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group_5_presentation_1_-_type_1_diabetes [2016/01/29 23:30] dmellonr |
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| Decreased insulin production causes an increase in blood glucose levels. For this reason, fat and muscle cells are deprived of glucose for energy. In a healthy person, the insulin is produced by special cells known as beta cells. They allow for these sugars to be moved by other cells. But in a Type 1 diabetic individual, the body’s defense cells attack these beta cells and destroy them (Alberti, G., & Zimmet, 1998). When attacked, the body suffers making it unable for the individual to properly intake glucose, affecting their eating choices. Additionally, without the presence of insulin, the body will allow glucose to build up to unsafe amounts instead of being used for energy intake. It is especially hard for younger children since it is one of the most common illnesses faced (Davendra, Liu, & Eisenbarth, 2004). | Decreased insulin production causes an increase in blood glucose levels. For this reason, fat and muscle cells are deprived of glucose for energy. In a healthy person, the insulin is produced by special cells known as beta cells. They allow for these sugars to be moved by other cells. But in a Type 1 diabetic individual, the body’s defense cells attack these beta cells and destroy them (Alberti, G., & Zimmet, 1998). When attacked, the body suffers making it unable for the individual to properly intake glucose, affecting their eating choices. Additionally, without the presence of insulin, the body will allow glucose to build up to unsafe amounts instead of being used for energy intake. It is especially hard for younger children since it is one of the most common illnesses faced (Davendra, Liu, & Eisenbarth, 2004). | ||
| - | <style-left> | + | {{ :type-1-diabetes-diagram.jpg?500 }} |
| - | {{:type-1-diabetes-diagram.jpg?500|}} | + | |
| + | **Figure 1**: Pathway of insulin in healthy vs. Diabetic individuals | ||
| - | Figure 1: Pathway of insulin in healthy vs. Diabetic individuals | ||
| - | </style> | ||
| ===== Epidemiology ===== | ===== Epidemiology ===== | ||
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| (Daneman, 2006) | (Daneman, 2006) | ||
| - | <style-left> | + | {{ :epi.jpg?300 }} |
| - | {{:epi.jpg?300}} | + | **Figure 2**: Type 1 diabetes incidence rates in children vs. adults |
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| - | Figure 2: Type 1 diabetes incidence rates in children vs. adults | + | |
| - | </style> | + | |
| ===== Signs and Symptoms ===== | ===== Signs and Symptoms ===== | ||
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| - | Figure 3: Clinical and laboratory signs and symptoms of Type 1 Diabetes | + | **Figure 3**: Clinical and laboratory signs and symptoms of Type 1 Diabetes |
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| ===== Diagnosis ===== | ===== Diagnosis ===== | ||
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| The complete diagnosis of T1DM is based on your symptoms and blood tests. Blood tests are a measure of blood sugar levels. Higher blood sugar levels coupled with the aforementioned symptoms is an indication of DM. | The complete diagnosis of T1DM is based on your symptoms and blood tests. Blood tests are a measure of blood sugar levels. Higher blood sugar levels coupled with the aforementioned symptoms is an indication of DM. | ||
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| Type-1 diabetes has been observed to have a direct correlation with the Human Leukocyte Antigen (HLA), the human equivalent of the Major Histocompatibility Complex (MHC). MHC allows for the binding of antigens in order to present select cells to specific antigen receptors located on T lymphocytes (T-cells) (Lie et al., 1999). These major effector cells in the body allow for receptor mediated destruction in the immunological response (Brusko, Wasserfall, Clare-Salzler, Schatz, & Atkinson, 2005). Specific to Type-1 diabetes, irregularities of the HLA gene on chromosome 6 at the IDDM1 locus accounts for approximately fifty-percent of unique genetic content for this pathological disease (Lie et al., 1999). Candidate gene studies conducted display a ninety-percent association rate in regards to two identified haplotype combinations of HLA; DR4-DQ8 and DR3-DQ2 (Lie et al., 1999). A third haplotype, DR15-DQ6 is more prevalent in non-diabetics and thus can be inferred as a protective sequence from autoimmune response towards pancreatic beta-cells (Gillespie, 2006). | Type-1 diabetes has been observed to have a direct correlation with the Human Leukocyte Antigen (HLA), the human equivalent of the Major Histocompatibility Complex (MHC). MHC allows for the binding of antigens in order to present select cells to specific antigen receptors located on T lymphocytes (T-cells) (Lie et al., 1999). These major effector cells in the body allow for receptor mediated destruction in the immunological response (Brusko, Wasserfall, Clare-Salzler, Schatz, & Atkinson, 2005). Specific to Type-1 diabetes, irregularities of the HLA gene on chromosome 6 at the IDDM1 locus accounts for approximately fifty-percent of unique genetic content for this pathological disease (Lie et al., 1999). Candidate gene studies conducted display a ninety-percent association rate in regards to two identified haplotype combinations of HLA; DR4-DQ8 and DR3-DQ2 (Lie et al., 1999). A third haplotype, DR15-DQ6 is more prevalent in non-diabetics and thus can be inferred as a protective sequence from autoimmune response towards pancreatic beta-cells (Gillespie, 2006). | ||
