The Outstretching Reaches of Diabetes

            Diabetes is a very complex disorder that is made up of several linking components stretching across a wide variety of systems. These systems cover everything from physiological components, to psychosocial behavioral issues, and even a significant effect on the economy. These diverse topics when seen at a glance may seem completely unrelated, but when we get down to the specifics it all traces back to one root cause, diabetes. If we take a closer look, it boils down to the abuse of one single molecule, glucose. In today’s world it’s all about connections, diabetes exemplifies this need to great extent.

            Before we can discuss diabetes’ connections, we must first understand the basic mechanism behind how it works. Diabetes is caused from having high blood sugar for long periods of time. The root pathway behind this all ruminates from insulin intolerance; where the body loses its capacity to make insulin. Without insulin glucose cannot be transported to your cells efficiently and tends to build up in your blood stream. This buildup of glucose is what connects diabetes to the diverse topics we will be discussing today.

            Diabetes has many connections with physiological components and disorders within the human body. The main items I want to talk about is how diabetes connects to cancer, blindness, and, kidney failure.  The mechanism for how cancer comes from diabetes is all in the sugar and insulin. The excess of the two aid in tumor growth: sugar as a source of energy fuel source and insulin as a growth factor. Cancer cells practically run off of glucose so having excess sugars in your blood is like adding oxygen to fire. Cancer cells also have insulin receptors on their surfaces. This is the key to the cancers success! When cancer cells captures insulin it gains three benefits. Insulin encourages cell growth and discourages cell death, bolstering the proliferation of cancer cells. At the same time, studies suggest that insulin makes cancer cells more invasive and more likely to spread. This invasiveness is why our body can’t stop it effectively. The cancer cells spread so quickly that our immune system cannot fight them off at the same rate that they spread. Forms of retinopathy (blindness) follows a similar physiological pathway in which high glucose levels cause changes to retinal blood vessels that can cause them to bleed or leak fluid, distorting vision. How this happens in a nutshell is you develop high blood glucose levels (from diabetes); this escalated blood glucose levels cause glycation to your RBC’s and thus make it harder to push blood through your arteries, veins, and capillaries. Over time the capillaries in and near the retina began to expand and weaken (microaneurysms) from the excess blood glucose and glycation. The microaneurysms allow RBC’s to leak into the retina (usually on the outside) and cause blurred or a narrower field of vision and without treatment blindness. Nephropathy (kidney failure) can be induced by diabetes. Basically high levels of blood sugar make the kidneys filter too much blood. All this extra work is hard on the filters and after many years, they start to leak and useful protein is lost in the urine. So why is this important (other than you need your kidneys to survive without extensive dialysis treatments). The proteins lost in your urine (micro or macroalbuminuria) are obviously not getting to your cells to carry out their many vital functions for day to day life.

            Diabetes has its connections with psychosocial and behavioral issues. Diabetes has major effects on the brain and its functions. The main thing that diabetes effects is hormone imbalance; primarily dealing with dopamine and norepinephrine. My main focus on diabetes effects on the brain deals more with behavioral disorders; in specific, schizophrenia and ADHD.  In schizophrenia again it’s the insulin regulation that is messing everything up. See insulin doesn’t just regulate glucose it also regulates dopamine to the brain. The insulin overabundance restricts the dopamine regulation and free flow of norepinephrine in the prefrontal cortex of the brain (responsible for cognitive functions). This lack of dopamine and too much norepinephrine allows for an overabundance of the NET transmitter protein. What NET does is it sucks away all of the dopamine and converts it to norepinephrine. So in a nutshell the insulin causes an overabundance in the NET transmitter protein and results in hormone imbalance causing schizophrenic behavior. With ADHD it is almost exactly the same problem. People with Type 2 Diabetes show ADHD like behaviors depending on their blood glucose levels (too high or too low). Low blood glucose can cause inattention and impulsivity, and high blood glucose can cause restlessness and irritability. This irritability is caused by malfunctions of neurotransmitters that control both dopamine and norepinephrine.

