of birth and the rate at which one approaches the [Alzheimer’s disease] cliff as they age,” said Swerdlow. “As our mitochondria become less efficient as we age, we can initially compensate. But eventually, the amount of compensation needed exceeds our ability to meet that need.”

Alzheimer’s disease pathology overwhelms aging mitochondria, leaving them more tired and less able to function properly. These changes are not unlike those observed in other organs and tissues in people with type 2 diabetes

“My best guess is that the state of the mitochondria in the brain and other tissues, such as the muscle, reflect each other,” said Swerdlow. 

Malik and Swerdlow agreed that energy imbalances in the brain and body are intrinsically linked. Both Alzheimer’s disease and type 2 diabetes “share a common underlying driver, which in this case is stressed mitochondria, Swerdlow said. In the brain, the clinical manifestation is Alzheimer’s disease, and outside the brain, the clinical manifestation is type 2 diabetes – “hence the association,” he said. 

How to care for your mitochondria

Impaired mitochondria in diabetes and Alzheimer’s are an emerging topic that requires more research. However, mitochondrial markers in patient blood samples may act as an early warning sign of disease. 

A recent study found that samples from Alzheimer’s disease and patients with type 2 diabetes have lower levels of two mitochondrial protein markers compared to control subjects. Lower protein levels were also a reliable predictor of cognitive decline from mild cognitive impairment to Alzheimer’s disease. 

Therapeutic targeting of the relationship between type 2 diabetes and Alzheimer’s disease has shown promise with a common diabetes drug, metformin. Previous clinical studies report a possible protective effect of metformin for type 2 diabetes patients against developing Alzheimer’s disease. 

Still, it remains unclear how metformin may impact cognition as studies have conflicting results. Currently, healthcare professionals recommend metformin only as a first-line preventative measure for type 2 diabetes patients. 

While many other therapies in this realm have failed in clinical trials, researchers remain undeterred. 

“The era of using rational mitochondria-targeted therapies to treat neurodegenerative diseases and metabolic conditions is only just beginning. I think there is promise, but there’s still a long way to go,” said Swerdlow. 

For now, the best preventive measures to protect your health are those known to be tried and true: diet and exercise as well as taking medications if needed for high cholesterol (especially LDL), high blood pressure, and high blood glucose. 

“Take care of your mitochondria,” said Swerdlow. “Get adequate exercise and eat a healthy diet to [minimize] the impact of related chronic conditions, such as hypertension.” 

Swerdlow’s comments align with research supporting diet and exercise as a potentially beneficial Alzheimer’s prevention strategy. The Centers for Disease Control also advises managing blood sugar and maintaining a healthy weight to reduce the risk of neurodegenerative conditions.

“Good glycemic control is really important,” said Malik. “When glucose spikes too high or too low, [it can] cause a lot of oxidative stress to the body. If this persists over a long time, that's when the damage happens.”

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