Opioids usage has become as common as taking daily vitamins. An opioid is a psychoactive chemical which diminishes the sensation of pain. The common name for opioids are painkillers. Whether over-the-counter or not painkillers are one of the most 
easily obtained drugs on the market. Today’s society relishes the abundance of these painkillers and continues to use them at an astonishing rate. Now having tolerance to pain would not be such a bad thing if it were not for the addicting nature of painkillers. For people suffering chronic pain over-the-counter painkillers such as morphine, vicodin and oxycontin are typically prescribed. However, strong painkillers such as these possess a high risk for the taker to become addicted to and dependent on the drugs.Famous celebrates such as Michael Jackson and Heath Ledger both fell victim to overdose caused by their dependence on opioids.
How can innocently taking a strong painkiller such as vicodin after a surgery turn into a dependence and in an extreme case, death? The answer lies in the chemistry of the brain. The pathway of pain begins in the peripheral nervous system with let’s say a cut on your finger. The signal travels from the receptors in the finger through the body to the spinal cord. The spinal cord then relays that signal to the brain where the signal is processed as pain. Speaking more in depth about the role of painkillers in the pain pathway, painkillers reduce the expression of a chemical called substance P. Substance P expresses itself at an exponential rate. Meaning that if one substance P is initially produced as the neuron fires that one substance P becomes two, which then 
becomes four, eight, sixteen and so on. Painkillers target the expression of substance P and reduces its production. However, inside the brain, as the neurons receive the opioid, a genetic transcription factor, CREB (cAMP response element-binding proteins), begins to code your genes to that painkiller. This means that the body becomes less receptive to the painkiller. Tolerance builds up and more dosage of the painkiller is required to obtain the same satisfaction as when the usage began. Along with the accumulation of tolerance, a person can develop an addiction to the pleasurable effects of the drugs. Addiction does not lie with the same genetic transcription factor as tolerance, instead a new genetic transcription factor, delta FosB, codes DNA for the craving of the painkiller. Death from overdose comes from the painkiller shutting down the sensitivity of the nervous system. Instead of turning off the body’s pain reception, overdose causes all reception in the brain and spinal cord to halt.
If the risks of addiction and overdose exist, why then are painkillers prescribed so often by doctors? One of the main reasons that doctors prescribe painkillers regularly is because they do not wish to lose their patients. If a doctor does not provide a patient with what they want, then there is a chance that the patient will leave to find a doctor who will give them what they desire. Therefore, doctors are almost forced into prescribing painkillers in order to keep their patients. Does fault solely lie with timid doctors afraid of losing patients? Society too plays a role in the overprescription of painkillers. Due to the abundance of pain medication people now-a-days are more likely to grab a bottle for the slightest pain. Pain tolerance is a factor to this. For example, I see myself as having a high pain tolerance and so rarely do I take pain medication. Because of this a small dosage usually does the job for me. If you look at my mother on the other hand, she has a very low pain tolerance. She not only takes pain medication more often but also needs more dosage to relieve that pain because she takes painkillers more often. Therefore, the fault of overly prescribed pain medications lies both with eager to please doctors and people with varying levels of pain tolerance. To place restrictions on the prescription of opioids would be a difficult manner as there is no universal chart for pain. Everyone experiences pain differently and as such there can be no definite way to administer the prescription of painkillers which is completely inclusive.
Hope for suppressing the addictive effects of prescription opioids?
When someone hears the word Vicadin or morphine they might often think about the negative effects of these drugs as they are extremely addictive and are also used recreationally for their psychotropic effects. A great number of people have been prescribed an opioid painkiller such as Vicadin, Codeine, or Oxycodone for various different reasons such as a post-surgery drug to ease the pain. Due to this fact, it is very important that our society knows just what is at risk when using these powerful painkillers. These painkillers are used enough in our society today that it’s not new to hear about opioids being very addicting and patients developing both a dependence and tolerance to the drug. Many people might ask, if it is known that using opioids can cause negative side effects such as dependence and tolerance, why are they still prescribed so frequently?