            We have talked about both the physiological and behavioral associations of diabetes and now we are going to talk about its effects on society and the economy. A study was conducted to update the previous estimates of the costs and burdens diabetes puts on the U.S. population. To more adequately estimate these costs they used the current U.S. Census Bureau (for the population) and a diabetes prevalence approach by sampling the population by different categories to include: age, ethnicity, sex, insurance status, and home of residence (whether or not it is in a nursing home or not). Throughout the study they were able to break down the cost burdens to show that diabetes costs the nation $245 billion dollars annually; of that $176 billion is from direct healthcare while the other $69 billion results from loss of productivity of the American people. This shows that diabetes prevalence in the U.S. is rising about 5.2% annually (specifically a 27% rise from 2007-2012) and that people with diabetes pay 2.3 times more annually for healthcare than people without.

            In today’s world it’s all about connections. As we have seen diabetes is a very complex disorder that is made up of several linking components stretching across a wide variety of systems. It has vast effects on physiological components, psychosocial behavioral issues, and even the economy. At a glance they may seem completely unrelated, but when we get down to the specifics it all traces back to one root cause, diabetes. If we take a closer look, it boils down to the abuse of one single molecule, glucose. Diabetes exemplifies this need and power to connect at a great extent.

           

           

           

            

Levi Myers

BIO 4500

Pathology of Diabetes

The first time I took ideas from two reading places was when I made the connection between epigenetics and the disease state of diabetes from class reading. In the epigenetic reading I learned a few key concepts that I was able to connect with diabetes that helped me to understand the disease a bit better. The first of these was how histone modification is responsible for the different cell products available in the many cell types. These histone modifications alter how tightly the DNA is bound. The tighter the nucleosomes are bundled the less transcriptionally active the segment of DNA will be. I then applied this concept to a few of the common problem mechanisms involved with diabetes. First was how pancreatic beta cells produce insulin. These cells have segments of the DNA that code for the hormone insulin that is transcriptionally active. One of the problems that is common in diabetes is that the beta cells get overworked and cease to produce the needed amount of insulin. The other location where gene control would be important is in the expression of the glut transporters. In a normal cell insulin binds and causes the glut transporters to be inserted into the membrane of the cell so the glucose can be absorbed. From my reading I learned that one of the mechanisms of insulin resistance is that even thought there is insulin in the blood stream when it binds to the insulin receptor there is not enough of the glut transporter to absorb the glucose in the blood stream. This leads to a few of the common symptoms of diabetes including hypersinsulemia, and hyperglycemia. I connected this with epigenetics, as there must be a connection to the diabetic disease state and how less glut transporter is produced. From this I also learned that all disease could be taken down to the cellular levels.

For my second place where I was able to make connection through my reading I was studying advanced glycolation products and pathology of diabetes. These products are formed from the high levels of glucose in the blood. Also important is the length of time the blood glucose is elevated. When this combination of extended high glucose levels is present it leads to glycolated products. One of these is hemoglobin. In this case there are glucose molecules that bind to one of the subunits on hemoglobin. I had previously known of these products but was not able to make the connection to how they were harmful. From my reading there were two ideas that I learned that I had never heard of. The first was that AGEs have a specific receptor that they bind to called RAGE. This receptor when bound leads to the expression of growth factors and other harmful products that increase the coagulation of endothelial cells and lead to the deposition of basement membrane material. I also learned about how glucose bind to different types of collagen and this leads to interactions with proteins in the blood and lead to much of the vascular abnormalities see in patients with diabetes such as atherosclerosis, retinopathy, and decreased elasticity of vessels. This specifically applied to bigger vessels and how by this crosslinking of collagen the vessel walls become less elastic. When this happens the vessels are less likely to be able to accommodate high-pressure situations. This leads to small tears in the lining of the vessel and lead to atherosclerosis and other vasculature problem. Common also in people that type 2 diabetes is hyperlipidemia. I was able to connect this with the RAGE receptor and how it releases factors that lead to increased cell adhesion. This in combination with these tears in vessel walls leads to the deposition of fat cells at the site of injury. This leads to the buildup of macrophages and other cells that slowly lead to the occlusion of smaller vessels or in sever cases an unstable angina. These can break off from the vessel wall and turn into a pulmonary embolus or even stroke based on where the embolus lands. Mostly I was able to connect a bunch of different diseases that I had learned with understanding a few of the physiological mechanisms regarding diabetes.

