Is high blood sugar tipping you closer to dementia? Why a new multi-national study may have answers

Dr R.M. Anjana, president, Madras Diabetes Research Foundation, says collaboration efforts like these are intended to combine multi-disciplinary expertise and diverse datasets to identify early indicators of brain aging in people with diabetes, paving the way for new preventive and therapeutic advances.

How diabetes increases the risk of dementia or Alzheimer’s disease

Diabetes, especially if not well-controlled, increases the risk of vascular disease, which is basically narrowing, blockage or weakness of arteries and veins, leading to reduced blood flow to organs. “It likely increases the risk of cerebrovascular disease, especially small vessel disease (a condition where the walls of the body’s small arteries become damaged, reducing blood flow to vital organs like the heart, brain, kidneys, and retina),” says Prof Henrik Zetterberg, head, Department of Psychiatry and Neurochemistry, University of Gothenburg, and visiting faculty at CBR. In an email response, he explains how these obstructions may reduce the brain’s capacity to withstand brain changes related to Alzheimer’s like clusters of certain proteins (amyloid beta plaques and tau tangles). These cannot be cleared out then.

“There may also be a primary link between hyperinsulinemia (high levels of insulin) and defective amyloid beta clearance. High insulin can inhibit amyloid degradation by enzymes. This could lead to amyloid beta build-up in the brain and an increased risk of protein misfolding (when protein chains don’t fold properly and become toxic) and amyloid beta plaque formation. Exactly what is the most important process is not known and something we believe our project will give an answer to,” he writes.

Why controlling blood sugar can help protect the brain

The brain needs the right amount of glucose. “Too much makes one tired and too little can make one irritable and anxious. Very low levels (for instance if insulin is accidentally overdosed) can make one unconscious and even kill neurons. Hence controlling blood sugar helps protect blood vessels in the brain so that they can keep their ability to deliver oxygen to the brain cells. Similarly it may also prevent hyperinsulinemia. It may thereby promote clearance of amyloid beta clusters by keeping insulin levels normal,” Prof Zetterberg adds.

Why research is needed to prevent long-term impact

Prof K V S Hari, Director, Centre for Brain Research, IISc, Bengaluru, explains that while diabetes is believed to have negative effects on cognition, there is inadequate evidence from large-scale population studies. “There are research studies that indicate how diabetes could increase the risk of dementia by causing insulin resistance (a condition in which the body’s cells do not respond optimally to the hormone insulin) and chronic inflammation leading to neuronal damage. This affects how the brain uses glucose (which it needs for energy), leading to possible disturbances in brain function,” he says.

Diabetes may also alter neurotransmitter function that further impacts mood and behaviour, according to Prof Hari. “Hence diabetes and cognitive decline have a dual relationship, where each condition can impact the other. Diabetes can increase the risk of cognitive decline, and conversely, cognitive decline can make it harder to manage diabetes due to impaired decision-making or adherence to treatment,” he says.

Diabetes is now recognised as an important risk factor, contributing about 2% to the global dementia risk, as highlighted by the Lancet Commission report of 2024. In India, the prevalence of diabetes is particularly concerning, with approximately 101 million people affected by the condition, and an additional 136 million people living with prediabetes, according to the ICMR-INDIAB study. “This high burden underscores the urgency of better prediction and management strategies to counter long-term cognitive effects,” Prof Hari says.