Opioids are such effective painkillers for many reasons. One main reason is that they have no analgesic pain ceiling, meaning they can block all pain. This is extremely important with serious surgeries that come with extreme pain during recovery. They are also used so frequently because they don’t have any negative effects on your liver, unlike the commonly used pain relievers like Advil.
Previous studies conducted in attempts to identify why opioids are so addictive have been focused on the dopamine system. This is mainly due to the fact that most addictive drugs increase the submission of dopamine, leading scientists to believe that the dopamine system would be involved in opioid addiction as well. However, in recent studies, scientists have been diving into the glutamate system as there has been recent evidence in the past five years that glutamate plays a roll in opioid addiction. Throughout the paper, “The role of glutamate and its receptors in mesocorticolimbic dopaminergic region in opioid addiction” many experiments are outlined that suggest glutamate is in fact an important piece to the puzzle describing opioid addiction.
Glutamate is the most abundant excitatory neurotransmitter in the brain. Glutamate binds to its glutamate receptors, ultimately opening a channel allowing ions to flow through and trigger an excitatory current. How is this abundance of glutamate and its respective receptors related to the development of an addiction to opioids?
After reading and analyzing the topic paper in class, it became very clear as to how glutamate is related to drug addiction. The paper did a great job laying out all of the specific pieces of evidence and just what they did to prove this relationship. One of the main studies that our paper focused on was the use of glutamate receptor antagonists, which essentially block the receptors from doing their job in excitation. There were many specific instances where scientists tested the effects of these glutamate receptor antagonists on addiction to opioids and they found that use of these antagonists successfully regulates drug tolerance and dependence.
These findings are very exciting as it would be ideal to be able to control the addiction of opioids, since they are extremely effective and prescribed so frequently. Although its seems as if scientists are on the right track as they explore glutamate receptor antagonists and their aid in preventing addiction, further research is needed due to the fact that glutamate receptors affect many different processes in the body and blocking them could cause effects other than suppressing addiction.
The Role of Glutamate in Opioid Addiction
This week in class we learned about opioid addiction and the role that glutamate plays in it. Opioids enjoy widespread use as pain relievers, some well known opioids are codeine and morphine. They are specifically used in order to treat acute pain, or in order to treat chronic, disabling pain that is associated with terminal diseases. Recently however, opioids are being used to treat non-malignant chronic pain, that is pain that is not associated with an illness or injury. This has lead to a growing number of people becoming addicted to opioids. For this reason it is very important that we understand what causes opioid addiction and how to prevent it.
The article that we have read for this week tells us that the brain pathway that is most responsible for addiction is the mesocorticolimbic dopaminergic pathway. The pathway is composed of the ventral tegmental area(VTA), the nucleus accumbens(NAc), the amygdala(AMY), and the medial prefrontal cortex(mPFC). These regions of the brain are responsible for the reward system of the brain, meaning that it reinforces certain actions once they are performed.
Now we can talk about how glutamate and its receptors play a role in opioid addiction. In the article it was said that the NMDA ionotropic receptor is very important in the development of addiction to opioids, as there are more NMDA receptors in the brains of morphine addicted rats. It was also shown in this paper that the substance MK801, which blocks the NMDA receptor upon binding with the receptor, can block the pain tolerance and physical dependence which opioid use can lead to, as well as the drug seeking behavior which drug addicted individuals display. It is also revealed in this paper that there are a number of specific metabotropic receptors which are linked to withdrawal symptoms in opioid addicts.
The article also investigates the signal transduction pathways which are responsible for opioid addiction. The release of calcium ions upon activation of the NMDA receptor leads to many different effects on the cell which all create withdrawal symptoms if the NMDA receptor is overstimulated. Another important pathway to consider is that of protein kinase C which upon the increase in the calcium concentration in the cell, the kinase promotes the creation of copies of itself and phosphorylates, that is attaches a phosphate to a G-protein which leads to desensitization when the G-protein in question is on an opioid receptor. Another important pathway to consider is the CREB pathway which is a common factor in many other cases of physical and psychological dependence. The application of opioids increases the concentration of CREB and related proteins and causes the copying of new proteins and leads to addiction. Lastly, the MAP kinase pathway which is important in rewarding response and behavioral sensitization which is brought on by the administration of psychostimulants.
