Understanding Treatment Methods for Type 1 Diabetes, Research Paper Example

Type 1 diabetes, or insulin-dependent diabetes, affects many people worldwide. Like most other autoimmune conditions, it is difficult to treat, and there is currently no cure. Though observations and occurrences of type 1 diabetes have been recorded throughout history, it has only been more thoroughly understood in recent years. Current treatment consists of insulin therapy, monitoring blood glucose, and regulating diet and exercise. Further research is needed to promote a better understanding and develop better treatment or find a cure.

Type 1 Diabetes Throughout History

In part, the lack of understanding of type 1 diabetes has postponed proper treatment and a potential cure. Throughout history, there have been many observations and descriptions about the symptoms, such as extreme thirst, frequent urination, and wasting away, as have been described. It is likely that most people developed type 1 diabetes and died very quickly. Since type 1 diabetes usually manifests in younger people, it may have been associated with other diseases of childhood. Diabetes only became recognized as a serious disorder in the 16^th century by Paracelsus.

Though symptoms of type 1 diabetes have been recorded in ancient Egypt and China, the first clinical description was not made until the first century in Greece by Aretaeus of Cappadocia. Many sources, such as Gale (2012) in DIAPEDIA quote Aretaeus’ portrayal of diabetes as “a melting down of the flesh and limbs into urine”. Gale (2012) quotes Aretaeus as reporting diabetes to be slow-developing and chronic; however sickness and death occur quickly. He describes the polydipsia and polyuria associated with diabetes.

Until the 11^th century, diabetes was diagnosed by tasting the urine of suspected diabetics. In the early 19^th century, this method was eliminated after the first chemical tests were able to identify and measure the presence of sugar in the urine. In 1920, the Folin-Wu method enabled blood glucose to be measured via finger-stick sample where it was then taken to a different laboratory. In 1869, Dr. Paul Langerhans discovered the islets of Langerhans cells in the pancreas. These cells are the endocrine portion and contain beta cells, which produce insulin.

Dr. Elliot P. Joslin furthered the knowledge and understanding of diabetes. Throughout his medical career, many close friends and family developed the disease. He advocated the importance of restricting carbohydrates and having regular exercise. In 1916, his textbook The Treatment of Diabetes Mellitus collected case studies to be made available for physicians and students. In 1923, he published the first book geared to educate diabetic patents, the Diabetic Manual—for the Doctor and Patient.

During the latter part of the 19^th century and early 20^th century, connections between diabetes and diet were made.  In the Franco-Prussian War, the French physician Bouchardat noticed that the reduction of sugar in the urine was correlated with the rationing of food. He then developed the idea of individualized diet plans for diabetic patients. The scientist I.V. Pavlov connected the nervous and gastric system acknowledging the importance of digestion.

Insulin was discovered in 1921 and introduced to the public in 1922. Scientists were able to inject either bovine or porcine insulin into diabetic patients. Insulin injections allowed diabetics to live a longer life with fewer episodes of ketoacidosis. However, there were many problems associated with this treatment. The duration of action was short and type 1 diabetics had to continuously take insulin throughout the day. Many diabetics experienced allergic reactions and anaphylaxis due to the high level of impurities in the insulin.

Throughout the twentieth century, improvements in insulin therapy were made. The 1930s produced two significant results. First, insulin with a long-acting duration was introduced. Long-acting insulin benefited diabetics because it caused less hypoglycemic incidences than short-acting insulin. (Cummins, Royle, Snaith, Greene, Robertson, McIntyre & Waugh, 2010) The other advancement was that the distinction between type 1 and type 2 diabetes was established. The clinician Harry Himsworth noted that type 1 diabetics were sensitive to insulin and developed it in their youth, while type 2 diabetics were not sensitive to insulin and did not develop the disease until later in life.

Purified insulin was introduced in the late 1970s and early 1980s. According to Le (2011), prior to 1972, animal insulin products contained 80,000 parts per million, or 8%, impurities. In 1982, the first insulin of human amino-acid sequence was introduced. Eli Lilly’s market brand of insulin used recombinant DNA technology and Novo A/S used a semi-synthetic methodology. Both insulin therapies were available in both short- and long- acting preparations.

Overview of Type 1 Diabetes

Type 1 Diabetes is an autoimmune disorder which occurs when the body can no longer produce insulin. The insulin-producing pancreatic beta cells in the islets of Langerhans are destroyed by the body. Insulin is the hormone which transports glucose into the cells from the blood. If there is no insulin, glucose will accumulate, raising blood sugar. Glucose is the sugar that functions as the main source of energy for the cells that compose muscles and tissues. It is derived from either food or is produced in the liver, where it is stored as glycogen.

