The connection between stroke and metabolic health
High blood sugar and metabolic dysfunction is associated with increased stroke risk. Here's what the latest research says about the connection.
Decades of research have shown that people with Type 2 diabetes face between 1.5 and two times the risk of stroke compared to people without diabetes. Even more compelling is that approximately one-third of all people who have strokes have diabetes.
Although this link between diabetes and stroke is strong, it may be an oversimplification to say that diabetes itself raises stroke risk.
Instead, it’s likely that the underlying conditions of Type 2 diabetes (and a similar condition known as metabolic syndrome—a set of markers that includes high blood pressure, elevated blood glucose, high triglycerides, low HDL (“good”) cholesterol, excess abdominal fat, and high blood pressure) may contribute to stroke risk in their own ways. But clearly, developing evidence suggests that elevated risk of stroke in people with diabetes is related to hyperglycemia, otherwise known as high blood glucose.
Below, we’ll take you through what is currently known about the connection between diabetes, metabolic syndrome, fasting glucose, and stroke and explain what we’re still learning, along with some things you can do now to lower your risk.
The Link between Diabetes, Blood Glucose, and Stroke
Large-scale epidemiological studies, which study disease incidence in large populations, have established a strong connection between diabetes and stroke. One meta-analysis of 102 studies published in The Lancet in 2014 concluded that people with diabetes (about 7% of nearly 700,000 people studied) had double the risk of stroke compared to people without Type 2 diabetes.
Scientists are unraveling it by working backward to understand why that connection exists. They’re investigating whether the various factors involved in diabetes underlie increased stroke risk.
The Connection between Metabolic Syndrome and Stroke
Metabolic syndrome is a cluster of conditions including high blood pressure, high triglycerides, high fasting glucose (over 100 mg/dL in this study), and a waist circumference over 40 inches in men and 35 in women. It can be a step toward Type 2 diabetes, defined as having fasting glucose above 125 mg/dL. Research on metabolic syndrome, which shares many factors with diabetes, is helping to determine the circumstances that lead to stroke risks becoming significant.
One study published in The Journal of Stroke in 2016 compared differences in stroke risk in people who were “metabolically healthy,” people with metabolic syndrome, and those with diabetes. It included approximately 5,000 people, 162 of whom had strokes over the nine-year study period. The study found that people with diabetes had a 50% higher risk of stroke compared to people who were metabolically healthy. Notably, people who didn’t have diabetes but had metabolic syndrome had a 30% higher risk compared to metabolically healthy people.
That might seem like a high risk, but only 162 people out of 5,000 people had strokes in this population in the first place. In other words, while the risk of stroke is significantly higher for people with diabetes and metabolic syndrome, the baseline risk was low to begin with. Still, the work suggests that some aspect of metabolic syndrome makes strokes more likely than not having metabolic syndrome and that diabetes increases the risk even more. The likely overlapping factor: high glucose.
The Relationship between High Fasting Glucose and Stroke
A study published in the journal Stroke in 2005 set the stage for that idea, looking at the risk of ischemic stroke (loss of blood flow to the brain due to a blood clot or narrowed artery) and transient ischemic attack (a stroke-like event sometimes called a mini-stroke) in more than 14,000 people in Israel with a history of heart disease. Of that group, 614 people experienced strokes. It found that people with metabolic syndrome had a 49% higher stroke risk than those without metabolic syndrome. The two markers that raised stroke risk: high blood pressure and high fasting glucose (above 110 mg/dL—note that this is still well below the threshold for diagnosing Type 2 diabetes, which is 126 mg/dL).
The findings clarified that high fasting glucose could have a more significant role in raising stroke risk. The authors of that study built upon that idea in another paper, where they tried to pinpoint the level at which increased fasting glucose became a contributor to stroke risk.
That study followed nearly 14,000 people who had participated in a clinical trial for heart disease treatment in Israel. The 576 people in that population who eventually had strokes and mini-strokes were split into groups based on their fasting blood glucose levels. The relationship between stroke risk and glucose levels followed a “J-shaped” curve: People with low and high blood glucose saw an elevated stroke risk, but the latter had a far higher risk. People with blood glucose below 80 mg/dL had a 22% greater risk of stroke compared to people with regular blood glucose (between 90–99 mg/dL), while people with blood glucose between 110–125 mg/dL had a 60% higher risk than the “regular” group. Glucose levels between 126–140 mg/dL bumped the increased risk to 82% over those with regular blood glucose.
In short, stroke risk was the lowest for people who were neither hypoglycemic nor hyperglycemic, and those whose blood glucose trended toward prediabetic or diabetic blood glucose levels faced higher risk.