The interaction of glutamate with other neurotransmitters was also explored in this article. It is said in the article that there is an interaction between opioid receptors and glutamate receptors which is vital to opioid dependence. It is also shown that there is a connection between glutamate and dopamine as it is shown that glutamate increases the amount of dopamine in NAc and increases the activity of dopaminergic neurons. It is also shown that activation of opioid receptors in the brain inhibited the activity of GABA neurons and inhibited the chemicals release. GABA normally inhibits dopamine, so the result of the opioid application is the increase of dopamine in the system. The article also briefly mentions substance P which the researchers writing this paper say that it has a relationship with glutamate, but that its role in opioid dependence still has to be studied.
In our small groups this week we primarily discussed changes in medical procedure, as in if we could ameliorate the concerns about addiction in the prescription of opioids. One very interesting thing we talked about was whether it would be better to just sever the nerve bringing pain sensation to the brain rather than worry about medication and the discussion gradually shifted to not over whether the severing of the nerve would be the practical thing to do, but what the implications would be if we gave this procedure to people. We talked about how pain is a valuable teacher, telling us about whether an object is dangerous or not, or whether we have been hurt or are hurting ourselves.
Morphine, Vicodin, and Oxycodeine: Why are opioids used when they are so addictive?
You may be familiar with several of the popular opioid medications (morphine, vicodin, and oxycodone) prescribed to people with severe pain. Also, you may have heard about the serious addictive effects which may result from taking these drugs. However, two questions that seem to never be asked are: 1) why are these drugs so addictive? and 2)if they are so addictive why to doctors continue prescribing these opioid medications?. As part of this week’s discussion, we attempted to analyze the addictive nature of opioid drugs and understand why we continue to use such drugs even though they are highly addictive.
The article we looked at focused on a molecule called glutamate, which is found in most part brain, and its involvement in the opioid addiction mystery. It turns out glutamate may play a bigger role in addiction than previously thought. Since glutamate is one of the most abundant neurotransmitters in the brain, it is found in many different areas including the ventral tegmental area and nucleus accumbens which are believed to play a prominent role in addiction. When opioids are used, more glutamate neurotransmitters are released and interact through many complex pathways causing an increase in dopamine, which is the neurotransmitter associated with the reward. This causes the body to think it is being rewarded for taking opioids. Additionally, when glutamate binds with its own receptors it can cause addiction and withdrawal-like feelings by acting through many different biological pathways. However, I would like to note addiction is much more complicated than this and more research is needed to understand addiction better.1
This leads us to the question why do we use opioid medications if they are so addictive? As discussed in class the key reason seems to be the effectiveness of stopping pain. Besides opioid drugs, the other common type of pain killers are non-steroidal anti-inflammatory drugs (NSAIDS) which includes Advil and Aleve; acetaminophens likes Tylenol; and aspirin. All three pain killers act by stopping an enzyme (called cyclooxygenase or COX) found throughout the body which is responsible for feeling inflammation and pain. NSAIDS and aspirin block this enzyme in the areas outside the brain while acetaminophens block the enzyme in the brain. Although these drugs are successful, they come with side-effects such as liver and kidney damage and blood thinning after extended periods of time. 2 However, opioid medications act in a different way therefore making them excellent pain relievers. Opioids change the perception of pain by working on the spinal cord and the brain. Opioids pain killing characteristic works by closing and opening a variety of channels in the brain resulting in a reduction of the brains ability to feel pain. Closing and opening these particular channels are more effective at reducing pain than by stopping the COX enzyme either in the brain or the peripheries. Additionally, as a result of changing channels instead of stopping an enzyme, opioid usage do not have many of the long-term side-effects associated with the other pain killers. However, since they interact with channels in the brain addiction is much more prevalent than with the other drugs.3
Therefore to summarize, opioid medications such as morphine, vicodin, and oxycodone acts in such a way that when taken glutamate is released and through several pathways causes dopamine to be released. This results in a feeling of reward. Additionally, when excess glutamate binds to certain receptors in the brain one feels addictive and withdrawal-like feelings. However, the reason why opioids medications continue to be used is because they are more affective at reducing pain and contain fewer physical side-effects as compared to NSAIDS, acetaminophens, and aspirin.
