Diabetes: What impact does blood sugar have on depression risk?

• An estimated 5% of all adults around the world live with depression.
• Fluctuations in a person’s blood sugar levels are a known risk factor for depression.
• Researchers from Sun Yat-sen University believe reduced gray matter volume in the brain may mediate the link between blood sugar levels and depression risk.

About 5% of the entire world’s adult population lives with depression — a mental disorder leaving a person feeling very sad and hopeless to the point where they do not enjoy their normal activities.

There are quite a few risk factors for depression, one of which is fluctuations in glycemia or a person’s blood sugar levels.

Previous studies show that people with diabetes — a condition where a person has trouble keeping their blood sugar at a healthy level — have a two to three times higher risk of having depression.

Now, researchers from Sun Yat-sen University in Guangzhou, China believe they have found a specific biological mechanism responsible for the correlation between blood sugar levels and depression.

Researchers reported that a reduced gray matter volume in the brain may mediate the link between blood sugar levels and depression risk.

This study was recently published in the journal Global Transitions.

Blood sugar, brain structure, and depression 

Dr. Hualiang Lin, professor in the Department of Epidemiology at Sun Yat-sen University and corresponding author of this study, told Medical News Today they decided to study the impact of blood sugar on depression risk because previous studies have confirmed the correlation between fluctuations in blood sugar levels and the onset of depression.

“Additionally, extensive research has indicated a strong association between changes in brain structure and function and the development of depression. Therefore, the existing evidence strongly suggests that brain structure may play a mediating role in the comorbidity of diabetes and depression. Consequently, we conducted this study to further investigate this relationship,” Dr. Lin continued.

Previous research has shown a link between changes in gray matter volume in the brain and depression. A study in 2019 found specific alterations in gray-matter volume were associated with lifetime major depressive disorder.

And a study in 2022 found that reduced hippocampal gray matter volume was a common feature in people with major depression, bipolar disorder, and schizophrenia spectrum disorders.

Observing gray matter in the brain

During this observational study, Dr. Lin and his team used data from more than 500,000 participants of the UK Biobank ages 40–69.

Upon analysis, scientists found a “significant correlation” between elevated levels of glycosylated hemoglobin, HbA1c, reduced gray matter volume, and depression.

HbA1c is a simple test that measures a person’s blood sugar levels — or glycosylated hemoglobin — from the past three months.

Researchers reported a lower gray matter volume was associated with depression, and this association was seen the most in study participants with prediabetes, compared to those with or without diabetes.

“Although this result aligns with our hypothesis, we are still very excited about it,” Dr. Lin said.

“Previous research on detailed brain structures associated with depression has been relatively limited, often focusing on well-known clinical regions like the hippocampus or prefrontal cortex. In contrast, our study utilized MRI data from hundreds of brain structures, enabling us to better extensively explore and uncover potential gray matter structures that may be related to depression,” he said.

Age as a factor in heightened risk

Additionally, the association between lower gray matter volume and depression was highest in study participants aged 60 years or older.

“This finding has significant implications in public health, particularly for the neurological well-being of older individuals,” Dr. Lin explained.

“Specifically, the results show that for every one unit increase in HbA1c, the reduction in gray matter volume is more pronounced in individuals over the age of 60 compared to younger individuals. In some brain regions, the difference can be more than double.”
— Dr. Hualiang Lin

“Given the global trend of population aging and the increasing risk of diabetes, this finding suggests that we may face heightened risks to brain health and mental well-being in the future,” he added.

What is a healthy blood sugar level? 

Blood sugar — also known as glucose — plays an important role in many of the body’s functions. For starters, it is the body’s primary source of energy. And glucose is what “feeds” the brain, keeping it and its accompanying nerve cells working and communicating with each other.

The body obtains blood sugar from the food you eat, especially carbohydrate foods starchy vegetables, whole grains, and fruits. As the body breaks these foods down in the digestive system, glucose is released into the bloodstream.

As the amount of glucose in the bloodstream rises, the pancreas begins to release insulin. Insulin helps the glucose get into the body’s cells to provide the energy it needs.

High fasting blood sugar levels may indicate a person has or is at risk for developing diabetes:

• A fasting blood sugar level of 99 mg/dL or lower is considered healthy
• A fasting blood sugar level between 100 to 125 mg/dL signals prediabetes
• A fasting blood sugar level of 126 mg/dL or higher indicates a person has diabetes

Symptoms of too much glucose in the body’s bloodstream — known as hyperglycemia — include:

• intense thirst and/or hunger
• frequent urination
• headaches
• tiredness
• mood changes
• blurred vision

Could blood sugar control reduce depression?

After reviewing this study, Dr. Daniel Pompa, cellular health expert, author of the “Cellular Healing Diet,” and host of a weekly Cellular Healing TV podcast and YouTube show told Medical News Today it has long been known that blood sugar levels play a significant role in brain health, so this study reinforces that understanding.

“High glycemic levels lead to inflammation of the brain, resulting in decreased cognitive abilities and emotional regulation. Long-term exposure to high glucose levels has been linked to an increased risk of developing depression due to changes in neural pathways.”
— Dr. Daniel Pompa

“Higher levels of glycosylated hemoglobin (HbA1c) lead to decreased brain volume in individuals with prediabetes and type 2 diabetes. This has been confirmed by a number of previous studies, which have found that elevated HbA1c is associated with lower gray matter volumes in areas like the hippocampus, thalamus, and prefrontal cortex,” Dr. Pompa continued.

Dr. Pompa said he would like to see further research on the effects of lifestyle changes and fasting as a way to improve type 2 diabetes, along with brain scans to determine gray matter volume in these individuals.

“Specifically, can reducing type 2 diabetes symptoms halt or even reverse the destruction of gray matter as well as reduce rates of depression?” he added.

“Unfortunately, depression is quite common in people living with diabetes, and there’s not much known as to the connection,” commented Dr. Matthew J. Freeby, assistant clinical professor of medicine, director of the Gonda Diabetes Center, and the associate director of Diabetes Clinical Programs at the David Geffen UCLA School of Medicine. “Research into the topic is much needed for understanding both cause and potential treatment.”

Dr. Freeby told MNT that although this research is an interesting observation, he does not think we can yet pinpoint physical changes in gray matter volume as a cause.

“We need head-to-head prospective trials and ones that assess function,” he added.

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