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Diabetes Types and Insulin Resistance in Alzheimer's Disease

Updated on October 30, 2017
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Linda Crampton is a teacher with a first class honors degree in biology. She writes about human biology and the scientific basis of disease.

Structure of the pancreas
Structure of the pancreas | Source

Types of Diabetes

Many people have heard of type 1, type 2, and gestational diabetes. Another type exists, however—the type 3c version of the disease. Doctors say that it’s being misdiagnosed, which could have unfortunate consequences for patients. It might be wondered why the condition isn’t simply known as type 3 diabetes. That term is also used, although controversially at the moment. Some researchers say that Alzheimer’s disease should be reclassified as type 3 diabetes.

All of the currently accepted kinds of diabetes involve a problem with insulin, a vital hormone that controls the blood sugar level. Researchers are discovering that an insulin problem also seems to be involved in Alzheimer's disease. The evidence for this link is growing stronger, although there is some uncertainty about the details. Understanding the connection might be very important in preventing the disease and perhaps even in treating it.

Location of the pancreas in the abdominal cavity
Location of the pancreas in the abdominal cavity | Source

Functions of the Pancreas

Insulin is made by the pancreas, which is located on the left side of the body behind the stomach. The pancreas is an interesting organ because it contains two distinctly different types of tissue. Both of these are relevant in a discussion of diabetes. The pancreatic islets (or islets of Langerhans) produce the hormones insulin and glucagon, which regulate the blood sugar level. The body system that produces hormones is known as the endocrine system, so the islets are sometimes referred to as endocrine tissue. Hormones are released into the bloodstream.

A pancreatic islet is surrounded by cluster of cells. Each cluster is called an acinus. The plural form of the term is "acini". The acini produce digestive enzymes that are sent through a duct into the first part of the small intestine, or the duodenum. These enzymes include trypsinogen, lipase, and pancreatic amylase. Trypsinogen is converted to trypsin in the duodenum and then digests protein. Lipase digests fats and pancreatic amylase digests starch. The pancreatic system that produces enzymes is referred to as an exocrine system because it releases its products into a duct.

The pancreatic islet is in the middle of this stained slide. The acini surround the islet.
The pancreatic islet is in the middle of this stained slide. The acini surround the islet. | Source

Function of Insulin

Inusulin is made by the beta cells in the pancreatic islets and released into the bloodstream. It then binds to specific receptors on the membranes of cells. This triggers the entrance of glucose (blood sugar) into the cells, which use the chemical as a source of energy. As a result, blood sugar is lowered.

Another hormone called glucagon triggers the release of stored glucose from the liver into the bloodstream if the blood sugar level falls too low. Glucagon is made by the alpha cells in the pancreatic islets.

In a person without diabetes, the combined action of insulin and glucagon maintains a fairly constant blood sugar level. This is important because low blood sugar can be dangerous for the functioning of the brain. Both low and high blood sugar are harmful for the body as a whole if the conditions exist for too long, however. Controlling the amount of sugar in the blood is a vital activity in the body.

People with type 1 diabetes need to measure their blood sugar level frequently.
People with type 1 diabetes need to measure their blood sugar level frequently. | Source

People with type 1 diabetes need supplemental insulin. People with type 2 and 3c diabetes may or may not require insulin as part of their treatment.

Type 1, Type 2, and Gestational Diabetes

Type 1 diabetes is an autoimmune condition. For an unknown reason, the patient's immune system attacks and destroys the beta cells in the pancreas. The patient must receive insulin injections in order to replace the action of the pancreas.

In type 2 diabetes, cells in the body become resistant to the presence of insulin. Glucose is unable to leave the blood and enter the cells. In addition, the pancreas may be unable to make enough insulin for the body's needs. Blood sugar stays high unless the person is given a treatment to overcome or compensate for the problems. The cause of type 2 diabetes isn't known for certain. It's often (but not always) linked to genetics, lifestyle problems leading to obesity, or a combination of these factors.

Gestational diabetes is a temporary condition that sometimes develops during pregnancy. It's thought to be produced when hormones from the placenta interfere with the action of insulin in the mother.

Understanding Type 2 Diabetes

Insulin resistance is a growing problem in most developed countries; the American Diabetes Association says more than half of adults older than 64 have pre-diabetes, in addition to the 29 million with full-blown diabetes.

