Diabetes Types and Insulin Resistance in Alzheimer's Disease
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.
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.
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 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 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.
- Type 1, type 2, and gestational diabetes information from the National Institutes of Health
- Type 3c diabetes is often misdiagnosed as type 2 from The Conversation
- Diabetes and Alzheimer's linked from the Mayo Clinic
- Insulin resistance and Alzheimer's disease risk from the Iowa State University
- Insulin resistance may prime the brain for Alzheimer's disease from the University of Wisconsin-Madison
- Metformin and Alzheimer's disease from Scientific American
- Alzheimer's gene linked to type 3 diabetes from the Mayo Clinic
Questions & Answers
© 2017 Linda Crampton