The etiology is of type 1 diabetes is unknown, but there are many conjectures as of its cause. Two major risk factors in developing type 1 diabetes are either the result of genetics or exposure to a virus. Other potential risks include living further away from the equator, vitamin D deficiency, early exposure to cow’s milk, or introducing solid foods too early in an infant’s diet. If a child’s mother was under 25 years of age while pregnant or had preeclampsia, his or her risk of developing type 1 diabetes increases. If children are born with jaundice or develop a respiratory infection, they may be more prone to developing type 1 diabetes.

The most common symptoms associated with type 1 diabetes are extreme thirst and a high volume of urination. Other symptoms include extreme hunger with unexplainable weight loss, blurred vision, and fatigue. These symptoms usually develop slowly and may go unnoticed until the disease has progressed to a serious reaction. Early detection occurs usually if there is a family history of diabetes.

There is no cure for diabetes, but with proper treatment, a healthy life is possible. If type 1 diabetes is not properly managed, complications may arise. Diabetes can affect the eyes, causing cataracts, glaucoma, and blindness. Neuropathy, or nerve damage, may cause symptoms such as tingling, numbness, or burning in the extremities. Excessive sugar in the blood can injure the capillaries, damaging the heart and circulatory system. Diabetics have an increased risk of coronary artery disease, heart attack, stroke, atherosclerosis, and hypertension. They may also be predisposed to developing osteoporosis, bacterial and fungal infections, and having complications with pregnancy. Even with proper management of type 1 diabetes, emergency conditions may arise. Hypoglycemia occurs when glucose levels are abnormally low in the blood. Symptoms may include confusion, abnormal behavior, difficulty with vision, sweating, tingling around the mouth, heart palpitations, and may even result in seizures or loss of consciousness.

Hyperglycemia can be very severe and result in a diabetic coma. It can directly harm the eyes, kidneys, nerves and heart. According to the Mayo Clinic in 2012, hyperglycemia does not occur until glucose values are above 200 milligrams per deciliter. Symptoms develop slowly and include high thirst, frequent urination, blurred vision, headache and fatigue. If hyperglycemia is left untreated, diabetic ketoacidosis can result. When insulin is unavailable, the body will breakdown fat, causing acidic ketones to accumulate in the blood and urine. The Mayo Clinic (2012) identifies symptoms of ketoacidosis as sweet-smelling breath, difficulty breathing, nausea, vomiting, abdominal pain, dry mouth, weakness, confusion, and coma.

Diagnosis

Diabetes can be diagnosed from different tests. The glaciated hemoglobin (A1C) test demonstrates blood sugar levels two to three months prior by measuring the percentage of blood sugar attached to hemoglobin. Diabetes is indicated if the A1C is above 6.5%. The A1C informs both the patient and healthcare provider the effectiveness of the patient’s treatment plan and if any alterations should be made. If the A1C test is not able to be administered, diabetes can be diagnosed from a random blood sugar test and a fasting blood sugar test. Diabetes is indicated with levels of 200 mg/dL and 126 mg/dL or higher, respectively.

Insulin Therapy: Benefits and Deficits

Receiving insulin is necessary type 1 diabetics to survive. It may be administered with an injection, pen, or a pump. Insulin therapy, while it helps to prolong life for type 1 diabetics, can be problematic. Treatment methods may be inconvenient and it may produce adverse effects such as weight gain, hypoglycemia, and atherogenesis. (Jones, 2007)

Insulin injections are usually administered once or twice a day, combining both short-and long-acting insulin preparations. Long-acting insulin typically causes less hypoglycemia than short-acting insulin. (Cummins, Royle, Snaith, Greene, Robertson, McIntyre & Waugh, 2010) Neural protamine gagedorn (NPH) is a common form of long-acting insulin which reaches its peak potency three to five hours after injection. If injected at night, there is a significant chance that nocturnal hypoglycemia may occur. Glargine may function as an alternative to NPH. With no peak action time, glargine offers a more consistent level stability reducing the frequency of hypoglycemia.

When insulin is taken more than three times a day, this procedure is referred to as multiple daily injections. The effects are intense and involve long-acting injections in the morning or night, and injections of short-acting insulin before meals. Diabetics must be careful to ensure that they receive the injections at the appropriate times. Because the injections are so frequent, administering multiple daily injections can negate from the quality of life.

