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You will be asked to investigate one aspect of insulin associated disease in humans and animals. The number of students allocated to each topic will be restricted, as indicated on the SCBCH2002 Moodle page. Students who choose their assignment topics early in the semester will therefore have a wider choice.

Choose one of the following topics:

1. The majority of horses presenting with laminitis also display insulin resistance. Explain the link between laminitis and insulin resistance and discuss appropriate treatment/ management strategies.

2. List the signs and symptoms that would be observed in an individual with an insulinoma, explaining why each would be present. How would the individual be treated?

3. Summarise and discuss the scientific evidence supporting the statement that ‘dogs typically develop an autoimmune form of diabetes, similar to T1D.’

4. In Australia, insulin therapy for T1D involves a number of synthetic insulin analogues. Choose one analogue from the list below, describe how its structure differs from natural human insulin and discuss the reasons for, consequences of, that structural change.

Drug name Brand name Manufacturer
a. Insulin Aspart Novorapid Novo Nordisk
b. Insulin Lispro Humalog Eli Lilly
c. Insulin Glulisine Apidra Sanofi-Aventis
d. Insulin determir Levemir Novo Nordisk
e. Insulin glargine Lantus Sanofi-Aventi

5.Would a predatory animal that hunted for its own food be more or less likely to develop diabetes compared to an animal relying on canned pet food? Discuss the dietary changes that could be beneficial in a cat diagnosed with diabetes.

6. Many different drugs are used to treat T2D in Australia; they can be grouped into seven classes as shown below. Choose one class from the list below and explain how the drugs in this class act to aid blood glucose control. Indicate whether drug of this class are effective alone, or whether they are more effective in combination with drugs of another class. a. Biguanides b. Sulphonylureas c. Thiazolidinediones (Glitazones) d. Alpha-glucosidase Inhibitors. e. Dipeptidyl peptidase 4 (DPP4) inhibitors f. Incretin mimetics g. Sodium-glucose transporter (SGLT2) inhibitors

7. Islet cell transplantation is a prospective therapy for diabetes that is currently in the clinical trial phase. Discuss the potential advantages and limitations of this approach.

8. Drugs that inhibit the action of glucagon are being considered as potential therapy for diabetes. Discuss this approach.

Laminitis and Insulin Resistance

Insulinomas are small tumours found in the pancreas that cause it to generate extra amounts of insulin. In most incidences, the tumours are not cancerous and have diameters of not more than two centimetres (Healthline, 2018). The pancreas is an endocrine organ found at the back of the stomach. It has the function of generating hormones such as insulin that regulates the amount of glucose in one’s bloodstream. Generally, the pancreas halts the generation of insulin when the level of glucose of blood drops to low levels. Consequently, this action enables the level of glucose in the blood to return to optimum levels. However, the occurrence of insulinoma in the pancreas disrupts this function by making the pancreas to continue producing insulin even if the level of glucose in the blood is too low. Thus, severe hypoglycaemia (low blood sugar) can develop. Hypoglycaemia is a severe disorder than can result in symptoms such as unconsciousness, light-headedness, and blurred vision. In most dangerous cases, the condition can be life-threatening.

In spite of insulinoma being the most common cell tumour that occurs in the pancreas, the condition is not common. It only occurs in three to four individuals in every one million people. Its exact causes are not known except in very rare familial cases where insulinoma is genetically transmitted from parents to children (Healthline, 2018).

Insulinoma patients do not always portray visible symptoms. However, when the symptoms start, they may vary based on the seriousness of the condition (Qian et al., 2018).

 As a result of the tumours resulting in the generation of excess amounts of insulin, they can lead to symptoms of hypoglycaemia (low blood sugar) such as confusion, weakness, sweating, fast heartbeats and anxiety. The mild symptoms of insulinoma include tremors, hunger, weight gain, mood swings, dizziness, irritability, and blurred or double vision.

Normally, the high levels of insulin lead to hypoglycaemia (low blood sugar levels) which in turn results in symptoms such as hunger and anxiety. Consequently, the patients tend to eat more regularly to avoid hunger leading to weight gain, which is another noticeable manifestation of the condition (Kerkar, 2018).

