I’m always wary of new medical terms that seem to be used and promoted prematurely, when still in the hypothesis phase. It seems like an obvious way to bias any thinking about an alleged phenomenon – just label it as the hypothesis, as if it is already a conclusion. Calling symptoms that may follow a lyme infection “chronic lyme disease” implies something that has never been proven.
That was my reaction when I first heard of “Type 3 diabetes”. It didn’t help that it was from a video by such a dubious source as Mark Hyman in which he says, “Scientists now call Alzheimer’s disease Type 3 Diabetes.” Really? I didn’t get the memo.
The underlying idea is a valid research question. Preliminary studies have found that neuronal insulin resistance may be playing a role in the dysfunction and degenerative processes of Alzheimer’s disease. For quick background – insulin is a hormone that allows cells to transport glucose from the blood into the cell to use for energy. Type 1 diabetes results from a decreased ability to create insulin, likely due to an autoimmune disease which destroys the cells of the pancreas that create insulin. Type II diabetes results mainly from insulin resistance, which is partly genetic and partly due to lifestyle factors. Insulin resistance means that it take more insulin for cells to get enough glucose, so people with Type 2 diabetes may actually have increased insulin levels (although the pancreas may then get burned out and not be able to keep up with this increased demand for insulin).
The idea of Type 3 diabetes is that the neurons of the brain have insulin resistance. They are unable to maintain their high demand for glucose, which compromises their function. The brain is a very glucose-hungry organ, so it is plausible that it would be disproportionately affected by insulin resistance.
But biology is complex, and evolution tends to use what’s already there to achieve multiple ends. So it’s not surprising that insulin may have multiple effects in the brain. As a recent review summarizes:
However, emerging evidence from human and animal studies indicate that insulin influences cerebral bioenergetics, enhances synaptic viability and dendritic spine formation, and increases turnover of neurotransmitters, such as dopamine. Insulin also has a role in proteostasis, influencing clearance of the amyloid β peptide and phosphorylation of tau, which are hallmarks of Alzheimer’s disease. Insulin also modulates vascular function through effects on vasoreactivity, lipid metabolism, and inflammation. Through these multiple pathways, insulin dysregulation could contribute to neurodegeneration.
Sounds pretty compelling. Does this mean, as Hyman says, that Alzheimer’s disease (AD) is type 3 diabetes? No so fast. The history of Alzheimer’s research has been one of finding all sorts of clues as to pathological processes associated with AD, that turn out to be just part of the picture. No one process that we have discovered so far has been shown to be the one factor that is causing and driving the disease.
It turns out, when neurons are under some kind of metabolic stress and start to degenerate, there are a lot of downstream effects. Neurons start misbehaving in lots of ways – almost every way we choose to investigate. I have been in neurology long enough to have heard a dozen hypothesis that seemed like we have finally found the one true cause of AD, only to not pan out.
Is it inflammation? Perhaps disrupted axonal transport is the culprit. Genetic variants that correlate with abnormal protein folding seems to be critical. What about oxidative stress, or neurotoxicity? We know a lot about what is happening in AD, and build up of beta amyloid and abnormal tau proteins are certainly playing a key role. But even there, we are now just getting interventions in the form of monoclonal antibodies that seems to modify disease progression (if modestly) by targeting amyloid, with clinical trials of those targeting tau on the way. But again – are we treating the true cause of AD or just one important component of disease progression?
It’s not surprising that glucose metabolism is also abnormal in AD, and that the complex effects of insulin are compromised. Again – most of the cellular functions we look at in AD turn out to be abnormal, at least in a subset of patients.
For now it is reasonable to conclude that it is a good idea to prevent prediabetes or diabetes with good lifestyle habits. It is also good to carefully control blood glucose and insulin resistance in people with these conditions or who are predisposed. This is already the recommendation, so nothing has changed. At most there is one more downstream negative consequence to diabetes that can be improved by good diabetes control.
We can say the exact same thing about hypertension. There is a strong link between high blood pressure and AD risk. There is also a lot of research into the mechanism that connects the two. For now, the best recommendation is to have good blood pressure control – which is already a good idea and standard medical advice. Are scientists now calling Alzheimer’s disease “hypertensive brain”?
AD remains horrifically complex and only partially understood. It is likely a variable set of metabolic processes that have a common final pathway of pathology. There are a lot of risk factors and processes that play a role. At this point it seems like folly to think that there is one true cause of AD.
Insulin resistance seems like it is one of the many things that plays a role in AD pathology. In the short term this reinforces existing advice on preventing and treating diabetes. Perhaps basic research into the mechanisms of insulin’s role in AD may lead to some specific treatments. But it is silly to say that AD should now be known as Type 3 diabetes – unless you are trying to reinforce a simplistic medical narrative by massively overemphasizing the role of diet in every disease.