More recent research supports this, even in minor or additional strokes: A 2019 study on people who had previously had minor strokes, for example, found that people with consistently high blood glucose (between 110–126 mg/dL) had a 1.5-fold increased risk of having another stroke in the three months following their stroke compared to people with normal blood glucose (people with diabetes had a 2.5-fold increase). The risk of stroke was also slightly higher in people with fasting glucose levels higher than 100 mg/dL.
It’s important to note that the connection between high fasting glucose and stroke risk is still being debated. A meta-review of 15 studies on prediabetes and stroke risk published in the BMJ in 2012 threw cold water on the connection after finding that in eight of the studies, the relationship between prediabetes and stroke could be attributed to chance after adjusting for cardiovascular risk factors such as obesity, physical inactivity, and hypertension. In that same paper, however, five of the studies showed a strong connection between prediabetes and stroke risk even after adjusting for cardiovascular risks. In short, persistently high blood sugar was still linked to stroke risks, even though the strength of the connection varies. (A factor that complicated this review is that the blood sugar parameters for prediabetes were defined differently among the studies.)
The review concluded that people with high fasting blood glucose (between 110–125 mg/dL) had a 20% higher stroke risk than people with normal blood glucose levels. While it might seem like a big step up in risk, the baseline risk of having a stroke was low across all the studies involved. According to the authors, “the absolute risk would be modest.”
In sum, there is clearly a connection between fasting glucose levels, diabetes and metabolic syndrome, and stroke risk. However, scientists are still looking for the critical point at which high blood glucose becomes an issue.
Why is there a Connection between Diabetes, Blood Glucose, and Stroke?
Even if it doesn’t rise to the level of diabetes, poor metabolic health—particularly fasting glucose-—has ties to a higher risk of stroke. One reason appears to be that strokes are diseases of the blood vessels, and diabetes may increase stroke risk because it also affects blood vessels.
Strokes occur because a blood vessel either bursts (called a hemorrhagic stroke) or becomes blocked (ischaemic stroke). A hemorrhagic stroke allows blood to pool in brain tissue, damaging brain cells. In contrast, an ischaemic stroke cuts off blood supply to the brain, starving it of oxygen. Diabetes is more common among people with ischemic strokes as opposed to those experiencing a hemorrhagic event, but it’s a risk factor for both types. High glucose levels in the blood contribute to the buildup of clots or deposits in blood vessels. This narrows them, eventually restricting blood flow and thus the amount of oxygen that reaches the brain. Plaques that develop in the carotid artery, which supplies blood to the brain and neck, can lead to increased stroke risk.
Another way high blood glucose affects the blood vessels is by causing oxidative stress, which activates a series of cellular pathways that can ultimately lead to the stiffening of arterial walls. The stiffening of arteries that feed blood to the brain can contribute to stroke risk. This is also one reason diabetes is linked with heart disease. The increased risk of stroke intensifies when high blood pressure, a hallmark of both diabetes and metabolic syndrome, enters the mix. Over time, high blood pressure can damage blood vessels or increase the pressure inside them, leading to a rupture.
What is oxidative stress and why does it matter to metabolic health?
Metabolic Basics
There also appears to be a link between uric acid and stroke risk. Elevated blood sugar increases uric acid. Uric acid inhibits nitric oxide, which leads to less vascular relaxation, increasing the risk of stroke and hypertension.
The relationship between specific fasting glucose levels and stroke still isn’t fully understood, in part because much of the research has focused on people with fasting glucose so high they already qualify as having diabetes. The point at which fasting glucose becomes linked to higher stroke risk could occur at a lower fasting glucose level. For now, it’s unclear when that point will happen.
Further complicating the research is that when people have strokes, their fasting glucose tends to spike immediately, which makes studying the link between fasting glucose and stroke risk difficult. Strokes are traumatic events that trigger the body’s fight or flight response, and the subsequent release of stress hormones can spur the release of glucose stored in the liver or trigger other glucose manufacturing processes. Meanwhile, inflammatory cytokines released as part of the fight or flight response can also increase insulin resistance, keeping the supply of blood glucose high. This process is called “stress hyperglycemia.”
> “Healthy eating and exercise are vital parts of the fundamental stroke-prevention toolkit.”
Some stroke survivors end up with persistently high blood glucose levels that reach into prediabetic ranges, even if they don’t have a history of diabetes. As one 2014 review paper on prediabetes and stroke notes, the prevalence of prediabetes in people who had a minor stroke or TIA is 37% within the first three months of the event and 32% after three months.