When insulin is administered with a pump, it is referred to as continuous subcutaneous insulin infusion (CSII). Pumps mimic pancreatic behavior and continuously provide a base level of insulin, with an increase in amount at meal times. The insulin is delivered according to the time of day, exercise, and food intake. The rate of delivery can be set by the patient. Pumps usually administer insulin through the abdominal wall with a needle. The National Institute for Health and Clinical Excellence (NICE) in 2002 recommended restricted use in type 1 diabetics who were unable to use multiple daily injections due to the high frequency of hypoglycemia. CSII is used less in the United Kingdom (1%) as opposed to other European and North American countries. (Cummins, Royle, Snaith, Greene, Robertson, McIntyre & Waugh, 2010)

CSII has been found to be effective at controlling blood glucose levels, reducing the risk of hypoglycemia. According to a literature review conducted in 2009 by the Ontario Health Technology Assessment Series, CSII pumps caused more hypoglycemic events in type 1 diabetics under the age of 19 who received insulin injections one to two times per day, but less than those receiving multiple daily injections of insulin. The review also found that insulin requirements were lower in CSII pump users than patients receiving multiple daily injections. There was no difference in incidence of ketoacidosis. However, this review reports that the studies were of low-quality.

Along with a reduction in hypoglycemic events, CSII may improve the quality of life because it allows more flexibility in diet, less time spent with injections, and greater participation in social and physical activities. However, even though this is a cost-effective therapy, it is still estimated that it costs £1700 or $2613.58 dollars per year. (Cummins, Royle, Snaith, Greene, Robertson, McIntyre & Waugh, 2010) The high costs may prevent many people from receiving the care that they need. Insurance companies may not provide CSII pumps or they may only be used by families who can afford them.

Additional Treatment Methods for Type 1 Diabetes

Other medications which may be prescribed prophylactically are aspirin and drugs to lower cholesterol and blood pressure. Some diabetics may be prescribed pramlintide, a medication which counters the hypoglycemic effect of insulin. When injected, it balances the blood sugar by mimicking the digestive hormone amylin, slowing the movement of food through the digestive tract and inhibiting glucagon release. (Jones, 2007)

In addition to medication, a healthy diet and exercise program are essential for type 1 diabetics. Diet should be centered on the consumption of whole grains, fresh fruits, and vegetables. Regular exercise will help to control blood sugar levels and maintain a healthy weight. Diabetics should also be astringent in receiving regular checkups and monitoring their blood sugar. Certain factors which may affect blood sugar include stress, work, pregnancy, alcohol and tobacco consumption, increased age, and weight. More permanent solutions for type 1 diabetes are currently being explored. Both pancreatic and islet cell transplants are potential methods of resolving type 1 diabetes. However, both procedures require immune-suppressant drugs, which may prove to be more detrimental to the body than the diabetes. Stem cell transplants may also be a potential solution to resolving diabetes, though more

research needs to be conducted. Stem cells are undifferentiated cells which have the potential to develop into a variety of cell types to perform different functions. Pluripotent stem cells are found in embryos and have the ability to develop into any cell in the body. These stem cells could be used to generate new islet cells to produce insulin to replace those that were destroyed by the immune system, such as the islet cells of pancreas. The cells could be designed to avoid rejection of the immune system, eliminating the need for immune-suppressant drugs. Because they are not as developed, pluripotent stem cells have a higher ability to regenerate. Their “immunomolulatory properties may potentially be used to prevent, arrest, or reverse autoimmunity. Ameliorate innate/alloimmune graft rejection, and prevent recurrence of the disease.” (Chhabra & Brayman, 2013) Using pluripotent stem cells may allow for type 1 diabetics to not only have greater insulin production, but to eliminate all autoimmune responses.

Multipotent stem cells are found in either adults or in umbilical cords. Their functions are more limited than pluripotent stem cells. Multipotent stem cells can only differentiate into cells from the organ system they originated. For example, in order to regenerate a new pancreas, multipotent stem cells would have to originate from a pancreas stem cell. Though these stem cells may be useful for specific treatment, they may not be as beneficial as pluripotent stem cells since they are already developed.

In a 2013 report by the National Institutes of Health, stem cells must be self-renewing and able to differentiate inside the human body. One concern is whether stem cells should produce only beta cells or the simultaneous production of all cells in the islets of Langerhans. If beta cells are isolated, then they may not be as sensitive to changes in glucose concentration as a collection of islet cells and will be able to regulate the amount of insulin released with the concentration of glucose in the blood.

