Type 2 diabetes: a new disease mechanism uncovered

Type 2 diabetes: a new disease mechanism uncovered

From left to right: Benjamin Ouimet, Simon Bissonnette, May Faraj and Valérie Lamantia.

Ahead of World Diabetes Day, new work from Dr. May Faraj, Director of the Nutrition, Lipoproteins and Cardiometabolic Diseases Research Unit at the Montreal Clinical Research Institute (IRCM) and Full Professor in the Department of Nutrition at the Université de Montréal, establishes for the first time a new mechanism and role for LDL in the development of type 2 diabetes, beyond its traditional role in the development of cardiovascular disease in humans. 

New evidence stemming from this work suggests in fact that targeting subjects with a high LDL level, by using inflammation reducing interventions may lower the incidence of type 2 diabetes as well as that of cardiovascular diseases, thus achieving two important goals in one single approach.

Every 3 minutes, a new case of diabetes is diagnosed in Canada, mostly type 2, increasing the risk for cardiovascular diseases by 2 – 4 times.

Elevated numbers of particles that carry “bad cholesterol” in the blood, termed LDL, are known to promote the development of cardiovascular diseases.  Clinical evidence originating from Dr. May Faraj’s laboratory 15 years ago, and confirmed in large epidemiological studies, indicate that elevated numbers of LDL also promote the development of type 2 diabetes (T2D) in humans. However, to this day, mechanisms linking LDL to higher T2D risks were poorly understood. 

The Study
To explore these mechanisms, Faraj’s team recruited 40 healthy volunteers between 2013 and 2019 to participate in a study at IRCM that combined clinical and fundamental research. The team separated the 40 subjects into two groups with low and high numbers of LDL. The scientists characterized and compared the two groups for inflammatory responses, carbohydrates and fat metabolism in their adipose tissue and  their whole body. They also isolated subjects’ LDL, fat tissue and immune cells, and examined the direct effects of LDL on the inflammatory responses, in cultures.     

The Findings
Dr. Faraj’s team found that subjects with high numbers of LDL have higher inflammatory responses in their fat tissue than subjects with low numbers of LDL. The regulated inflammatory responses in the adipose tissue of subjects with high LDL only were associated with abnormalities in carbohydrate and fat metabolism in their adipose tissue and body. Over time, these metabolic abnormalities are known to promote the development of T2D if not treated. Finally, in cultures, LDL was able to reproduce the activation of inflammatory responses in subjects’ fat tissue and immune cells, particularly when the LDL was isolated from subjects with high numbers of LDL.  

Full article

Dr. Faraj thanks the research volunteers for donating their time for the benefit of scientific discoveries, and wishes to underlines the hard work and dedication of her team over many years, as well as the precious support and collaboration of the IRCM clinic physicians and nurses, the IRCM technical platforms and the IRCM Foundation. This work would not have been possible without the funding agencies Canadian Institutes for Healthy Research (CIHR) and Canadian Foundation for Innovation (CFI).

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