The Connection Between Type 2 Diabetes and Alzheimer’s Disease
5 Days Ago By Amy Berger
It’s often said that Alzheimer’s disease is the medical condition people fear most—even more than cancer. This is understandable, considering the staggering statistics around Alzheimer’s and the fact that, at least so far as we currently know, there are no truly effective treatments and no cure. (According to the Alzheimer’s Association in the US, between the years 2000 and 2017, deaths from Alzheimer’s disease (AD) increased 145%,1 while deaths from other noncommunicable conditions, such as heart disease, actually decreased. In the US alone, approximately 5.8 million people are living with Alzheimer’s, and this is projected to more than double to about 13.8 million people by 2050.)
Alzheimer’s may seem mysterious, and the lack of progress toward treatments has been disheartening, but a robust body of scientific evidence suggests that this illness may be a metabolic condition rooted in dysregulated glucose metabolism and insulin signaling.2,3 With this in mind, let’s take a closer look at the connections between type 2 diabetes and Alzheimer’s.
Alzheimer’s disease is sometimes referred to as “type 3 diabetes” and has also been described as “brain insulin resistance.”4,5 In fact, associations between metabolic syndrome (a.k.a. insulin resistance syndrome6) and cognitive impairment are so strong that researchers have coined the term metabolic cognitive syndrome to emphasize these links.7,8,9 The primary malfunction in the brain of someone afflicted with AD is that neurons in affected regions lose the capacity to metabolize glucose properly.10,11 Being unable to harness energy from glucose, these cells atrophy and wither, and the resulting breakdown in neuronal communication may be what leads to the memory loss, cognitive impairment, personality changes, and other hallmarks of the illness.12
What is the connection between Alzheimer’s Disease and type 2 diabetes (T2D)?
We’ve known since the research of Rosalyn Yalow in the 1960s that T2D is a disease of too much insulin (unlike type 1 diabetes in which there is not enough insulin). Many researchers believe T2D is the final stage of chronically elevated insulin. Another factor affecting proper insulin secretion and development of type 2 diabetes is the accumulation of fat in the pancreas. (Compromised liver function resulting from the buildup of fat in the liver is called non-alcoholic fatty liver disease, or NAFLD. The analogous condition in the pancreas is non-alcoholic fatty pancreas disease15, although it is not as widely recognized as NAFLD.) Abnormal accumulation of fat in the pancreas may interfere with healthy beta cell function and insulin secretion, and is associated with increased risk for type 2 diabetes and metabolic syndrome.16,17,18
In some people, chronically elevated insulin can precede a T2D diagnosis by a decade or more. There’s a parallel in Alzheimer’s: in people at risk for AD, reduced brain glucose metabolism is measurable when they’re in their 30s and 40s.19 At this young age, though, they are cognitively healthy and show no signs or symptoms of AD. Even though the brain’s energy supply from glucose is already compromised, the brain is able to compensate and overcome this fuel shortage. It’s only when the damage is so severe and widespread and the brain is no longer able to compensate that problems with cognition and memory begin to manifest.
Turning back to T2D, for many people, the elevated fasting blood glucose or A1c that would trigger a diabetes or pre-diabetes diagnosis is a late development in the disease process. Chronically high insulin preceded this for some length of time, going undetected because measuring insulin levels is not a routine part of a checkup or standard bloodwork. In the same way, it’s possible that the memory problems and cognitive impairment associated with AD are late developments, becoming apparent after years or possibly decades during which the brain has suffered from a progressive decrease in energy.20
Disruptions in either the supply of fuel to the brain or the brain’s ability to use this fuel can have catastrophic consequences for cognitive function. The brain accounts for just 2% of a typical adult’s body weight, but it consumes as much as 20-25% of the body’s glucose and oxygen:
“Given the high energy requirement of the brain and its critical dependence on the delivery of a constant supply of fuel, the consequences of leaving such an energy shortfall untreated can be dire. When the brain’s energy supply is insufficient to meet its metabolic needs, the neurons that work hardest, especially those concerned with memory and cognition, are among the first to exhibit functional incapacity (e.g., impairment of memory and cognitive performance).”21
People with type 2 diabetes have an increased risk for Alzheimer’s disease and other types of dementia compared to those without diabetes.22,23,24 However, even in the absence of high blood sugar, people with chronically high insulin are also at greater risk for AD. In fact, one study showed that risk for AD was highest among people with elevated insulin but who were not diabetic.25 In a study of subjects with newly diagnosed T2D or pre-diabetes who had seemingly normal cognitive function, greater insulin resistance was associated with reduced brain glucose metabolism and subtle cognitive impairments.26 It’s possible that hyperinsulinemia and a disruption in brain fuel usage are the first dominos to fall in the Alzheimer’s cascade, setting the stage for future cognitive decline.
An interesting point to note is that while elevated insulin in the blood appears to be a major risk factor for AD, many AD patients havelower than normal insulin levels in the brain.27,28 Insulin is not required to transport glucose across the blood-brain barrier, nor for neurons to take up and use glucose. However, insulin receptors are scattered richly throughout the brain, and insulin is believed to play a role in facilitating healthy cognition and the viability and proper functioning of neurons.29,30
Chronically elevated blood glucose and/or insulin have negative impacts on nearly every organ and tissue system in the body: the eyes, the kidneys, the skin, the liver, the ovaries, the prostate gland, nerve cells, and more. The brain is no less susceptible to the detrimental effects of deranged glucose metabolism. In fact, owing to its high energy demands, it might even be more susceptible than other parts of the body, and Alzheimer’s disease could be the most severe manifestation of this.
Written by Amy Berger, MS, CNS