            For my third place where I was able to connect multiple ideas from my reading I connected with what other things have been rising at the same time as diabetes specifically the last 50 years.  There were a few things that came to mind. The first thing was as there was an increase in diabetes there was an increase in the marketability and consumption of fast food in the United States. This is by no means causation, however it is an interesting correlation. This has led to an increased availability of these high calorie foods and also the continued development of the idea that time is money. . The second is how this disease has grown in concert with music and technology. These things have tended to get more cerebral as time progresses and there is a turning into the mind that I find to be troubling. While reading an article I came across the term screen time. This was being used in relation to the total time that was spent by an individual on anything with a screen. This value has also been increasing along with the diabetes epidemic.

            In all I was able to learn a lot from my reading and was able to connect more than I thought that I would be able to.

Diabetes of Knowledge and Education

Diabetes Knowledge and Education

Over the course of this class, we have discussed and researched Diabetes. Diabetes is a very common disease that has two forms, Type 1 and Type 2. Type 1 Diabetes is a genetic autoimmune disease that attacks the beta cells of the pancreas. Type 2 Diabetes, the more common form, is the result of consistently overworking the beta cells that produce insulin, which causes the beta cells to malfunction. This specific type also induces insulin resistance that makes the cells immune to the hormone (“Facts about Type 2”). Multiple connections have been made to Diabetes in the past few weeks such as cancer, economic data, and pathway functions on the biological side of things. Through these connection, we can see how impactful Diabetes is to different markets and areas of interest. For example, Diabetes serves as a huge centerpiece in pharmaceutical businesses that produce insulin for blood glucose monitoring. As a common disease, many people like myself have heard about Diabetes. Although Diabetes is a common health disease, people don’t necessarily know the specific details of the disease. Personally, I thought Diabetes was a minor health disease in which there were no seriously complications or health risks associated with it. However, this was very naïve to think. After studying the disease, this lead me to think about other people who might not know about the disease, how many people have been affected by unawareness, and benefits of education on Diabetes and possible preventative methods.

In Class, we discussed an article about the GSK3 protein. The protein was a major regulator in pancreas cell production which inhibited cell growth when activated, activating as a modulator of beta cell production (Mussmann et al., 2007). Not only was this a monumental discovery in developing Diabetes treatment, but it also shows how much we, as a scientific community, know about Diabetes. Although we may know the causes and potential dangers with the disease, we don’t know much about the links to other diseases or about how to treat a disorder like this. Much research has gone into Diabetes and links to different pathways have been discovered, however, there is always new data and pathways that can be connected to Diabetes. The GSK3 protein shows how much we think we know about Diabetes, but new discoveries could lead to better advances in treatment procedures. Instead of thinking we know a lot about Diabetes, we need to be realistic in that there is more that we need to learn about the disease and different mechanisms involved until we find a suitable treatment.

While researching about Diabetes, I came across a story of a diabetic lady that had mistreatment by health professionals. In one of her stories the doctor did not take into account the patients Diabetes in his diagnosis, which ended up being a contributor to her illness. In another case, the nurses did not know how to properly handle diabetic patient situations or how to carefully monitor their blood glucose levels. Although most nurses should know how to properly deal and assess diabetic patients, there are the few that don’t which raises concern. Being at the forefront of the medical field, nurses need to be able to do, at the very least, common disease treatment and how to manage patients with different health conditions (“Scary diabetic hospital stories,” 2010). Like I said before, most nurses are capable of doing these things; however, maybe the new nurses or ones who don’t normally handle situations like these are depended on. Either way, improper care of a patient with a health difficulty needs to be treated carefully to avoid potential harmful side effects such as hypoglycemia. In these cases of the diabetic lady, she knew more about how to handle her heath than the professionals, which is something that is somewhat ironic.

