Diabetes

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Diabetes mellitus is a metabolic disorder characterised by hyperglycemia due to defects in the production or action of the insulin.

Diabetes mellitus occurs when the patient's Insulin is either absent, not present in high enough quantities for the patient's needs, or not used correctly by the body[1]. Insulin is a hormone that is produced by specialised Beta cells in the islets of Langerhans in the Pancreas. In addition to helping glucose enter the cells, insulin is also important in tightly regulating the level of glucose in the blood. After a meal, an individual's blood glucose level rises. In response to this increase, the Pancreas normally releases more insulin into the bloodstream to help glucose enter the cells of the body and lower blood glucose levels after a meal. When the blood glucose levels are lowered, less insulin is released from the Pancreas. In healthy individuals, this regulatory system helps to keep blood glucose levels in a tightly controlled range. However, in patients with diabetes, insulin secretion is abnormal, resulting in high levels of blood glucose (hyperglycemia) which must be treated.

According to the American Diabetes Association[2]. the different cases of diabetes mellitus can be classified as:

Contents

Type 1 Diabetes[3]

It is also known as insulin-dependent diabetes mellitus. This was also called juvenile diabetes because some people get it early on in their lives, with the most common age of diagnosis is 16-30. It is suggested but not yet scientifically proven that Type 1 diabetes can be caused by an auto-immune response against the pancreatic beta cells preventing the production of insulin, or by a genetic disorder. Many cases of Type 1 diabetes have non-identified etiology so they are considered to be idiopathic. This type of Diabetes is managed by the individual injecting themselves with insulin prior to eating a meal, the amount of insulin injected should be adjusted according to the carbohydrtae (including sugar)  content of that particular meal. There are three different groups of insulin available to patients:

  1. human insulin which is synthetically made to be a match for human insulin
  2. analogue insulin which has a slightly altered molecular order
  3. animal insulin which is not commonly used in modern medicine although some patients claim that this type of insulin makes them more aware of hypos or generally works better for them.

Within these 3 different groups there are six main types of insulin:

  1. Rapid-acting analogues - can be injected before, with or after food as they have a peak action between 0 and 3 hours. These types of insulin only last long enough to work for the meal at which they were taken.
  2. Long-acting analogues - these last for around 24 hours and as such tend to be taken once or twice a day to build up a level of background insulin. They can be taken without food as they do not have a peak action time. For example Tresiba.
  3. Short-acting insulins - these have a peak action of 2 to 6 hours but can last for up to 8 hours. They should be taken around half an hour before eating to deal with the rise in blood glucose that eating the meal will cause.
  4. Medium- and long-acting insulins - like long-acting analogues, these are taken once or twice a day to provide background insulin or can be taken in combination with short-acting insulins/rapid-acting analogues. Their peak activity is between four and 12 hours and can last up to 30 hours.
  5. Mixed insulin – short-acting and medium-acting insulin combined. Which is usually injected about 2 times in the day, one in the morning one in the evening. 
  6. Mixed analogue – rapid-acting analogue and medium-acting insulin combined[4].

Treatment for Type 1 Diabetes

Insulin therapy

Insulin therapy is a treatment where insulin is to be administered in the subcutaneous layer of a diabetic patient's skin using either a syringe, insulin pen or insulin pump. The best insulin regime for a diabetic patient will depend on factors such as the type of diabetes you have, how much your blood sugar fluctuates throughout the day and your lifestyle[5].

Insulin Pumps:

The insulin pump allows insulin to be pumped into the body automatically by the patient controlling the device using Bluetooth. Currently, the most common type is the tethered insulin pump.

Tethered Insulin Pump

The pump is a way to feed insulin into the patient through tubing throughout the day, you are also able to increase the dose to a larger dose at times such as before meal times. The patient would insert a canular under their skin; an adhesive patch is placed over the canular to secure it in place. The insulin would then flow through the tubing of the canular into the body when signalled by the device. The patient can easily control the dose of insulin on the device using the buttons.

Patch Pumps

Patch pumps are very similar to the tethered insulin pumps, however, instead of a canular inserted; the patient would attach the patch pumps directly on the skin with adhesive- instead of using tubing.

Transplant therapy

Medicinal advances in the last few years have allowed for this new but rare form of treatment for patients suffering from type 1 diabetes. This process involves the transplant of either a whole pancreas or just islet cells into the patient in order that they begin to function normally again. This treatment, however, comes with all the drawbacks of generalised transplant treatments including the need for immunosuppressant drugs which can have a profound impact on the individuals life. A lack of donors means this is generally not the favoured method of treatment[6].

Type 2 Diabetes[7]

It is also known as non-insulin dependent diabetes mellitus and is caused due to insulin no longer triggering its' signalling cascade. The Beta cells of the pancreas cease to respond to increased glucose levels in the blood, leading to hyperglycemia. It often develops in adulthood, being highly linked to a poor diet and obesity, particularly in Western cultures. However, Type 2 Diabetes is also prevalent in certain indigenous populations including the Pima Indians in the USA and Aborigines in Australia. There does appear to be a genetic component to the development of the disease, although it has not yet been identified[8].

This type of diabetes is often managed through diet control and exercise but can be supplemented with the use of insulin or medication taken to lower blood glucose levels. One example of a drug which is commonly used is Metformin. This causes AMP kinase activation which in turn down-regulates mammalian target of rapamycin (mTOR) signalling pathway[9]. People with obesity are more likely to be diagnosed with type 2 diabetes as their pancreas is filled with fat, therefore, less insulin can be produced by the beta cells. This is why it is thought that exercise helps manage the disease as burning fat will reduce the strain on the pancreas.