Finally, this raises questions about what should be done with opioid medications. Would you rather live a life without pain but have the possibility of becoming addicted to your medication or would you rather live with pain but know you will not be overcome by the psychology effects of addiction? Or should scientists continue expensive research in the hopes of stopping the addictive nature of the opioid. There seems to be not right answer but it does appear opioid medications are going to remain in our society for the foreseeable future.
Sources:
1) http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000802/
2)http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004928/
3)http://www.webmd.com/pain-management/opioid-analgesics-for-chronic-pain
Glutamate antagonists: the answer for opioid dependence?
In 3400 BC, the Sumerians first cultivated the opium poppy plant. Since its discovery, opiates have been used medicinally to relieve pain, and more recently, to suppress coughing in patients with a “dry cough”. However, as with most pharmaceuticals, negative side effects exist to the continuous use of opiates: tolerance and dependence. The physical and psychological dependence that results from opiate use adversely impacts society. These factors make it dangerous for physicians to loosely prescribe opiates to patients (although this does not mean it doesn’t happen).
For many years, dopamine has been the focus for scientists when researching the effects of addictive drugs, though more recently, this focus has transitioned to include glutamate’s (another excitatory neurotransmitter) role in drug addiction. Glutamate exaggerates the withdrawal symptoms of opioid dependence by binding its receptors, specifically ionotropic receptors.
Learning point: There are two functionally different types of receptors that bind neurotransmitters: ionotropic and metabotropic. Ionotropic receptors are channels themselves and open in response to a neurotransmitter (i.e. glutamate). This causes an influx of ions (ionotropic) that either excites or inhibits the cell, depending on the ion moving through the channel. Metabotropic receptors are much slower than ionotropic receptors and act more indirectly in the cell. A series of proteins and second messengers interact with each other to signal a cascade of events in response to a neurotransmitter binding a metabotropic receptor.
Accumulating evidence shows that antagonists of ionotropic receptors (iGluRs) can attenuate the withdrawal symptoms of opioid dependence. One specific antagonist of interest to scientists is called MK-801. It is a glutamate antagonist that acts on NMDA receptors and protects against excitotoxicity (excessive stimulation of the neuron). Researchers are hopeful that MK-801 could suppress the psychotropic effects of prescription opiates. This is of great importance to researchers as it offers a potential way to decrease the negative side effects of opiate use. What a difference it would make if taking prescription opiates did not lead to dependence and moreover, illegal activity. Illegal activity? It is not uncommon for patients to sell their prescription drugs, such as morphine or codeine, to dependent users for a little extra cash. This is because those who are addicted to prescription opiates crave the drug due to its psychotropic effects and the withdrawal symptoms the person feels in the absence of the drug.
The ability to prescribe opiate analgesics (pain relievers) without the addictive effects (or any of the unnecessary side effects for that matter) is ideal. The illicit sale of opiates would significantly go down if this were possible. Of course, there would always be a black market sale of opiates, but at least users would not be able to obtain the drug so easily. Furthermore, the number of users addicted to opiates would drop considerably as the only people who would be addicted to opiates would be those who acquired opiates via the black market.
It is of upmost importance that scientists continue to investigate the use of glutamate antagonists as a means to subdue the negative effects associated with opiate use. It would be in the best interest of everybody to continue research in this arena. Patients would be safer, doctors would be relieved of the pressure to prescribe opiates, the community would become safer, and the stigma of prescription opiates would eventually be diminished.
Vicadin! Codeine! Oxyconton! Oh My!