People knowledgeable about Diabetes resulted in better care of themselves and overall health than others who were unknowledgeable (Chavan et al., 2015). During this study, about 300 diabetic patients were evaluated on their knowledge of Diabetes. Only one-fifth of the patients knew a “good-amount” about Diabetes whereas the majority of the patients knew very little or decent amounts. The results showed that even though most patients in the study were diabetic or years, they still didn’t know how to properly take care of themselves due to the lack of knowledge about the disease. Education about the disease is crucial in making sure the patient is also taking care of themselves. In this case, people who were diagnosed with Diabetes did not know about the disease and probably thought it was very minor and unimportant. Just like me, these people probably thought the disease was no big deal because of the amount of other people diagnosed with Diabetes, its commonality. Speaking about Diabetes and educating people about what the Disease actually is and the potential issues that come about it could help administer better cooperation between physician and patient in treating the disease. This “comfort” of Diabetes in those who don’t think it is a big health issue is dangerous because someone wouldn’t care if they were diagnosed with Diabetes or not. Overall, proper education of the disease could help in better awareness of the other potential harm and causes that the disease may entail.

With the different aspects of Diabetes and those involved in treatments, some people like myself don’t know too much about the disease. This is particularly a result of the lack of education and information about the common disease. Although the disease is very common, there are potentially dangerous symptoms if not properly cared for. Especially with the study of Chavan et al. (2015) suggesting that some people who were diagnosed with Diabetes didn’t know much about the disease. Overall, Diabetes is interrelated to several different health problems and concerns, which means that the healthcare professionals need to be updated on proper treatments for the disease, as well as how to handle certain situations if a patient is diabetic.

References

Chavan, G. M., Waghachavare, V. B., Gore, A. D., Chavan, V. M., Dhobale, R. V., & Dhumale, G. B. (2015). Knowledge about diabetes and relationship between compliance to the management among the diabetic patients from Rural Area of Sangli District, Maharashtra, India. Journal Of Family Medicine & Primary Care, 4(3), 439-443. doi:10.4103/2249-4863.161349

Facts about Type 2. (2013, August 1). Retrieved September 23, 2016, from http://www.diabetes.org/diabetes-basics/type-2/facts-about-type-2.html

Mussmann R, Geese M, Austen M, et al. Inhibition of GSK3 Promotes Replication and Survival of Pancreatic Beta Cells. Journal Of Biological Chemistry [serial online]. April 20, 2007;282(16):12030-12037. Available from: Academic Search Premier, Ipswich, MA. Accessed September 24, 2016.

Scary diabetic hospital stories. (2010, April 18). Retrieved September 23, 2016, from http://thegirlsguidetodiabetes.com/2010/04/18/scary-diabetic-hospital-stories/

History of Diabetes and Where to go Next

Kyle Javenes

BIOL-4500

History of Diabetes and Where to go Next

The history of disease is often overlooked by many individuals. Looking at where we have built off of can be quite inspirational, especially when looking at more recent history. It can tell us how diseases can evolve biologically, but also how they change our culture. For example, we used to refer to sailors as “limeys”. This cultural norm was caused by the finding of scurvy being prevented by citrus fruits and sailors were the population most at risk. When they started consuming more of these fruits the name came with it.  More relevant though would be the change in naming for diabetes. We used to say type 2 diabetes was adult onset diabetes, but now we see children with the same etiology. This dismisses the prior naming and we settle on calling it type 2. Disease can leave a huge impact on the world we live, whether historically, presently, and or in our futures.