More serious symptoms of the condition may interfere with the brain. Also, they may interfere with the adrenal glands hence affecting regulation of the heart rate and stress response leading to a fast heart rate (more than ninety five beats per minute) (Service and Vella, 2018). At times, insulinoma can result in symptoms that are same as those displayed by epilepsy (a neurological condition characterized by seizures or convulsions). More severe cases of insulinoma can result in symptoms such as coma or loss of consciousness, concentration difficulties, seizures or convulsions, and rapid heart rate. In some incidences, the tumours can expand and be distributed to different parts of the body. In such situations, the patients can exhibit symptoms such as diarrhoea, jaundice (the skin and eyes become yellowish), back pain and abdominal pain (Service and Vella, 2018).

Signs and Symptoms of Insulinoma

The loss of consciousness and development of seizures normally result when the amount of sugar in blood suddenly drops to very low levels. The most notifiable neurological characteristic presented by insulinoma is confusion and as the condition progresses, symptoms such as convulsion, motor deficits, and coma start to occur. Low blood sugar levels often affect the cerebral neurons in the absence of internal anomalies in the cerebral circulation leading to an overall dysfunction characterized by diffuse low activity in electroencephalography (EEG) (Faigle, Sutter, and Kaplan, 2013). In this case, the clinician has to prescribe anti-epileptics for the patient. Thus, this episodic character of low blood sugar level in insulinoma also makes the symptoms to vary and hence the diagnosis delays.

Normally, the doctor performs a blood test to monitor the levels of insulin and blood sugar in the bloodstream. High insulin levels with low levels of sugar in the blood indicate the manifestation of insulinoma. Also, the test checks for other hormones that influence the production of insulin, medications that compel the pancreas to generate more insulin, and the proteins that inhibit insulin production.

If the doctor confirms that the patient has insulinoma after the blood test, he or she may instruct a seventy-two-hour fast (Shreenivas, and Leung, 2014). The patient will have to stay in the hospital while fasting to enable the doctor to monitor the level of sugar in the bloodstream. The doctor measures the patient’s blood sugar levels at intervals of at least six hours. The patient will not be allowed to drink or eat anything apart from water throughout the fasting period. In case the patient has insulinoma, he or she will probably have low levels of blood sugar within the first forty eight hours of fasting.

The doctor then performs more tests to affirm the diagnosis. Such imaging tests include the CT-Scan and magnetic resonance imaging (MRI). Such tests enable the doctor to identify the size and location of the insulinoma tumours (Ali, 2018). In cases where the tumours cannot be identified using the MRI or CT-Scan, the doctor can use the endoscopic ultra-sound. During this process, a long and flexible tube is inserted into the patient’s mouth and directed down via the stomach and the small intestines. The tube has ultra-sound probes which emit sound waves that generate comprehensive images of the patient’s pancreas. After the identification and location of the tumour, the doctor extracts a small sample of the tissues for examination purposes. The samples are then used to establish if the tumour is cancerous.

Dogs and Autoimmune Diabetes

Surgery

Surgical extraction of the tumour is always the best option for treating insulinoma. Also, small parts of the pancreas can be extracted in cases of several tumours (Okabayashi, 2013). Typically, surgery cures insulinoma. There are different types of surgery that can be used to treat insulinoma. Normally, the number of tumours and their location determine the type to be performed. The required type of surgery depends on factors such as tumour size, the location of the tumour in the pancreas and whether the patient has one or several tumours. Also, the doctor may suggest that the patient undergoes surgery even if the malignant insulinoma cannot be extracted completely. Thus, removing as much of insulinoma as possible may help to counteract symptoms by reducing the amount of insulin generated. The types of surgeries to be performed are explained below

This type of surgery involves the removal of tumours that are less than two centimetres in diameter (Crippa, 2018).

Normally, this type of surgery is selected if the patient only has one tumour in the pancreas. It is a minimally invasive process with low risks which involves the making of small incisions in the patient’s abdomen and insertion of a laparoscope via the incisions. A laparoscope is a thin and long tube that has a light of high intensity and high resolution cameras at the tip (Aggeli et al., 2016). The camera captures and displays images on a screen, enabling the doctor to view the internal parts of the patient’s abdomen while directing the instrument. After identifying the insulinoma, the surgeon removes it. Multiple insulinomas require the removal of some parts of the pancreas. At times, the surgeon may also be required to remove some parts of the stomach or liver (Aggeli et al., 2016).