You may (or may not) have heard of a class of drugs called opioids. These drugs are commonly prescribed to patients to relieve their pain after a surgery or if they are experience a chronic pain. These drugs are fantastic (as most drugs are) at making the patient feel great, however, they have one serious side effect; they are ridiculously addicting. This begs the question, “Should these drugs be used?” They are highly effective at treating the pain, but are the risks of addiction worth it? Is there something we can do to get rid of the addiction?
If you were to ask me my opinion on this issue, I would tell you to stop using opioids to treat pain. “But Brandon, why wouldn’t you use them in moderation? Or do research to relieve the side effects?” Right now, in the medical field, there are “regulations” on the prescription of opioids, but it still seems to have no effect on the problem as doctors are still handing them out like candy, and people receive an excess of what they actually need and could sell them on the streets to addicts. Even if one doctor turned down your request for a prescription, you could just as easily go and see another doctor and ask them. All in all, I don’t feel that regulation is a good solution to the problem at hand. As far as the research goes, I do see this as a possibility. There is currently research being done on opioid receptor antagonists and how they prevent the addictive property of these drugs, but in the end is it really worth the effort? To me, I see much more prevalent areas of research among medicine and drugs rather than working with pain killers. As I see it, pain killers are for wimps. Before you get mad, let me explain myself. Think back to a time way back when people didn’t go to the doctor to cure their minor pains. They weren’t prescribed opioids and thus didn’t get addicted; they just sucked it up and dealt with their pain. For more major pains, we have other pain killers which aren’t addicting such as NSAIDS (advil or aleve) which would help the patient cope with the pain without addiction side effects, which to me is worse than the side effects of NSAIDS. Therefore, I feel our government research money can be spent more responsibly.
As you can see, opioids can have great success in treating our pain, but in my opinion, we should just stop using them due to their nasty addictive nature and switch to using a “safer” pain killer option such as NSAIDS.
Pill Nation?!
In the article which we read for this week, the authors investigated the roles of glutamate and its receptors play in opioid addiction. When people hear the word “opioid”, it is thought as the illegal drugs, such as opium alkaloid, morphine, and semi-synthetic alkaloid derivative, heroin. But in the world of medicine, opioid plays an important role as pain killer, which is often prescribed to people who suffer from severe pains. Most of these pain pills are classified as the semi-synthetic alkaloid derivatives, the same classification as heroin. Oxycodone and hydrocodone are two of these pain killers that are often prescribed by doctors.
Although opioid drugs do a great job relieving pain, just like heroin, they are also addictive and may be very hard to quit. And people who depend on these drugs often need to go through a long and painful withdrawal. Therefore, the prescriptions and the usage of the drug by doctors have become very important. On Wednesday, Annika talked to us about the process of prescribing opioids and the “regulations” on it. But just regulations don’t seem to be enough. In fact, prescription drug abuse has already become a severe problem in the United States. I have always enjoyed National Geographic Channel’s documentary series, one of my favorites is the show called “Drugs, Inc.” And one of its episode deals with the problems of prescription drug abuse. This film interviewed users, doctors, dealers, and the law enforcements, and went into details about this industry from different perspectives. According to this documentary, nearly 1.9 million Americans are addicted to prescription pain pills, ten thousand newborns were born with addiction each year, and dealers and rouge doctors make millions off this black market trade.
Since the regulations have already failed us, another strategy needs to be played. There are many researches being conducted on opioid receptor antagonists and how they may help avoiding the addictive characteristics of these drugs. And some of them have shown promising results. But in my opinion, getting rid of the addictive characteristics of these drugs only helps with dependence physically. Unfortunately, that is not the only part of addiction. In psychology, we learned about the concept of classical conditioning, which is basically a form of learning in which the conditioned stimulus comes to signal the occurrence of the unconditioned stimulus. In the case of pain pills, by taking the pills and removing the pain of our body, we are essentially conditioning ourselves to associate the pills with the removal of our pain (negative reinforcement). This applies to not only the opioids but all kinds of pain killers (NSAIDS, Acetometaphin, Aspirin), which means they may all be addicting if used incorrectly.