The embryonic stem cells are better able to proliferate when implanted. Most of the research conducted with multipotent stem cells comes from human adult cadavers. However, after cells are differentiated, they are difficult to culture. Though there have been some successes with DNA engineering, once these cells are established, they can no longer produce insulin. Though multipotent cells can be designed to proliferate well and produce insulin, the engineering is complex and type 1 diabetics would still have problems associated with autoimmunity.

Controversy arises from the use of pluripotent stem cells. Stem cell therapy is controversial because of certain religious and ethical beliefs and scientific questions of its safety and effectiveness. Many feel that using cells from an embryo promotes abortion. Religious and political associations question whether this interferes with the embryo’s right to life. Other ethical concerns involve how funding should be spent; should people opposed to the use of pluripotential stem cells be required to pay taxes for federal research? In 2001, former President Bush limited embryonic stem cell research and banned federal funding to only those lines that were already available. This was overturned by President Obama in 2009.

In addition to ethical concerns, there are also concerns for safety. Because embryonic stem cells can develop into so many different cell types, there is concern that they may develop into tumor cells. Tumor cells have been found to develop and spread after they were transplanted into mice. (Arnhold, Klein, Semkova, Addicks & Schraermeyer, 2004) If the stem cells develop into tumor cells, greater problems would arise. In order to better evaluate safety and effectiveness in vivo, more research needs to be done.

Prevalence

Type 1 diabetes used to be referred to as juvenile diabetes, as it commonly manifests in children and adolescents. However, type 1 diabetes can develop at any age and represents approximately estimated 10% of the diabetic population.  According to the Center for Disease Control and Prevention (2011), during 2002-2005, 15,600 youths were diagnosed with type 1 diabetes. In children younger than ten years of age, the number of new cases was 19.7 per 100,000 per year; the number of new cases for children over ten years of age was 18.6 per 100,000. Type 1 diabetes was found to be most prevalent in non-Hispanic white children with the highest rate of new cases at 24.8 per 100,000 per year among those older than ten years.

The Center for Disease Control and Prevention (2011) also reported that diabetes was the seventh leading cause of death in 2007 in the United States based on 71,382 US death certificates. They estimated that it was a contributing cause of death in an additional 160,022 deaths certificates, totaling 231,404. Even though they do not distinguish between type 1 and type 2 diabetes, the Center for Disease Control and Prevention (2011) estimated that not only is diabetes likely to be underreported as the cause of death, but the risk of dying is twice as high for diabetics as those without.

An increase in the incidence of type 1 diabetes has occurred since the middle of the 20^th century (Gale, 2002). Before insulin therapy, Gale notes that type 1 diabetes was not common; but could be due to lack of knowledge, inaccurate diagnosis, or underreporting cases. Gale notes that most of the studies and documentation have occurred in the United States, Scandinavia, and United Kingdom; evidence in other countries and regions has shown an increase in type 1 diabetes as well. He estimates that this increase may be due to exposure to environmental factors, cow’s milk, or the enterovirus. It is also speculated that the occurrence of type 1 diabetes has increased due to higher growth rates and obesity in children, causing the beta cells to work harder.

Though many conjectures have been made on the origin of type 1 diabetes, there is no one single known cause. Because this disease primarily affects children, many organizations have been developed for further research. The SEARCH for Diabetes in Youth is a national study whose mission is to understand diabetes among children and young adults. It is funded by the Centers for Control Disease and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases. .

In a study conducted by SEARCH in 2013, the patterns of insulin regimens with the results of clinical outcomes were examined. Results found that non-Hispanic white children, under age 19, from higher income families whose parents had private health insurance were reported to have either a more intense insulin regimen or no change to their regimen 36 months after the diagnosis. They had a lower baseline A1C and a smaller increase. “Younger age, continuous insulin pump therapy, and change to a [more intensive regimen] were associated with a higher probability of achieving target A1C levels.” (Pihoker, Badaru, Anderson, Morgan, Dolan, Dabelea, Imperatore & Linder, 2013)  The more intensive the insulin therapy, the greater the preservation of the beta islet of Langerhans cells.

There is no simple answer to the cure for type 1 diabetes. Whatever the reason, the increase in cases is a cause for concern. While insulin therapy combined with a sound diet and exercise program help to manage type 1 diabetes, these methods do not offer a complete cure. In order to find a cure for the disease, further research is required. When type 1 diabetes is better understood, an effective resolution may be established.

