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Amygdalar Activity Associated with Increased Risk for Diabetes

Key findings

  • Higher baseline metabolic activity in the amygdala (a neural tissue critically involved in stress) predicted subsequent development of type 2 diabetes mellitus in humans, in a retrospective study
  • The association between higher amygdalar activity and diabetes risk remained robust after accounting for T2DM risk factors
  • Increased amygdalar activity was synergistic with adiposity in promoting diabetes
  • The results suggest a "two-hit" mechanism (high adiposity plus increased neurobiological response to stress) that may inform novel therapeutic strategies

Psychological stress seems to contribute to the development of diabetes mellitus, according to epidemiologic studies. In addition, stress negatively affects glycemic control in people who already have diabetes. However, the mechanism of this link between stress and diabetes is still unknown.

Metabolic activity can now be measured in areas of the brain known to be activated by psychological stress. Studies utilizing this advancement have detected increased signaling in the amygdala in people who have chronic stress conditions such as anxiety or post-traumatic stress disorder.

At Massachusetts General Hospital, researchers are measuring amygdala activity (AmygA) with a powerful integrated imaging technique called 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT). An added benefit is that 18F-FDG-PET/CT can simultaneously measure visceral adipose tissue (VAT), a potent risk factor for diabetes.

Michael T. Osborne, MD, Ahmed Tawakol, MD, co-director of the Cardiac MR PET CT Program, and colleagues have become the first to show that AmygA predicts future development of type 2 mellitus diabetes (T2DM). In Psychoneuroendocrinology, they report the observation that this mechanism is independent of adiposity, as well as synergistic with adiposity, in increasing T2DM risk.

As part of a study of AmygA and cardiovascular events, the researchers reviewed 232 individuals who underwent 18F-FDG-PET/CT at Mass General between 2005 and 2008. The subjects did not have T2DM at baseline and had at least one year of medical records available.

Amygdalar Activity Independently Predicted T2DM

AmygA as a continuous variable was significantly associated with T2DM risk in univariate analysis of the patients, the researchers found. The association persisted in a multivariate analysis adjusted for baseline blood glucose, history of pre-diabetes, age, sex, and other well-established predictors of T2DM.

The link between AmygA and T2DM was particularly strong when the researchers categorized AmygA as low (less than the median value) versus high (the median value or higher). Individuals with high AmygA had about a five-fold increased risk of T2DM. Notably, high AmygA independently predicted T2DM even in individuals who were overweight or obese, as defined by either baseline body mass index (BMI) or baseline VAT.

Synergy Between Amygdalar Activity and Adiposity

Next, the team explored how the relationship between AmygA and adiposity might affect T2DM risk. They categorized individuals as having high or low AmygA and as having high or low adiposity.

The analysis was conducted three times, each time using a different measure of adiposity: BMI ( Across all analyses, low AmygA was associated with a low risk of T2DM, regardless of adiposity. Conversely, individuals with both high AmygA and high adiposity were at greatest risk.

A "Two-Hit" Mechanism

Thus, high adiposity and the neurobiological response to stress appear to combine to increase the risk of T2DM, the researchers conclude. This "two-hit" mechanism suggests novel targets for the treatment of T2DM and possibly for prevention as well.

For now, the authors say, the results emphasize the need to consider psychosocial stress when assessing which individuals are at high risk of T2DM.

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A team of clinicians led by Ahmed A. Tawakol, MD, co-director, Cardiac MR PET CT Program, has found a novel pathway linking psychosocial stress to heart disease. Published in the The Lancet, this study finds that brain activity in the stress-responsive area of the brain (the amygdala) predicts subsequent heart attacks and stroke.


Ahmed Tawakol, MD, co-director of the Cardiac MR PET CT Program, discusses the link between stress and atherosclerotic disease, and his team’s work using multimodality imaging to better understand that risk.