According to new research, older persons with newly diagnosed type 2 diabetes mellitus (T2DM) who have a history of stroke or ischemic heart disease may benefit most from treatment with the thiazolidinedione pioglitazone.

In general, over the course of an average of 10 years, patients who took pioglitazone had a 16% lower risk of dementia. This compares to the people who take medication, according to a large cohort study from Korea.

However, the risk of dementia was decreased by 54% and 43%, respectively, among people with ischemic heart disease and stroke histories.

Reports

There will be 139 million cases of dementia worldwide by 2050, with the number continuing to rise. Dementia is more likely to affect some people, particularly those with type 2 diabetes.

Researchers have shown that persons with type 2 diabetes who used the diabetic medication pioglitazone had a lower risk of dementia in old age.

Dementia affects an estimated 55 million individuals worldwide, and by 2050, that figure is anticipated to rise to 139 million.

Type 2 diabetes and dementia

Why would someone with type 2 diabetes have a higher chance of getting dementia?

At Pinehurst, North Carolina, Dr. Karen D. Sullivan, a board-certified neuropsychologist and proprietor of I CARE FOR YOUR BRAIN, claims that diabetes has a detrimental effect on nearly every system of the body, including the brain.

“Compared to people without diabetes, people with type 2 diabetes have a 50–60% increased risk of developing dementia. She stated in an interview with Medical News Today that this is one of the most potent modifiable risk factors for dementia.

She said: “The insulin resistance we detect in diabetes increases atherosclerosis and alters energy metabolism. This results in microvascular alterations in the brain and ultimately a decrease of blood supply to networks of neurons.”

16% lower risk with pioglitazone

Researchers used information on newly diagnosed type 2 diabetics without dementia from the National Korean Health Database for their investigation. The average follow-up period for the more than 91,000 participants was 10 years. 3,467 of the individuals received the medication pioglitazone.

Following examination, researchers discovered that 8.3% of those taking pioglitazone experienced dementia. This is opposed to 10% of those with type 2 diabetes who did not take the medication.

Scientists discovered that persons with type 2 diabetes who took pioglitazone were 16% less likely to acquire dementia later in life after controlling for a number of lifestyle factors. This study was limited by the fact that it was based on data from insurance claims. Therefore it is possible that some participants did not even take pioglitazone.

The study contains no data on the severity of the illness, the participants’ glycemic control, or their genetic susceptibility to dementia.

How blood vessels may play a role

Dr. Eosu Kim is a professor in the Department of Psychiatry in the College of Medicine at Yonsei University in Seoul, Republic of Korea, and the lead author of this study responded when asked how pioglitazone helps reduce the risk of a person with type 2 diabetes developing dementia by pointing out that this study was to investigate the association between pioglitazone use and incidence of dementia, not how — with what mechanisms — this drug can suppress dementia pathology.

Nonetheless, he told Medical News Today, “Several could be recommended based on [the] basic pharmacological activities of this medicine and findings from past studies.”

“First of all, maintaining healthy blood sugar levels is advantageous for brain activities. Also, this medication enhances cells’ capacity for metabolism and encourages them to use bioenergy more effectively. This helps the brain’s insulin resistance.

“Second, certain studies have demonstrated that pioglitazone removes harmful beta-amyloid proteins from the brain. One of the main causes of Alzheimer’s disease is the buildup of beta-amyloid in the brain, he continued.

“Lastly,” he continued, “we hypothesise that pioglitazone’s anti-dementia action may be related to increasing blood vessel health as we found that this medication is more beneficial in diabetic patients who have blood circulation difficulties in the heart or brain than in those without such problems.

Strongest defence in people with heart illness

Speaking about the heart, Dr. Kim and his team discovered that individuals with type 2 diabetes who had previously experienced an ischemic stroke or ischemic heart disease benefited from pioglitazone the most in terms of dementia protection.

Researchers discovered that dementia risk was lowered by 54% in people with ischemic heart disease. Also, by 43% in people with ischemic stroke. Dr. Kim claimed that these outcomes astounded him and his team. It was a surprising discovery, he added.

“Ischemic heart or brain disorders are key risk factors for dementia, thus it would have made sense if pioglitazone’s effects were found to be less effective in those with these conditions. The outcome, though, was the exact reverse of what was anticipated, he said.

Anti-diabetic drugs against dementia

Dr. Kim stated that the next stage of this research is looking at how current anti-diabetic medications or potential medications. These meds enhance cell energy metabolism can inhibit dementia pathogenesis in animal models.

To confirm this medication’s anti-dementia properties and the risk-benefit ratio of using it, prospective trials are required in clinical research. That is, [a] balance between adverse symptoms and advantageous long-term consequences of this medication in terms of dementia prevention,” he said.

Dr. Sullivan replied that the next stage for pioglitazone would be to evaluate long-term safety in people and determine the ideal dose that minimises side effects while maintaining the desired results.

Due to safety concerns, pioglitazone is presently only used as a second-line medication for type 2 diabetes. It is well recognised to raise the risk of fractures, weight gain, and heart failure hospitalisation.

Until then, Dr. Sullivan advised persons with type 2 diabetes to focus on stabilising their blood glucose levels because both high blood sugar (hyperglycemia) and low blood sugar (hypoglycemia) might harm brain blood vessels.

According to her, brain damage occurs when people experience extreme highs and lows.

REFERENCES:

• https://www.medscape.com/viewarticle/988388
• https://www.bmj.com/company/newsroom/older-class-of-type-2-diabetes-drugs-linked-to-22-reduced-dementia-risk/
• https://www.medicalnewstoday.com/articles/type-2-diabetes-drug-may-help-lower-increased-dementia-risk

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