Simple Summary

Metabolic syndrome, and type 2 diabetes (T2D) are related disorders that damage (among other things) the brain.  Both conditions contribute to impaired cognitive function, and increase the risk of Alzheimer’s.

More Detail

Metabolic syndrome is characterized by belly fat, elevated cholesterol, elevated blood pressure, insulin resistance, increased risk of blood clots and inflammation.  Metabolic syndrome, if uncorrected, eventually damages the pancreas leading to a decrease of insulin secretion.  “The fall in insulin secretion leading to hyperglicemia occurs as a late phenomenon and, in fact, separates the patients with metabolic syndrome from those with or without overt diabetes.”(R)

Persons with metabolic disorders are at significantly increased risk for cognitive decline and the development of vascular dementia and Alzheimer’s disease.  Those with T2D are at even greater risk.

Into The Weeds

Insulin Resistance:

Insulin is a peptide hormone produced by the Beta cells in the pancreas which also serve as glucose level monitors. As the beta cells in the pancreas detect increasing levels of glucose (a simple sugar) they step up insulin production.

When someone is insulin resistance, their cells are unable to take up glucose, and the result is hyperglycemia (an increase in circulating glucose). Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level.

Insulin resistance has at least two contributing factors.  Cortisol, a stress induced hormone, counteracts insulin.  This contributes to hyperglycemia and inhibits the utilization of glucose, which eventually leads to insulin resistance.  Inflammation has a host of sources and has also been implicated in causing insulin resistance.  Both cortisol and inflammation have links to Alzheimer’s (R).

Insulin and insulin receptor levels in the brain decrease with normal aging.  Alzheimer’s is associated with a decrease in insulin receptor expression in the brain.  Insulin resistance and impaired insulin signaling are associated with increases in Alzheimer’s pathology.  So it may be that insulin resistance contributes to Alzheimer’s and Alzheimer’s contributes to insulin resistance, which in turn accelerates Alzheimer’s progression.  At this point we are in a chicken-versus-egg scenario within a negative feedback loop, but the bottom line is that insulin resistance and Alzheimer’s are strongly correlated.  Here’s the full study from two University of Southern California researchers, published in April 2014 that looks into some of this: Alzheimer’s Disease and Type 2 Diabetes: Multiple Mechanisms Contribute to Interactions.


Obesity causes an increase in inflammatory cytokines not only in body fat but also in the nervous system.  Obesity also causes inflammation in many brain regions.  In Alzheimer’s, inflammatory pathways have been widely hypothesized to directly contribute to disease initiation and progression (R).

Inflammation is part of the immune response throughout the body.  In the brain the monitoring and cleanup of abnormalities is handled by two cell types, astrocytes and microglia.  High levels of pro-inflammatory cytokines are often observed in the brains of those with Alzheimer’s and those cytokines keep the astrocytes and microglia activated and busy.

ApoE and Testosterone:

Here then are three separate factors that correlate with an increased risk of developing Alzheimer’s.  They are T2D, ApoE 4, and low testosterone (I won’t go into a full discussion of ApoE or Testosterone here).  The significance of these factors is that your risk of developing Alzheimer’s increases even more when the factors exist in combination.  In other words, diabetes is bad, but if you have low testosterone or the genetic risk factor known as ApoE 4, you are at even greater risk of developing Alzheimer’s.

Final Thoughts

There are many inputs to the pathobiology of diabetes and Alzheimer’s.  This article has looked at several important inputs and the connections between the two diseases.  Next we will look at a diabetes treatment that shows promise for Alzheimer’s.