Type 2 diabetes: a new disease mechanism uncovered

Newswise — Published just before World Diabetes Day, work by Dr. ^May Faraj, director of the Research Unit on Nutrition, Lipoproteins and Cardiometabolic Diseases at the Montreal Clinical Research Institute (IRCM) and full professor at the Department of Nutrition at the University of Montreal, highlight a new mechanism and a new role for LDL – commonly called bad cholesterol – in the development of type 2 diabetes, LDL already being involved in cardiovascular diseases in the human.

The results of this work show that targeting people with high LDL levels using interventions that reduce inflammation can reduce the incidence of type 2 diabetes as well as cardiovascular disease, leading to achieve two important goals in one approach.

Every three minutes, a new case of diabetes is diagnosed in Canada, mainly type 2, a condition that increases the risk of cardiovascular disease by two to four times.

We know that a high number of particles carrying “bad cholesterol” in the blood promotes the onset of cardiovascular diseases. Clinical data from Dr. Faraj's laboratory ¹⁵ years ago and confirmed by large epidemiological studies indicate that high LDL also increases the risk of suffering from type 2 diabetes in humans. However, until now, the mechanisms linking LDL to the risk of type 2 diabetes were still poorly understood.

Participants with low or high bad cholesterol

To explore these mechanisms, May Faraj's team recruited 40 healthy volunteers between 2013 and 2019 for a study at the IRCM combining clinical and fundamental research. The team separated the subjects into two groups, based on whether they had low or high LDL levels. The scientists characterized and compared inflammatory responses, carbohydrate metabolism and fat metabolism in adipose tissue and in the whole body in participants from both groups. The team also isolated LDL, adipose tissue and immune cells from the subjects and examined the direct effects of LDL on inflammatory responses in culture.

Abnormalities of carbohydrate and lipid metabolism

The research team found that subjects with high LDL levels had greater inflammatory responses in their adipose tissue than subjects with low LDL levels. Regulated inflammatory responses in the adipose tissue of subjects with elevated LDL only were associated with abnormalities in carbohydrate and lipid metabolism in their adipose tissue and in their bodies. Over time, these metabolic abnormalities are known to promote the development of type 2 diabetes if left untreated. Finally, in culture, the team was able to reproduce the action of LDL on inflammatory responses in the subjects' adipose tissue and immune cells, particularly when LDL was isolated from subjects with high LDL counts.