The first recorded mention of what we know to be diabetes is over 3500 years ago in Egypt by Hesy-ra (McCoy, 2009). He described the urine as sweet, but aside from that nothing about treatment was mentioned. This isn’t meant to say no one was trying to understand the disease, but the options weren’t great. In 150 AD a Greek physician by the name of Arateus said that diabetes is “the melting down of flesh and limbs into urine” (McCoy, 2009). This was a fairly accurate description of what happened to people until 1921 when the first insulin treatment was done by Banting and colleagues (ADA, 2014). There is still a lot that happened though prior to this huge success, but in comparison they are small changes. In 1675 it was no longer referred to as diabetes, but diabetes mellitus (which translates to “siphon honey”) ( (McCoy, 2009). What would have driven this change? Likely “water tasters” had something to do with this because they were often sampling the urine for their work. In 1776 Matthew Dobson measured for glucose contents in the urine and found higher levels in diabetics (Polonsky, 2012). This identified what created that sweet taste in the urine. Knowing what was in the urine set up for some chemical testing and in the early 1800s just this happened putting water tasters out of business to some extent.

By 1812 the New England Journal of Medicine and Surgery established diabetes as a disease (Polonsky, 2012). The world doesn’t quite revolve around this journal though as treatments were already being given out prior to that by clinicians who recognized it as a disease. In the 1700s diabetes patients started to receive recommendations on changing diet and exercise (McCoy, 2009). This has had some lasting impacts in how we treat diabetics today even. The primary recommendation was to not consume sugary foods and shift the diet over to largely fats and proteins. There was another recommendation though which was to overload on carbs.  Treatments were starting to be developed more and more at this point. In 1889 someone thought to remove a dog’s pancreas and see how they died (McCoy, 2009). This is eerily similar to the concept of gene knockouts, but a bit bigger. Well they found out that it was by diabetes. We would not be able to have done this in today’s time. Just like how our understanding of diseases has grown so has our understanding of ethics and this hinders many developments in science to a more morally correct model.

Some situations arise for researchers to make great use out of. Around the time of WW1 Apollinaire found that his diabetic patients’ symptoms were alleviating when they were starving (McCoy, 2009). The cause of this alleviation seems a bit counter intuitive, but nonetheless low calorie diets appeared to be an effective treatment for the patients and it is still recommended to lower calories and spread out eating times throughout the day. Sadly, many people developed some pretty bad misconceptions on starving. This continued into today where a lot of diets are starvation diets, which are definitely not recommended by good clinicians. This seems to be a very common occurrence in transferring/translating information though. More recently was gluten being bad for you, but in reality it only hurts those with celiac disease. The first publication about low rations and exercise was made by Elliot Joslin in 1916 validating Apollinaire’s observations (McCoy, 2009).

Things drastically changed though for diabetics in 1921 as mentioned earlier with Banting and colleagues’ discovery of insulin as a form of a treatment (ADA, 2014). In 1936 was the first alternative insulin which functions at a different speed (ADA, 2014). By 1966 the first cure of sorts came about which was a pancreatic transplant (ADA, 2014). 1970 though was one of the first steps towards diabetics getting some direct control over their condition. This was the invention of a glucose meter (ADA, 2014). Insulin pumps were invented in 1976 further developing patient control over their disease (ADA, 2014). What these do is maintain a constant blood glucose for the patient which is in a healthy range limiting hazardous conditions for them. Insulin wasn’t high in supply though making treatment hard to receive until 1982. At this point the FDA approved human insulin production by bacteria for us to use on people (ADA, 2014). Treatments and access to them changed the most in the 1900s comparatively to the previous 3000+ years

            The names associated with diabetes also changed quite a bit along with the treatments that came about. In 1979 the different types were as follows: 1) insulin-dependent 2) noninsulin-dependent 3) Gestational Diabetes and 4) serving as an “other” category (ADA, 2014). This naming didn’t stick though. Instead the names again changed in 1997 to type 1 and type 2 diabetes (ADA, 2014). This was essentially after their different types of treatment instead of the etiology of the disease like previously. With all this though where do we go from here and where is here?