— University of Wisconsin-Madison School of Medicine and Public Health

Type 3c or Pancreatogenic Diabetes

Type 3c diabetes involves damage to both the endocrine and the exocrine tissue in the pancreas. The tissue in the pancreas is damaged by inflammation, cancer, or surgery. As a result, the patient lacks both insulin and digestive enzymes. He or she needs to be treated for both the insulin deficiency and the enzyme one.

Unfortunately, according to a recent survey by some British researchers, most cases of type 3c diabetes are misdiagnosed as type 2. This means that patients aren't getting all of the treatments that they need. They may need both insulin and enzyme supplements. In fact, according to the researchers, people with type 3c diabetes are more likely to need supplemental insulin than people with the type 2 version of the disease.

One factor affecting the incorrect diagnosis may be that the condition sometimes develops years after the injury to the pancreas, making it less likely that a connection to the injury will be made.

Difference Between Alzheimer's Disease and Dementia

Researchers have made two significant discoveries. Alzheimer's disease is often accompanied by insulin resistance. In addition, experiencing insulin resistance seems to increase the risk for Alzheimer's disease. The evidence for each discovery is getting stronger.

Alzheimer's Disease

Alzheimer's disease is a progressive neurodegenerative condition involving memory loss and an inability to reason, learn, and make decisions. The patient also develops problems with communication and in performing everyday activities. Sadly, the disease leads to death at the moment.

Our genes "tell" the body to make certain proteins. A protein is a long chain of amino acids that is folded into a specific shape. If this shape changes for some reason, the protein can't do its job.

In Alzheimer's, misfolded forms of a protein called beta-amyloid collect in clumps called plaque between brain neurons, or nerve cells. The plaques are sticky and are believed to play a major role in the disease. In addition, misfolded tangles of another protein called tau collect inside the neurons. Some researchers think that these play an even more important role in the disease than the beta-amyloid.

Although misfolded proteins in and around nerve cells certainly seem to play a role in Alzheimer's disease, insulin resistance may be important in the development of the disorder as well.

A Link Between Insulin Resistance and Memory Loss

Insulin Resistance and Memory Problems

Joint research by scientists from Iowa State University and the University of Wisconsin-Madison has revealed some interesting information. 150 people in late middle age with no obvious cognitive or memory problems received blood tests to detect their fasting insulin level. They also receive a PET scan to detect which parts of their brain were actively using sugar. In addition, they were given memory tests.

Some of the participants had a link to Alzheimer's disease or diabetes in one or more ways.

  • 103 of the participants had a parent with Alzheimer's disease.
  • 40% of these 103 participants also had a gene associated with the disease.
  • Seven of the participants had type 2 diabetes.

The researchers found that the higher the degree of insulin resistance in the partipants, the lower the sugar utilization in their brain. (Scientists have found that insulin resistance can develop in brain cells as well as in other parts of the body.) The parts of the brain that were affected included the left medial temporal lobe, which is known to play an important role in memory. Perhaps significantly, it's also the area where Alzheimer's disease appears to start. Researchers also found that the participants with low use of sugar in their brain performed worse on memory tests.

What is especially interesting—and worrying—about the research is that if the people hadn't taken part in the experiment, they would not have known that they had memory problems or (except in the case of the people with type 2 diabetes) insulin resistance. Even at the early stage of resistance to the hormone, memory was being affected.

Protein Problems in Alzheimer's Disease

While not all research confirms the connection, many studies suggest people with diabetes, especially type 2 diabetes, are at higher risk of eventually developing Alzheimer's dementia or other dementias.

— Mayo Clinic

Metformin and Alzheimer's Disease

The research described above is one part of the evidence showing that insulin resistance can lead to memory problems. Experiencing problems with memory doesn't necessarily mean that a person has or will develop Alzheimer's disease, though. There is evidence suggesting that insulin resistance increases the risk for the disease, however. One example involves the use of a diabetes drug called metformin. The drug not only lowers the blood sugar level in people with type 2 diabetes but also improves the response of their cells to insulin.

