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Stanford University School of Medicine

Insulin resistance is key step toward the “3Ds”: diabetes, depression and dementia

3d-glassesThree of the developed world's major diseases -- diabetes, depression, and dementia -- stem, at least to a significant degree, from a common, treatable, usually preventable and often reversible physiological source: insulin resistance.

Close to one in five Americans are diagnosed with depressive illness at some point in their lives. Meanwhile, about one in three otherwise healthy Americans, and an even greater share of people with depression, are insulin-resistant: Their tissues fail to take up glucose adequately, eventually resulting in high blood levels of the sugar, which is injurious to the body. Most notably, insulin resistance is the direct precursor of type-2 diabetes, increasingly common all over the world; but it also directly increases the risk of heart disease and other problems.

About a decade and a half ago, Stanford brain scientist Natalie Rasgon, MD, PhD, advanced a then-daring hypothesis: Insulin resistance, she proposed, is a missing link between mood disorders and dementia. That hypothesis has since been supported in recent years by an explosion of experimental findings by researchers (including Rasgon) tying not only type-2 diabetes but both depression and Alzheimer's disease to insulin resistance.

Rasgon has just published an opinion piece (subscription required) in Molecular Psychiatry along with noted Rockefeller University neuroendocrinologist Bruce McEwen, PhD, who has delved deeply into the paradoxically opposing roles of stress successful adaptation versus physical and psychological disorders. They write that "among chronic diseases plaguing the modern world, the trifecta of diabetes, depression and dementia is ever growing," making early detection and treatment of insulin resistance ever more imperative.

In middle-aged adults, Rasgon and McEwen write, insulin resistance is associated with disrupted memory and executive function, and corresponding metabolic decline in several key brain areas and the connection between them. While short bursts of manageable stress are actually good for the brain and body, the chronic stress induced by pronounced and protracted episodes of abuse, poverty, obesity-producing diets, weighty workloads, disrupted sleep and disrupted relationships have an opposing effect, mediated in part by the development of insulin resistance. As the co-authors put it:

[T]he neural circuits in a healthy brain are remodeled by experiences to enable behavioral responses that are appropriate to what the individual is experiencing, e.g., begin more vigilant and anxious in a potentially dangerous environment. The healthy brain is resilient and neural circuitry adapts to a new situation... The unhealthy brain is not so plastic; and the brain in someone suffering from [insulin resistance] is less able to adapt and [more] likely to 'get stuck' and need external intervention involving pharmacological agents or behavior (e.g., exercise).

Rasgon and her colleagues have recently shown that insulin resistance can diminish the brain's executive-function prowess even among people less than 45 years old. That makes the early identification and treatment of insulin resistance all the more imperative, she and McEwen argue. I would say it's a pretty irresistible argument.

Previously: Treating insulin resistance may speed recovery from major depression, Estradiol -- but not Premarin -- prevents neurodegeneration in women at heightened dementia risk and Stress hormones moonlight as immune-system traffic cops
Photo by Oona Raisanen

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