Failure to control blood sugar levels can result in a wide array of complications, from damage to the kidneys and nerves, to cardiovascular disease as a result of gradual damage to the endothelium of vessel walls (through formations of plaques).

Type 3 Diabetes

Type 3 diabetes is another form of diabetes which is being proposed for Alzheimer's disease resulting from a resistance of insulin in the brain. It has been stated that those with type 2 diabetes have a 50%-65% higher risk of developing Alzheimer's disease[10].

Alzheimer's disease is caused due to the formation of extracellular plaques in the brain which contains the amyloid-β protein, and neurofibrillary tangles containing tau proteins. Studies involving mouse models show that increasing blood glucose levels promoted the production of amyloid-β in the brain which can develop into Alzheimer's disease[11].

Other Specific Types of Diabetes[12]

Gestational diabetes mellitus (GDM)[13][14]

It normally occurs during the 3rd trimester of pregnancy.

It occurs when insulin is not enough for the demands of the tissues of a pregnant woman and is a form of hyperglycemia

Gestational diabetes mellitus can be detected by glucose intolerance blood test. Glucose intolerance can sometimes be asymptomatic and in a mild form so it is not very easy to be detected. If GDM is not treated properly 50 % of women usually get Type 2 diabetes later on in life.

Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG)[15]

In patients with IGT there is a loss in insulin sensitivity leading to hyperinsulinism[16]. It is an intermediate state where the glycemia is not high enough to be considered diabetes but is higher than the normal levels.

Diabetes Insipidus

Nephrogenic diabetes insipidus is caused by mutations in aquaporin 2. Usually AQP2 is trafficked to the cell membrane where it facilitates the reabsorption of water into the cell. In the diseased state, the channels are retained inside the cell resulting in the inability to control the concentration of urine being produced[17]. The 2 main symptoms of diabetes insipidus are polydipsia and polyuria. Polysipdipsia is extreme thirst, and polyuria is the production of unusually high volumes of urine. Polyuria is caused by polydipsia[18].

References

  1. http://www.medicinenet.com/diabetes_mellitus/page2.htm
  2. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care January 2009 vol. 32 no. Supplement 1 S62-S67 doi: 10.2337/dc09-S062
  3. Surg Annu. 1978;10:1-21. Replacement of pancreatic beta cells as a treatment for diabetes mellitus: a review. Jonasson O, Hoversten GH.
  4. http://www.diabetes.org.uk/Guide-to-diabetes/Treatments/Insulin/
  5. https://www.mayoclinic.org/diseases-conditions/diabetes/in-depth/insulin/art-20050970
  6. http://www.startstemcells.com/diabetes-type1-treatment.html
  7. Acta Med Indones. 2010 Oct;42(4):204-8. Insulin resistance profile among siblings of type 2 diabetes mellitus (preliminary study). Purnamasari D, Soegondo S, Oemardi M, Gumiwang I. Department of Internal Medicine, Faculty of Medicine, University of Indonesia - dr. Cipto Mangunkusumo Hospital. Jl. Diponegoro no. 71, Jakarta Pusat 10430, Indonesia.
  8. http://medical-dictionary.thefreedictionary.com/diabetes+mellitus
  9. Kisvali K., Elbi G., Sinnett-Smith J., Rozenqurt E. (2009) "Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signalling systems and inhibits pancreatic cancer growth." Cancer Res 69:6539
  10. http://www.diabetes.co.uk/type3-diabetes.html; 23 Jan 2009; Cited 03/12/2016
  11. http://mappingignorance.org/2015/07/08/alzheimers-disease-type-3-diabetes/ - Jaime de Juan-Sanz M.Sc PHD; July 8 2015; Cited: 03/12/2016
  12. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care January 2009 vol. 32 no. Supplement 1 S62-S67 doi: 10.2337/dc09-S062
  13. Diabetes Care. 2010 Oct 26. [Epub ahead of print] Body and Liver Fat Mass Rather Than Muscle Mitochondrial Function Determines Glucose Metabolism in Women with a History of Gestational Diabetes. Prikoszovich T, Winzer C, Schmid AI, Szendroedi J, Chmelik M, Pacini G, Krssák M, Moser E, Funahashi T, Waldhäusl W, Kautzky-Willer A, Roden M. Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
  14. Gestational diabetes mellitus (GDM) is defined as glucose intolerance of various degrees that is first detected during pregnancy. GDM is detected through the screening of pregnant women for clinical risk factors and, among at-risk women, testing for abnormal glucose tolerance that is usually but not invariably, mild and asymptomatic. GDM appears to result from the same broad spectrum of physiological and genetic abnormalities that characterize diabetes outside of pregnancy. Indeed, women with GDM are at high risk for having or developing diabetes when they are not pregnant. Thus, GDM provides a unique opportunity to study the early pathogenesis of diabetes and to develop interventions to prevent the disease.
  15. Clin Chem. 2010 Nov 9. [Epub ahead of print] Prediabetes as a Therapeutic Target. Pour OR, Dagogo-Jack S. Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, Memphis, TN.
  16. Reaven G. M., Greenfield M. S., Diabetes, 30, (Suppl. 2), 66—75 (1981).
  17. The Journal of Cell Biology. (2003). Reversed polarized delivery of aquaporin-2 mutant which causes dominant nephrogenic diabetes insipidus 163(5):1099-109
  18. NHS.(2016).Diabetes. [online] Available at: https://www.nhs.uk/conditions/diabetes/ [Accessed 22nd Oct. 2018].
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