After all, pain is very subjective, difficult to measure and everybody experiences it differently. All in all, I appreciate/respect what the researchers are doing with the opioids, and I really hope it could be completed. But the real problem I see here is the prescription and usage of the pain pills by the doctors as well as the patients.
To watch “Drugs, Inc.- Pill Nation” http://www.youtube.com/watch?v=AG3qM1NXRXA&feature=related
Opioids and Addiction
I have been hearing more and more these days that doctors are handing out high-potency pain killers like they are candy and I have been wondering why, when these drugs have a history of being so addicting, doctors are so keen to prescribe then for even the most menial of pains. The drugs I am talking about are the opioids: morphine, hydrocodone, codeine…heroin, the list goes on and on. Derived from the opium plant, these drugs are the pinnacle of analgesic and anesthetic drugs, with morphine as the baseline that most analgesics are compared to. It is the fact they do their job so well that makes them so addicting. So again I ask why are they still being used?
In this weeks discussion, we talked on what we thought about how easy it was to get opioids and a few ways we thought opioids research could go in order to keep the analgesic effect but lessen or eliminate the addicting effects. Opioids have strict regulations on what factors illicit their prescription but it seems that the enforcement of their distribution is on the weak side. What one person brought up was that if a patient goes into the doctor and ends up coming back for the same exact problem, the insurance can deem the first visit ineffective in a way and refuse to pay the cost. So doctors end up “over-prescribing” in a way to make sure the patient doesn’t return for the same problem. This brought us to talking about what can be done to reduce or eliminate the dependency/addiction issue. Analgesic/anesthetic drugs are a dangerous kind of drug because even if you don’t develop a dependence for them, you can still get addicted to them. What I mean is that even if the drug was made so that you didn’t develop a resistance and you could stop taking it with no side effects, the fact that it rids you of pain and makes you feel good makes it pleasurable to take.
Another question brought up was how can addiction be dealt with in a mind over matter approach. I think that the brain (mind) has the biggest role in addiction because addiction is all about dopamine release in the brain. Dopamine is the “feel good” chemical in the brain that’s in charge of rewards and such. It’s that feeling you get when you have your favorite food or when you are swarmed by a mob of playful puppies. It’s your bodies signal of what you like and what you don’t like. Back to the addiction aspect of dopamine. When you take a drug, such as heroin, dopamine is released in great quantities which results in the euphoric effects. As you continue to take it, your body compensates for the increase in dopamine release, resulting in you having to take more to feel the same effects. Now fast-forward to when you stop taking the drug. You start going through withdrawals which is what happens when you have that constant inflow of dopamine and all of a sudden its gone. You feel absolutely dead and you just can’t function without more of the drug. Could you avoid the withdrawals by conditioning your brain to not need the drug anymore? Could you associate the drug with something you don’t like and replace it with something that was not as bad for you and easier to get?
I’ll try to explain what I am talking about. Say you are taking heroin. You are addicted but want to quit and know you should. Can you start doing something not pleasurable while taking heroin to in turn make taking heroin not pleasurable? Then can you substitute heroin with something not illegal or harmful but still pleasurable so you can kick the heroin habit? I think it is possible but of course the only way to know is to actually do it but that may easier said then done.
Research Suggests Great Defense from Alzheimer's Disease could be the Dinner Plate
“What would you like to order today?” “I want two number ones, a number six, a large side of fries and a shake.” “Would you like some insulin with that?” “Insulin?”
Most who hear the word insulin think about Diabetes; perhaps have had a friend or family member who takes insulin, either the pill form or a continuous pump, and checks blood sugars before and after a meal. However, for those who do not know, Insulin is a hormone produced by the body to help regulate energy in cells throughout the body. It is involved in how the cells intake glucose, the most prevalent sugar used in the body, and therefore keeps our bodies processing normally.
This week insulin’s role in the brain was brought to light for the neurochemistry class, because research has shown a correlation between the body’s use and misuse of insulin to the symptoms of the neurodegenerative disease know as Alzheimer’s. The symptoms such as dying brain cells as well as plaques and tangles in the brain.