In 2016, some interesting discoveries were presented at the Scientific Sessions meeting of the American Diabetes Association. Researchers at Tulane University reported that they had studied the health records of 6,000 people with diabetes. They found that the longer someone had taken metformin, the less likely they were to develop Alzheimer's disease or another type of dementia (and, interestingly, Parkinson's disease). People who had taken the medication for four years had one quarter the risk of developing Alzheimer's compared to people who used only supplemental insulin as a drug or insulin plus another medication to control blood sugar.

To complicate matters, there is some evidence that the link between insulin resistance and Alzheimer's disease goes or can go in the other direction—that is, a person first develops Alzheimer's and then later develops insulin resistance in the brain. Some researchers suspect that the link may be bidirectional.

An Alzheimer's Gene and Insulin Resistance

A recent report from the Mayo Clinic defines type 3 diabetes as insulin resistance in the brain instead of defining Alzheimer's as type 3 diabetes as some people do. According to the report, some scientists believe that the insulin resistance plays an important role in the cognition problems that appear in Alzheimer's disease.

The Mayo Clinic says that a gene variant (or allele) known as APOE4 is present in more than fifty percent of people with Alzheimer's and around twenty percent of the general population. Recent studies in mice showed that animals with APOE4 developed impaired insulin signaling, especially if they were older animals. In addition, a diet that was high in fat accelerated the development of insulin resistance in the brain of the animals.

Alzheimer's Disease: Protein and Perhaps Glucose Problems

Nature of the Link Between Insulin Resistance and Alzheimer's

Someone who researches the literature describing the link between insulin resistance and Alzheimer's disease will discover a lot of evidence supporting the link. The details of this link are unclear at the moment, however. Some possibilities include the following:

  • Insulin resistance in the body and brain can cause Alzheimer's disease.
  • Insulin resistance in the brain isn't the primary cause of Alzheimer's disease but can contribute to it and make it worse.
  • Alzheimer's disease can cause insulin resistance in the brain.
  • More than one of the above scenarios can occur, depending on the circumstances

Understanding the link is of far more than scientific interest. If the role of insulin resistance in Alzheimer's can be understood, it may be possible to treat or at least improve the symptoms of the disease as is currently possible in type 2 diabetes.

The researchers involved in the Mayo Clinic research described in the previous section of this article have performed a clinical study in which they administered an insulin nose spray to people with Alzheimer's disease. The results of the trial are not yet available. The researchers suspect that the spray will be most helpful for people without the harmful gene variant and that other drugs will need to be found for people with the variant.

Although more research and analysis is needed, I've seen enough reports to convince me of a link going from insulin resistance to an increased risk of Alzheimer's disease. Developing insulin resistance is always bad news, even if it doesn't cause dementia, so I'm going to work hard to avoid it.

References

© 2017 Linda Crampton

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    • AliciaC profile image
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      Linda Crampton 11 days ago from British Columbia, Canada

      I hope the insulin spray use is effective, too, Penny. It would be wonderful if it was!

    • Penny Sebring profile image

      Penny Sebring 11 days ago from Fort Collins

      Interesting information, I am eager to find out if the insulin nose spray is effective! I sure hope more research about this can lead to slowing or stopping this disease.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Thank you very much, Natalie. I appreciate your kindness.

    • Natalie Frank profile image

      Natalie Frank 2 weeks ago from Chicago, IL

      This is a fascinating article and very useful information. It's amazing how many links they are finding between different types of diseases that might be seemingly unrelated. Thanks for another wonderful article.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Hi, Nell. Yes, there is so much that we don't understand about the body. It's an amazing structure.

    • Nell Rose profile image

      Nell Rose 2 weeks ago from England

      I suppose it does make sense that there is a connection, my mum got a form of memory loss, not confirmed as alzheimers , but not connected to anything else. The fact is we just don't know so many things about our body and different effects it can have on other illnesses. Interesting read.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Hi, Dora. I hope your relative gets the help that she needs and that her condition improves. Thank you for the comment.

    • MsDora profile image

      Dora Weithers 2 weeks ago from The Caribbean

      The study revealing the link between insulin resistance and memory loss is very interesting to me. I've got a relative who has memory loss and getting worse, but the doctors refuse to diagnose the problem as Alzheimer's. She is diabetic also. Will share this information. Thanks again for another very helpful article.