References

(2011). National diabetes fact sheet, 2011. Retrieved from Center for Disease Control and Prevention website: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf

Achenbach, P., Bonifacio, E., Koczwara, K., & Ziegler, A. (2005). Natural history of type 1 diabtes. Diabetes, 54(2), 525-531. Retrieved from http://diabetes.diabetesjournals.org/content/54/suppl_2/S25.long

Arnhold, S., Klein, H., Semkova, I., Addicks, K., & Schraermeyer, U. (n.d.). Neurally selected embryonic stem cells induce tumor formation after long-term survival following engraftment into the subretinal space. (2004). Investivigative Opthamology & Visual Science, 45(12), 4251-4255. Retrieved from http://www.iovs.org/content/45/12/4251.full

Chhabra, P., & Brayman, K. (n.d.). Stem cell therapy to cure type 1 diabetes: From hype to hope. (2013). STEM CELLS Translational Medicine, Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/23572052

Cummins, E., Royle, P., Snaith, A., Greene, A., Robertson, L., McIntyre, L., & Waugh, N. (n.d.). Clinical effectiveness and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes: Systemic review and economic evaluation. (2010). Health Technology Assessment Programme, 14(11), 1-208. Retrieved from http://www.hta.ac.uk/execsumm/summ1411.htm

Elliot P. Joslin, M.D.. (2013, April 12). Retrieved from http://www.joslin.org/about/elliot_p_joslin_md.html

Gale, A. (n.d.). The rise of childhood type 1 diabetes in the 20th century. (2002). diabetes, 51(12), 3353-3361. Retrieved from http://diabetes.diabetesjournals.org/content/51/12/3353.long

Gale, EAM. Aretaeus of Cappadocia. (2012). DIAPEDIA, Retrieved from http://www.diapedia.org/introduction/aretaeus-of-cappadocia

Health Quality Ontario. Continuous subcutaneous insulin infusion (CSII) pumps for type 1 and adult diabetic populations . (2009). Ontario Health Technology Assessment Series, 9(20), 1-58. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377523/

Jones, M. (n.d.). Therapies for diabetes: Pramlintide and exenatide. (2007). American Family Physician, 75, 1831-1835. Retrieved from http://www.aafp.org/afp/2007/0615/p1831.pdf

Los Angeles Chinese Learning Center. History of diabetes. (n.d.). Retrieved from http://chinese-school.netfirms.com/diabetes-history.html

Le, H. (2011). History of type 1 diabetes treatments. Type 1 Diabetes, (558), Retrieved from http://www.diabetesincontrol.com/articles/features/10756-history-of-type-1-diabetes-treatments

Mayo Clinic Staff. Hyperglycemia in diabetes. (2012, June 14). Retrieved from http://www.mayoclinic.com/health/hyperglycemia/DS01168

Mayo Clinic Staff. Hypoglycemia. (2012, February 22). Retrieved from http://www.mayoclinic.com/health/hypoglycemia/DS00198

National diabetes, statistics, 2011. (2011, December 06). Retrieved from http://diabetes.niddk.nih.gov/dm/pubs/statistics/

Patlak, M. (2002). Combating diabetes. The Journal of the Federation of American Societies for Experimental Biology, 16(14), 1853. Retrieved from http://www.fasebj.org/content/16/14/1853.full

Pihoker, C., Badaru, A., Anderson, A., Morgan, T., Dolan, L., Dabelea, D., Imperatore, G., & Linder, B. (2013). Insulin regiments and clinical outcomes in a type 1 diabetes cohort: the search for diabetes in youth study. Diabetes Care, 36(1), 27-33. Retrieved from http://care.diabetesjournals.org/content/36/1/27.long

Obama ends stem cell research ban. (2009, June 28). CBSNEWS, Retrieved from http://www.cbsnews.com/2100-503767_162-4853385.html

Search for diabetes in youth. (2011, May 20). Retrieved from http://www.cdc.gov/diabetes/projects/diab_children.htm

Type 1 diabetes. (2013, January 23). Retrieved from http://www.mayoclinic.com/health/type-1-diabetes/DS00329

U.S. Department of Health and Human Services, (2009). Human embryonic stem cell policy under former president bush (aug. 9, 2001 – mar. 9, 2009). Retrieved from National Institutes of Health website: http://stemcells.nih.gov/policy/pages/2001policy.aspx

U.S. Department of Health and Human Services, (2013). 7. stem cells and diabetes. Retrieved from National Institutes of Health website: http://stemcells.nih.gov/info/scireport/pages/chapter7.asp