19th June 2022

Higher risk of stroke can follow midlife type 2 diabetes

By Medical News

Medical News - New research on thousands of twins in Sweden has uncovered a significant link between type 2 diabetes in midlife and the risk of stroke and blocked brain arteries later in life. However, the link did not apply to brain bleeds, which can also cause strokes.

Strokes are serious attacks in the brain that deprive nerve cells of oxygen by cutting off their blood supply. Without oxygen, cells soon begin to die.

Researchers from establishments in Sweden and China carried out the new study. They wanted to examine the relationship between midlife type 2 diabetes and cerebrovascular disease later in life and find out whether genetics and family background played a role.

They defined family background as including factors such as "shared childhood socioeconomic status and adolescent environment." By studying twins, they hoped to gain insights on these potential influencers.

However, when they analyzed the results, they concluded that the link between type 2 diabetes in midlife and the risk of stroke later was independent of genetics and upbringing.

In a Diabetologia paper, the authors remark that the findings "highlight the need to control midlife type 2 diabetes to help prevent blockage or narrowing of cerebral arteries in late life and reduce the incidence of strokes caused by such blockages."

Cerebrovascular disease is a group of conditions that affects the brain's blood supply. There are two main types of cerebrovascular disease, depending on what happens to blood vessels: ischemic and hemorrhagic.

Ischemic cerebrovascular disease is one that reduces the flow of blood. This can happen when a blood vessel narrows or suffers a blockage.

Hemorrhagic cerebrovascular disease is the loss of blood when a blood vessel ruptures.

While both types of disease can lead to stroke, the vast majority of strokes are of the ischemic type.

According to the World Health Organization (WHO), stroke and diabetes are two of the top 10 causes of death worldwide.

Global estimates for 2016 suggest that stroke killed nearly 6 million people, and diabetes killed close to 1.6 million that year. The vast majority of people with diabetes have type 2.

The study authors explain that both type 2 diabetes and cerebrovascular disease "are complex genetic and lifestyle-related disorders." Scientists have implicated genes and upbringing in the development of both.

However, what is not clear is whether genetics and family environment also contribute to a potential link between type 2 diabetes and cerebrovascular disease.

Twins typically share the same genes and have the same environment before birth and through childhood and adolescence. This makes them ideal subjects for the study of diseases in which scientists want to explore the role of genes and family background.

The latest research took in individuals from the Swedish Twin Registry. This nationwide registry, which is based at the Karolinska Institutet, is the largest of its kind and started in the 1960s.

The Karolinska Institutet regularly administers batches of questionnaires to individuals in the registry. One of these batches was a Screening Across the Lifespan Twin study (SALT) that collected data between 1998 and 2002 from twins over 40 years of age.

The recent study used SALT data from twins who were still alive at the end of 2014 and who had not reached their 60th birthday before this date.

The researchers also excluded anyone who: had type 1 diabetes; developed type 2 diabetes before the age of 40 or after the age of 60; developed cerebrovascular disease before the age of 60; or who experienced a mini-stroke, or transient ischemic attack.

This filter left 33,086 individuals — 14,969 males and 18,117 females — with SALT data for the analysis. In addition to the usual demographic information, such as age, sex, and education level, the dataset included information on medication use, smoking status, alcohol use, weight, height, and genetic similarity.

By consulting Sweden's National Patient Registry, the researchers were also able to find out which individuals in the cohort developed diabetes and cerebrovascular disease.

Putting all the information together, the investigators found that 1,248 (3.8% of the cohort) had diabetes during the ages of 40–59 years and 3,121 (9.4% of the cohort) developed cerebrovascular disease at 60 years of age or later.

When they analyzed the results, the team found that — compared with not having diabetes — having type 2 diabetes in midlife was tied to double the risk of developing narrow arteries after 60 years of age.

The analysis also showed that there was a tie between type 2 diabetes in midlife and a 30% higher risk of experiencing a severe blockage in a brain artery, which often results in a stroke.

The analysis found no link, however, between type 2 diabetes in midlife and hemorrhagic cerebrovascular disease — either intracerebral hemorrhage or subarachnoid hemorrhage — in later life.

When they ran the analysis, the researchers removed the effects of potential influencers, such as age, sex, education level, marital status, body mass index, cigarette and alcohol use, having heart disease, and having high blood pressure.

They used a "co-twin match analysis" to compare data from "discordant twin pairs," meaning pairs in which one twin had the condition, and the other did not.

The team suggests that biological explanations for a link between type 2 diabetes and cerebrovascular disease are likely to be complex and unclear.

People with type 2 diabetes tend to have abnormal levels of fats in their blood. They can also experience a much faster rate of atherogenesis, a condition in which arteries grow fatty deposits.

Metabolic disruption arising from various factors could be another reason why type 2 diabetes might make cerebrovascular disease more likely. These factors might include increased blood sugar and fatty deposits, inflammation, insulin resistance and its knock-on effect of raised insulinproduction.

To explain the lack of a link between type 2 diabetes and hemorrhagic cerebrovascular disease, the researchers suggest that this could be due to the way that type 2 diabetes alters the lining of blood vessels.

People with type 2 diabetes tend to have more cells in the lining of their blood vessels. This tendency could reduce the likelihood of a rupture and raise the chance of a blockage.

The team points to two main drawbacks of their study. The first is that there were insufficient numbers of twin pairs in which only one twin developed cerebrovascular disease. The second drawback was that they could not be certain of taking full account of genetic factors because they did not distinguish between identical and nonidentical twins.

Finally, because the SALT questionnaires did not ask for data on eating habits and exercise, the team could not consider these factors in their analysis.

The authors suggest that, given these drawbacks, "large, longitudinal twin studies are warranted for further clarification."