    • AliciaC profile image
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      Linda Crampton 2 weeks ago from British Columbia, Canada

      Thank you very much, Nithya. I hope the research leads to cures for disease, too, as well as a better understanding of how the body works.

    • Vellur profile image

      Nithya Venkat 2 weeks ago from Dubai

      A great well-researched article clearly explained and easy to understand. Did not know about type 3c diabetes. Hope the research in the future helps to cure diabetes and Alzheimers.

    • AliciaC profile image
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      Linda Crampton 3 weeks ago from British Columbia, Canada

      Thank you very much, Kari. It will be interesting to see what else is discovered about a link between diabetes and Alzheimer's disease.

    • k@ri profile image

      Kari Poulsen 3 weeks ago from Ohio

      I have been hearing about type 3 diabetes lately, but this is the first I have heard of the link with Alzheimer's. It certainly makes sense. This article is very well written and informative. Thanks. :)

    • AliciaC profile image
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      Linda Crampton 3 weeks ago from British Columbia, Canada

      Thanks, Bill. I appreciate your comment very much, as I always do.

    • AliciaC profile image
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      Linda Crampton 3 weeks ago from British Columbia, Canada

      I agree, Devika—research can be very interesting. I hope the research described in this article leads to improved health for many people.

    • AliciaC profile image
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      Linda Crampton 3 weeks ago from British Columbia, Canada

      Thank you for the comment and for sharing the article, Chitrangada. I appreciate your visit.

    • billybuc profile image

      Bill Holland 3 weeks ago from Olympia, WA

      Really a very fascinating read, Linda. Thanks for all the research and for sharing your knowledge with us.

    • DDE profile image

      Devika Primić 3 weeks ago from Dubrovnik, Croatia

      An interesting hub on this disease and how it connects to another. Research really gets my mind traveling places. People have such issues with health in these categories and a lot more can be done to improve on it.

    • ChitrangadaSharan profile image

      Chitrangada Sharan 3 weeks ago from New Delhi, India

      Great article and a well researched information! I am aware about the Type 2 diabetes. Didn’t know how diabetes is related to different organs.

      I feel educated—Sharing it with someone, who needs to read this.

      Thank you for sharing your knowledge!

    • AliciaC profile image
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      Linda Crampton 3 weeks ago from British Columbia, Canada

      Hi, Jackie. I'm sorry that you have a tendency to develop high blood sugar, but on the other hand, I'm glad that you know this. It means that you can take steps to help the condition. Thank you very much for the comment.

    • AliciaC profile image
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      Linda Crampton 3 weeks ago from British Columbia, Canada

      Hi, Flourish. There is a lot about the brain and the body that is unknown. The facts that are being revealed are very interesting.

    • Jackie Lynnley profile image

      Jackie Lynnley 3 weeks ago from The Beautiful South

      What a powerful article! Who would have guessed and never had a clue myself for sure. My dad had diabetes, my mom Alzheimer's so my mind is all over the place in this. Was always strange to me too that mom had the sweet tooth. Lived to her 80s and never and sugar problems. If we just knew that thing that protects us from sugar!

      Hope they do get answers soon since I have a tendency to have mine run high off and on.

      Great work here!

    • FlourishAnyway profile image

      FlourishAnyway 3 weeks ago from USA

      I have read about this, as I read extensively on certain medical topics of interest. It’s interesting how diseases and conditions that seemingly had no connection do actually have a connection upon closer examination. There’s so much we don’t know, particularly about the brain. Thank you for shedding light on this for the masses.

    • AliciaC profile image
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      Linda Crampton 3 weeks ago from British Columbia, Canada

      Hi, Peg. Thanks for the comment. It's interesting that unexpected connections between different conditions are being discovered. The human body is complex and fascinating. I hope that the research leads to cures or at least better treatments for serious diseases very soon.

    • PegCole17 profile image

      Peg Cole 3 weeks ago from Dallas, Texas

      Quite a comprehensive bit of research and information here. I found the parts about the pancreas and its function to be quite interesting as I had a friend who was type 2 diabetic with uncontrolled glucose levels and she developed pancreatic cancer. Wonder if they will find a connection to that as well as to the Alzheimer's disease. Nice work Linda.