            Well as of 2012 10% of diabetic patients are treatable with insulin (Polonsky, 2012). That means 90% of diabetics largely have a health problem as a result of life style choices such as diet and exercise. What is happening to make this such a large trend? Well, this is a multilayered issue, but many schools are starting to eliminate their physical education programs and recess to increase standardized test scores (Reed, 2013). This is counter to what a lot of research says though about exercise providing large cognitive benefits (Liu-Ambrose & Donaldson, 2012). So not only schools reducing the physical health of their children, but they are also diminishing their mental health. There are also many food deserts in the nation which don’t allow access to healthy varieties of food. There are, of course, ways to remedy these issues and some will likely work better than others. Then there are life style choices; all of these play a factor in diabetes.

            Nutrition is a very large concern to many populations. One thing which can jeopardize nutrition is a food desert. Food deserts are a very large challenge and Ron Finley tackles these head on in his community outreach. What’s being done by him and his volunteers is working in a food desert in LA (TED, 2013). What they are doing in their work is providing fruits and vegetables in public areas where grass had been. The city allows for it as long as maintenance is up kept and many of the community members go out and do this themselves. This has a huge impact on the communities’ nutrition in a very positive way. What else can be done nutritionally? Well, Japan is taking another approach which is education in public school systems (Nerman, 2014). There is a ton of misinformation out there as I stated with things like starvation diets. This would be an amazing way to combat such things and provide children as well as adults with critical thinking skills in regards to what they eat. There are some other policies being proposed as well such as: tax sweetened beverages more, encourage lower calorie diets, and develop stem cell treatment for type 1 diabetics (Polonsky, 2012). The last one can act as a cure without the need for a transplant of an entire pancreas which would be great! We already encourage a low calorie diet a lot of the time, but this doesn’t really deter us from getting an extra-large pizza instead of a medium. Scaring people about potential diseases from making such choices and then informing though is very effective with behavioral change (Aronson, Wilson, & Akert, 2013). So our society could do a better job at encouraging us to stop ruining our pancreas like they do with our lungs via cigarettes. The last one which is increasing taxes on sweetened beverages wouldn’t be very effective. Many people don’t account for tax on an item, but rather their whole bill when grocery shopping. What would make this more effective is if taxes were included in store prices like they are in New Zealand. Things aren’t doom and gloom though and there is still hope for a positive change for the future. As Polonsky puts it “the challenges are still substantial, if we build on past accomplishments, there is every reason for optimism that another breakthrough as dramatic as the discovery of insulin will occur in the foreseeable future, with a similarly dramatic impact” (2012).

Works Cited

Aronson, E., Wilson, T. D., & Akert, R. M. (2013). Social Psychology. London: Pearson.

Association, A. D. (2014, May 9). History of Diabetes. Retrieved from www.diabetes.org: http://www.diabetes.org/research-and-practice/student-resources/history-of-diabetes.html?referrer=https://www.bing.com/

Liu-Ambrose, T., & Donaldson, M. G. (2012). Exercise and cognition in older adults: is there a role for resistance training programmes? Br J Sports Med, 25-27.

McCoy, K. (2009, 11 3). The History of Diabetes. Retrieved from www.everydayhealth.com: http://www.everydayhealth.com/diabetes/understanding/diabetes-mellitus-through-time.aspx

Nerman, D. (2014). Food education the law in Japan. CBC News Health.

Polonsky, K. S. (2012). The Past 200 Years in Diabetes. The New England Journal of Medicine, 1332-1340.

Reed, K. (2013). Physical Education Trend Must Be Reversed. The Huffington Post.

TED (Director). (2013). Ron Finley: A guerilla gardener in South Central LA [Motion Picture].