Repeated Hypoglycemia is Not Directly Linked to Brain Damage

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Hypoglycemia and Brain Damage

Contrary to popular belief, repeated low blood sugar episodes do not appear to cause brain damage.

That’s according to Dr. Alan M. Jacobson, a psychiatrist who is one of the world’s foremost experts on the relationship between diabetes and cognitive function. Jacobson is Director of the Diabetes, Obesity and Cardiometabolic Research Center at Winthrop-University Hospital and served as Director, Psychiatric Services at the Joslin Diabetes Center for more than 30 years.

“We studied this intently and what we found was that hypoglycemia did not appear to confer an additional risk to reduced brain function,” Jacobson says.

Dr. Alan M. JacobsonJacobson was involved in the most comprehensive long-term study of whether hypoglycemia adversely impacts brain function. As part of a team Jacobson studied the effects of improved blood sugar control on type 1 diabetic patients who were participants in The Diabetes Control and Complications Trial—or DCCT. The DCCT tracked 1,441 type 1 diabetic patients ages 13 to 39 for six years to determine whether tighter blood sugar near the normal, non-diabetic range  helped them avoid complications from diabetes, such as retinopathy and kidney disease.     

The landmark study demonstrated definitively that improved blood sugar control leads to a reduction in the incidence of diabetic complications. It also revealed something else.

“Tightening control also leads to an increase in hypoglycemic events,” Jacobson says. “We found a three-fold increase in the number of serious hypoglycemic event in the subjects who had improved blood sugar control.”

This increase in low blood sugar episodes prompted DCCT researchers to gauge whether their number and severity impacted cognitive function. The subjects performed intensive neuropsychological tests over the course of the DCCT and again when patients were being followed in the natural history follow-up- Epidemiology of Diabetes Intervention and Complications (EDIC), and, on average 18 years after they first entered DCCT.

The types of hypoglycemic events that the subjects experienced had a broad range, according to Jacobson. Some subjects had episodes where they merely became lightheaded and woozy from a dip in their blood sugar. Others suffered severe episodes that included seizures, loss of consciousness, and even coma.

“We looked at whether prior severe hypoglycemic episodes affected brain function down the road and we looked at whether a greater number of events conveyed a greater risk of damage overall,” Jacobson says.

The neuropsychological testing was a very thorough four-and-a-half hour battery of tasks that comprehensively mapped the function of the brain, Jacobson says.

Other studies have confirmed Jacobson’s results. In 1999 a study published in the Journal of Cerebral Blood Flow and Metabolism stated, “Fortunately, brain injury from hypoglycemia occurs relatively infrequently in humans.”

The overall results of the DCCT study were published in the New England Journal of Medicine in 1993. The results of the 18 year cognitive follow-up study were published in the New England Journal of Medicine in 2007. The study, however, does not present the definitive opinion on whether hypoglycemia causes brain damage,

“There does remain some controversy associated with the relationship between hypoglycemia and brain damage, despite the study,” Jacobson says.

One reason for the continuing and widely held belief that hypoglycemia must cause brain damage is because the brain runs primarily on glucose. It would seem logical that if the brain were deprived of the fuel on which it runs then damage would occur. Further, when a person suffers a profound hypoglycemic episode they can   suffer brain damage. Jacobson points to the von Bulow case in which Sunny Von Bulow, experienced brain damage that apparently resulted from profound hypoglycemia and led to her living the rest of her life in a vegetative state. Other case reports show similar effects of prolonged and extremely low blood sugars. However as the DCCT/EDIC study shows, the types of hypoglycemia commonly experienced by type 1 diabetes patients do not necessarily lead to brain damage.

There are multiple ways hypoglycemia affects the brain . For example, brain damage can occur through secondary causes, such as loss of cardiovascular function, which then starves the brain of oxygen, causing damage.

Another recent study postulated that the brains of type 1 diabetic patients who suffer repeated episodes of hypoglycemia actually adapt in a positive manner. The results of the study, published in the May 2014 issue of the Journal of Diabetes Investigation, “… suggest that the brain can increase its usage of alternative energy sources when glucose is not sufficient, and this adaptive response can be promoted by repetitive hypoglycemia.”

Jacobson says while the DCCT study is encouraging in reassuring diabetic patients that they don’t have to be afraid of a permanent loss of neurological function as a result of low blood sugar episodes, it is not all-inclusive. For instance, the age range of the study, 13 to 39 years old, does not shed light on how hypoglycemia might impact brain function in older and younger diabetic patients. He also added that the effect of hypoglycemia on the brain in type 2 diabetic patients has not been studied as extensively. Overall, Jacobson says more research into the impact of hypoglycemia on the brain, and the impact of diabetes on the brain in general, is needed.

“This is a reassuring finding,” says Jacobson about the DCCT study and the follow-up 18 years later. “But, it’s not the last word. The effects of diabetes on the brain are subtle and we’re just beginning to understand them.”

Alex O’Meara is a regular contributor to ASweetLife. He writes the blog The Other Side of Diabetes. 

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Comments (3)

  1. Lorraine at

    Interesting. I’d like to know how the same study would affect keto-adapted people since Dr. McCleary in his book The Brain Trust Program, states that the brain (and the heart) prefer ketones as a source of energy.
    I’m not diabetic, but I know that since becoming keto-adapted, I no longer have a hypoglycemic reaction if I go too long without eating like I used to. In fact, I can fast for a very long time with no negative symptoms.

  2. My understanding is that hypoglycemic episodes can lead to brain damage in infants. So that’s not really an issue for people with diabetes unless someone develops diabetes at a very young age, I suppose. Hyperinsulinism, on the other hand, causes frequent, sometimes unrelenting, hypoglycemic episodes at birth.
    As this NIH page ( ) describes, most babies with hypoglycemia (whatever the cause) end up just fine, but there is definitely the potential for brain damage.
    The study in the article seems to suggest that brain damage will not occur if the hypoglycemia is treated reasonably quickly. That is excellent news! I wonder, though, is whether it would occur if treatment were delayed extensively for whatever reason. I’m not sure how that would be tested.

  3. berry palmer at

    Dr O’Meara,
    Realizing that my response here is not timely, I would like to introduce the other side of this dilemma, Post Concussion cognitive memory impairment which, in turn, causes repeated hypoglycemic episodes in borderline Type 1 diabetics.

    I was an over 65yr old, 25yr borderline Type 1 (fully insulin dependent), under good diabetic control when I suffered a severe concussion (5 day comma) from an automobile accident in 2013.

    Post hospitalization, after a severe hypoglycemic episode, I now have a Continuous Glucose Monitor CGM. Even with the CGM, I’ve had several ER visits for hypoglycemic events, followed by ER visits for depression, then panic and anxiety.

    In psychotherapy, my depression, panic and anxiety was diagnosed, likely to be Neurological, rather than clinical. It’s logical that my repeated and sometimes severe hypoglycemia triggers my panic and anxiety as my hormonal thresholds change, but could this all be attributed to Neuroendocrine Dysfunction?

    Forgetfulness is just one of my many conditions that seem to meet the criteria for NED. Even with multiple increasingly more severe hypoglycemic events and worsening post concussion brain functions, my HMO team all but refuses to test and eliminate NED as the cause, while they don’t offer any explanation beyond “clinical” depression, panic and anxiety (for which they’d rather prescribe Prozac or Zoloft).

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