Scientists have debated whether the stroke causes this spike in blood glucose or if underlying, undiagnosed glycemic issues are also at play. The relationship, for now, is unclear. As the authors of a 2019 review paper on diabetes and stroke outcomes points out, many studies on acute stroke and fasting glucose use blood glucose measurements taken when people are admitted to a hospital, which is when they might already be experiencing stress glycemia.
That caveat doesn’t discount the fact that glucose dysregulation, and especially diabetes, contribute to stroke risk in the first place. But it does suggest that this relationship could be more complicated than it appears.
What can you do about the connection between metabolic health and stroke?
When it comes to lowering the risk of having a stroke in the first place, there are no magic bullets. Maintaining healthy eating habits, getting regular exercise, and avoiding smoking are some essential boxes to check. If you’re recovering from a stroke, keeping an eye on blood glucose can be critical.
Eat Healthy and Exercise
Healthy eating and exercise are vital parts of the fundamental stroke-prevention toolkit. Plant-based diets are a good place to start. One study published in 2021 pulled data from three long-term surveys encompassing roughly 209,000 people. Those who regularly ate “healthful” plant-based diets—based mainly around leafy greens, beans, and whole grains but included some meat—had a 10% lower risk of stroke.
A study published in 2020, which evaluated how certain foods affected stroke risk among 418,000 people over 12 years, showed that eating fruits and vegetables, along with yogurt, milk, and cheese, was linked with lower ischaemic stroke risks. Meanwhile, red meat was linked to higher stroke risks.
110 Foods unlikely to spike your blood sugar
Nutrition
Studies have also found exercise is linked to lower stroke risk. A 2013 study that followed 1,700 people in Japan with Type 2 diabetes over eight years found that those who engaged in regular light exercise (equivalent to roughly 30 minutes of brisk walking every day) had half the stroke risk of those who exercised less.
There are still unanswered questions. For example, a 2018 review paper summarizing the relationship between exercise and stroke prevention notes that “a substantial body” of work has proven that exercise can reduce the burden of risk factors (like high blood pressure or cholesterol) associated with strokes. But it also points out that we still lack high-quality research on the impact of increased physical activity on mortality and morbidity—in other words, does more exercise reduce actual death from stroke.
Quit Smoking
Smoking is consistently linked with both heart disease and stroke. One meta-analysis, for example, reviewed 14 studies on smoking and risk covering more than 303,000 people. It found that more smoking is linked with a higher risk of stroke: for every five cigarettes smoked per day, the risk of stroke increased by 12%.
Quitting can reduce that risk significantly. In that meta-analysis, current smokers had a 46% higher risk of stroke than non-smokers (people who had never smoked). Former smokers also had lower stroke risks: The study found that the likelihood of stroke was 92% higher for current smokers, whereas it was 30% higher for former smokers.
Aim for Stable Glucose (especially if you’ve had a stroke already)
Stress-induced hyperglycemia can increase the risk of having another stroke. In a study published in Aging in 2021, a team of scientists in China followed roughly 3,000 patients for 90 days after they had minor strokes or stroke-like events. Most of the patients (70%) didn’t have diabetes, 20% had diabetes, 7% had newly diagnosed diabetes-related hyperglycemia, and 2% had hyperglycemia related to their strokes. The last group didn’t have diabetes; their hyperglycemia came from their strokes.
People in the latter stroke-related hyperglycemia group had nearly ten times the risk of having another stroke than those without diabetes. They had over five times the risk of having another stroke compared to people who had previously been diagnosed with diabetes. In short, glucose levels post-stroke may be an even more significant risk factor for another stroke than diabetes itself.
Scientists are still ironing out why high glucose post-stroke may usher in another one. One working idea is that spikes in blood glucose trigger the release of pro-inflammatory cytokines, increasing inflammation within the body. Other research suggests that glycemic “swings”—bouncing from hyperglycemia to hypoglycemia and back again—are related to oxidative stress, which can damage the inner lining of blood vessels.
This research suggests that it’s worth keeping an eye on blood glucose levels after a stroke. A doctor may even prescribe insulin treatments in the aftermath of a stroke to get blood glucose under control.
The importance of blood glucose in the context of stroke depends on your medical history. If you’ve already had a stroke, watching blood glucose levels is a critical part of treatment. If you have diabetes, know that the risk of stroke is certainly elevated. If you have hyperglycemia or prediabetes, there is less direct evidence of an increased stroke risk; however, improving your metabolic health so that you don’t progress to diabetes will keep your overall risk lower.
