An insulin pen with disposable needles.
Tuesday, February 21, 2023

New research finds serious hypoglycaemic events in type-2 diabetes patients are linked to dementia

Waterloo School of Pharmacy researchers have found that in patients with type-2 diabetes experiencing severe hypoglycaemic events, where blood glucose levels fall below normal to potentially dangerous levels leading to either a hospitalization or physician visit, is consistently linked with the development of dementia.

Previous research studies have shown that type-2 diabetes is a risk factor for Alzheimer’s disease and other types of dementia. Using more than 20 years’ worth of healthcare data from British Columbia, Waterloo Pharmacy researchers and colleagues conducted two complementary epidemiological studies.

First, they found that among patients with type-2 diabetes, those who experience at least one severe hypoglycaemic episode have an 80% risk of all-cause dementia compared to those not experiencing a severe hypoglycaemic episode. Second, they found this increased risk of dementia was consistent among persons experiencing their first serious hypoglycaemic event in their mid-life or their late life.

Wajd Alkabbani at a poster presentation event.

Wajd Alkabbani

“We assumed if you have a hypoglycaemic event at a young age that the brain bounces back. Our research has found that whether experienced in mid or late life, a severe hypoglycaemic event can double the risk of developing dementia,” Wajd Alkabbani says, PhD student at the School.

Some people may experience low blood sugar while using insulin due to many reasons such as skipping a meal or increasing their amount of activity. In both situations a severe hypoglycaemic event could occur when exogenous insulin is given. Incorrect dosing of insulin can also lead to such episodes.

"Several previous studies have shown there is a relationship between serious hypoglycaemic episodes and the risk of a new diagnosis of dementia. Our findings complement and extend this prior knowledge using epidemiological methods to combat various threats to validity and by testing the association among dynamic cohorts with different eligibility based on age” says Dr. JM Gamble, Alkabbani’s PhD supervisor at the School.  

Findings from both studies by Alkabbani and colleagues support current clinical practice which aims to prevent hypoglycaemic events through evidence-based prescribing and dose optimization of antihyperglycemic agents with a high risk of hypoglycaemia. Patients with diabetes need to work closely with their caregivers to consistently administer doses correctly and with their physicians to adjust doses where there’s a concern that a hypoglycaemic event may occur.

“Dementia is complicated – as some manifestation of dementia occur before the official diagnosis. We also don’t know when dementia starts exactly because a lot of pathophysiological symptoms occur long before a patient is diagnosed. Therefore, implementing proper research techniques at the study design or analysis stage is critical when conducting dementia research using real-world health data” Alkabbani says.

Short term implications of these studies are to focus on preventing hypoglycaemic events irrespective of patients’ age. Long-term implications are to further research mechanisms by which hypoglycaemic events is associated with dementia.

Two studies, Associations of Mid- and Late-Life Severe Hypoglycaemic Episodes With Incident Dementia Among Patients With Type 2 Diabetes: A Population-Based Cohort Study and Hypoglycaemia and the risk of dementia: a population-based cohort study using exposure density sampling, were co-authored by Wajd Alkabbani, PhD in progress and J.M. Gamble, PhD.

This work also included dementia and diabetes experts Colleen Maxwell, PhD and Suzanne Tyas, PhD from the University of Waterloo, Iliana Lega, MD from the University of Toronto, and Ruth Ann Marrie, MD, PhD from the University of Manitoba. Alkabbani’s PhD is funded by the Mike and Valeria Rosebloom Foundation Research Award at the Alzheimer’s Society of Canada.