This type of surgery is preferred when the tumour found at the head of the pancreas has a diameter of more than two centimetres or if the patient has multiple tumours. Also, the patient will require an ultra-sound scan during the surgery procedure to check for more tumours. Some of the patients may need the removal of parts of or the entire pancreas. Besides, neighbouring organs may be removed as well. Thus, the first surgical procedure of the open surgery is total pancreatectomy which involves the removal of the entire pancreas (Wei, Xuesong, and Jianping, 2016). The second one is referred to as pylorus preserving pancreaticoduodenectomy (PPPD) and it involves the removal of the pancreatic head while the third operation is PPPD with part of the stomach being removed as well (Wei, Xuesong, and Jianping, 2016). Lastly, distal pancreatectomy may be used to remove the tail of the pancreas.

Synthetic Insulin Analogues Used in Australia

The open surgery operations are major procedures used in the treatment of insulinoma and may be accompanied with risks. Normally, the surgeon talks the patients through the benefits and risks of the open surgery. The main aim of this type of surgery is to try and cure insulinoma and hence the patient may consider the process to be worth the risks.

In the case of Von Hippel-Landau or MEN 1 syndrome, the patient may probably develop more tumours after removal of the first one (Mohd, 2017). These are called rare family syndromes. In such cases, the surgeon may suggest that the removal of more part of the pancreas. Also, an abdominal operation may be necessary

In some cases, surgical removal of the tumour may not cure insulinoma. This incidence is common when the insulinoma is cancerous. The treatment options for cancerous insulinoma are described below.

Surgery

The doctor may suggest that the patient undergoes surgery even if the malignant insulinoma cannot be extracted completely. Thus, removing as much of insulinoma as possible may help to counteract symptoms by reducing the amount of insulin generated. For cancerous insulinomas that may have expanded to the liver might require surgical extraction of the tumours. This operation is major and always has risks. Therefore, the patient may be required to think critically about the merits. Normally, the doctor will inform the patient about the benefits and risks and provide answers to any questions if available.

This technique utilizes the heat generated by radio waves to destroy the cancerous cells. This method can be used instead of the open surgery to counteract the symptoms of insulinoma.

This method utilized the cold probe to kill the tissues and cells by freezing. Also, the method can be used instead of open surgery.

The patient may require direct chemotherapy into the location of the tumour in the liver. Also, the patient might need an injection of a substance which inhibits the supply of blood to the tumour. Such substances may encompass tiny plastic beads or gel that helps to maintain the chemotherapy with the tumour location (Bester et al., 2014).

This process involves the injection of microscopic beads covered with radioactive substances referred to as Yttrium-90 into the bloodstream that is headed to the liver. Thus, this is a form of directed radiotherapy (Ferrer-Garcia, 2013).

This procedure may be used to control insulinoma symptoms that cannot be treated by surgery. The process uses drugs such as streptozocin and doxyrubicin (Miranda, 2018).

Causes and Symptoms of Hypoglycaemia

It may be very hard to endure the symptoms of insulinoma. A diet full of glucose is highly recommended as it may help to boost the blood sugar level of the patient. Also, identifying the symptoms of hypoglycaemia helps the patient to quickly correct the condition by adhering to a diet that contains a lot of glucose. Drugs such as diazoxide may help to control blood sugar level by minimizing the production of insulin. It is often taken as a tablet. However, the drug has some side-effects which include loss of appetite, the build-up of fluid in parts of the body such as the legs and the sickness feeling. There are other drugs that can be used to regulate blood sugar level. They include steroids, verapamil, and diphenylhydantoin. Other tumours contain somatostatin receptors hence requiring the use of somatostatin analogue medication such as lanreotide and octreotide to minimize the level of insulin generated in one’s body (Matej, Bujwid, and Wro?ski, 2016)

Conclusion

It is very important to monitor the insulinoma patients after removal of the first tumour. Normally, most of the patients recover fully without any challenges after surgery. Nevertheless, insulinomas can return afterwards especially in those patients with more than one tumour.