The outside of brain cells are covered with docking stations specialized to accept insulin; when insulin attaches itself to these receptors the cell undergoes changes that allow glucose to enter from the outside and other cellular processes result from insulin’s binding to the cell. These other processes have a profound effect of the life of the brain cell, as well as the brain’s overall health. One of the pathways after insulin binding is the an enzyme (Protein Kinase B) that stops another enzyme (Glycogen Synthase Kinase, GSK) from becoming more active in the cell’s functions than it is meant to be. The enzyme GSK, if not under control has been found to have involvement in the processes that result in the tangles in brain, as well as the buildup of plaques.
Another important pathway after insulin binding that is important for the activation of an enzyme (BAD, an antagonist to cellular apoptosis) that communicates with the cell for the prevention of cell death. As a result more brain cells stay alive which protects an individual’s mental health.
Now, where does the dinner plate come in?
Unhealthy eating and lack of physical activity dramatically increases a person’s chances of contracting of Diabetes, specifically type 2. Type 2 Diabetes, is when your body does not produce enough insulin, or the number of docking stations on the cell for insulin is low. This lack of docking stations, also called insulin resistance, slows the processes of brain cells toward defending themselves from death, and from creating plaques and tangles. This all increases the early symptoms of brain diseases like Alzheimer’s.
The next time the dinner bell happens to ring at your house, take a moment and ponder about how sneaking some healthy foods might help keep your family physically healthy; while at the same time protect your loved ones future mental health.
Sources:
http://www.sciencedirect.com/science/article/pii/S1043276005000093#bib83
Super-size Nation, Super-size Problems
The modern trend of increasing rates of obesity is a cause of concern for many. The effects of obesity range from emotional problems such as low self-esteem and bullying to health problems including cardio-pulmonary stress and diabetes mellitus (DM). Recent research points to results indicating that obesity may also be involved with mental problems such as dementia and Alzheimer’s disease (AD).
Much of this conversation begins with insulin. Type II diabetes is a form of DM that occurs when the body begins to exhibit characteristics of insulin resistance. The body may also stop producing insulin properly. Insulin is needed to bring blood sugar into cells to be used as an energy source. Once called adult-onset diabetes, views about this disease are changing because it is now developing at a much younger age than previously observed. View the Centers for Disease Control and Prevention’s website for more information on type II diabetes and children: http://www.cdc.gov/diabetes/projects/cda2.htm
In addition to cell energy demands, insulin functions in cell signaling. When insulin is recognized by a receptor on the cell membrane, a chain reaction phosphorylation cascade occurs. Energy is used to continue the signaling pathway. At the end of the signaling process, gene expression can be influenced. Cell proliferation and growth is also a result. A blockade in this pathway, associated with aging, leads to cell death. Neuronal cell death is one characteristic of AD.
As early as 1999 a study in the Netherlands showed that DM was a risk factor associated with dementia. Over 6000 adults aged 55 and over participated in the Rotterdam Study, which included complete health screenings and follow-up either in person or using the individual’s health record. They found that the percent of dementia in that population that could be traced back to DM was 8.8% and most of those exhibiting dementia were also diagnosed with AD (Ott A, Stolk RP, Hofman A, et al. Diabetes mellitus and risk of dementia: the Rotterdarm Study. Neurology. 1999; 53: 1907–9.). Those with newly diagnosed or untreated diabetes had a lower risk factor for dementia than those that were insulin treated. In sum, those with more severe diabetes had a greater risk of developing dementia.
If type II diabetes is developing in adolescence rather than middle age, what does this say about Alzheimer’s disease? A trend often referred to as an “epidemic” by popular usage and the media, obesity is influencing health on a variety of fronts. Type II diabetes is strongly associated with obesity and so, therefore, is insulin. Findings of type II diabetes in children rather than middle aged adults is a twenty, thirty, even forty or more year advance in the disease. Could this “fast-forward” in deterioration translate to diseases that are associated with DM, such as AD? Granted, DM is a risk factor associated with AD, not a necessary cause, but this alarming trend may have far-reaching effects that cannot yet be foreseen.