Also, some people may develop diabetes after removal of the first tumours. Such incidences commonly occur when a bigger part of the pancreas or the entire pancreas is removed. Besides, most complications may occur in patients who had cancerous tumours. Ideally, these cases are specifically true when the tumours are transmitted to other body organs and thus the surgeon may be unable to completely remove all the tumours. In such cases, more follow up and treatment will be required. Fortunately, there are very rare cases of cancerous insulinomas.

This piece of writing has described the signs and symptoms manifested in insulinoma patients, further explanation of their presence, the surgical treatment of non-cancerous insulinomas as well as the treatment options for cancerous insulinomas. The paper has also concluded with a recommendation of the long-term outlook of the condition.

References

Aggeli, C., Nixon, A., Karoumpalis, I., Kaltsas, G. and Zografos, G. 2016. Laparoscopic surgery for pancreatic insulinomas: an update. HORMONES, 15(2), pp.157-169.

Ali, Z., 2018. Insulinoma: Practice Essentials, Background, Pathophysiology. [online] Emedicine.medscape.com. Available at: https://emedicine.medscape.com/article/283039-overview [Accessed 5 Oct. 2018].

Bester, L., Meteling, B., Boshell, D., Chua, T.C. and Morris, D.L., 2014. Transarterial chemoembolisation and radioembolisation for the treatment of primary liver cancer and secondary liver cancer: a review of the literature. Journal of medical imaging and radiation oncology, 58(3), pp.341-352.

Crippa, S., 2018. Surgical Management of Insulinomas. Archives of Surgery, 147(3), p.261.

Faigle, R., Sutter, R. and Kaplan, P.W., 2013. The electroencephalography of encephalopathy in patients with endocrine and metabolic disorders. Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society, 30(5).

Ferrer-Garcia, J.C., Gonzalez-Cruz, V.I., Navas-DeSolis, S., Civera-Andres, M., Morillas-Arino, C., Merchante-Alfaro, A., Caballero-Díaz, C., Sánchez-Juan, C. and Herrero, C.C., 2013. Management of malignant insulinoma. Clinical and Translational Oncology, 15(9), pp.725-731.

Healthline. 2018. Insulinoma: Causes, Symptoms, and Diagnosis. [online] Available at: https://www.healthline.com/health/insulinoma [Accessed 5 Oct. 2018].

Kerkar, P., 2018. Insulinoma|Causes|Symptoms|Treatment|Diagnosis. [online] ePainAssist. Available at: https://www.epainassist.com/abdominal-pain/pancreas/insulinoma [Accessed 5 Oct. 2018].

Matej, A., Bujwid, H. and Wro?ski, J., 2016. Glycemic control in patients with insulinoma. Hormones (Athens), 15(4), pp.489-99.

Miranda, G., 2018. Malignant insulinoma chemotherapy resistant, pancreatic neuroendocrine tumor of uncertain prognosis. Journal of Clinical and Translational Endocrinology: Case Reports, 8, pp.16-18.

Mohd, A., 2017. Insulinoma in MEN type 1 mistaken as temporal lobe epilepsy. Endocrine Abstracts.

Okabayashi, T., 2013. Diagnosis and management of insulinoma. World Journal of Gastroenterology, 19(6), p.829.

Qian, S.Y., Hare, M.J., Pham, A. and Topliss, D.J., 2018. Insulinoma presenting with post-prandial hypoglycaemia following fundoplication. Endocrinology, diabetes & metabolism case reports, 2018.

Service, J. and Vella, A., 2018. Insulinoma. [online] Uptodate.com. Available at: https://www.uptodate.com/contents/insulinoma [Accessed 5 Oct. 2018].

Shreenivas, A.V. and Leung, V., 2014. A rare case of insulinoma presenting with postprandial hypoglycemia. The American journal of case reports, 15, p.488.

Wei, C., Xuesong, X. and Jianping, G., 2016. Diagnosis and Surgical Treatment of Insulinoma in Sixteen Cases. American Journal of Cancer, 4(1), pp.8-12.

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