| - | {{:pathophys.jpg|}} | + | {{:screen_shot_2016-01-29_at_11.12.35_pm.png|}} |
| - | Figure 4: Aneurysm development in retinal blood vessels causes fluid leakage to surrounding tissue due to AGEs accumulation in hyperglycaemic individuals. Retrieved from http://www.diabetes.ca/diabetes-and-you/complications/eye-damage-diabetic-retinopathy. | + | **Figure 4**: Location of the INS and HLA gene on chromosome 11 and chromosome 6, respectively. Retrieved from http://ghr.nlm.nih.gov/gene/INS and http://ghr.nlm.nih.gov/gene/HLA-B. |
| An additional genetic factor contributing to Type-1 diabetes can be attributed to sequencing differences of the insulin production gene (INS) located on chromosome 11. Size variations of repeating units in the non-coding region of INS lead to either predisposing or protective attributes of the disease, carrying up to ten percent of genetic content specific to Type-1 diabetic individuals. The number of non-coding repeated units on the INS gene has been classified by a system termed as Variable Number of Tandem Repeats (VNTR) (Nakamura et al., 1987). VNTR can be divided into three categories based on repeating unit length; class 1 containing 26 to 63 repeat units, class 2 containing approximately 80 repeat units, and class 3 containing 141 to 209 repeat units (Vafiadis et al., 2001). Risk percentage has been observed to be inversely proportional to sequencing size, such that class 1 individuals are more highly predisposed to Type-1 diabetes while class 3 individuals exhibit more protective properties against the disease (Vafiadis et al., 2001). After the correlation between VNTR and risk percentage had been identified, influence of VNTR in regards to insulin production had been explored. Speculation has arisen that the effects of VNTR influence insulin production via the transcription of the INS gene as opposed to directly altering the protein sequence itself due to its placement in the non-coding region (Pugliese et al., 1997). | An additional genetic factor contributing to Type-1 diabetes can be attributed to sequencing differences of the insulin production gene (INS) located on chromosome 11. Size variations of repeating units in the non-coding region of INS lead to either predisposing or protective attributes of the disease, carrying up to ten percent of genetic content specific to Type-1 diabetic individuals. The number of non-coding repeated units on the INS gene has been classified by a system termed as Variable Number of Tandem Repeats (VNTR) (Nakamura et al., 1987). VNTR can be divided into three categories based on repeating unit length; class 1 containing 26 to 63 repeat units, class 2 containing approximately 80 repeat units, and class 3 containing 141 to 209 repeat units (Vafiadis et al., 2001). Risk percentage has been observed to be inversely proportional to sequencing size, such that class 1 individuals are more highly predisposed to Type-1 diabetes while class 3 individuals exhibit more protective properties against the disease (Vafiadis et al., 2001). After the correlation between VNTR and risk percentage had been identified, influence of VNTR in regards to insulin production had been explored. Speculation has arisen that the effects of VNTR influence insulin production via the transcription of the INS gene as opposed to directly altering the protein sequence itself due to its placement in the non-coding region (Pugliese et al., 1997). | ||
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| The accumulation of AGEs can cause or accelerate the onset of various diseases in the body including atherosclerosis, retinopathy and nephropathy. The binding of AGEs to Low Density Lipoproteins (LDL) can accelerate atherosclerosis regardless of the level of cholesterol in the serum (Kilpatrick, Alan, & Atkin, 2006). Similarly, the binding of AGEs to blood vessel proteins can compromise the structure of the vessel itself, allowing for the leakage of surrounding plasma and serum proteins. This ultimately leads to the damaging of major organs such as the eye and the kidney, causing diabetic retinopathy and nephropathy respectively (Kilpatrick, Alan, & Atkin, 2006). | The accumulation of AGEs can cause or accelerate the onset of various diseases in the body including atherosclerosis, retinopathy and nephropathy. The binding of AGEs to Low Density Lipoproteins (LDL) can accelerate atherosclerosis regardless of the level of cholesterol in the serum (Kilpatrick, Alan, & Atkin, 2006). Similarly, the binding of AGEs to blood vessel proteins can compromise the structure of the vessel itself, allowing for the leakage of surrounding plasma and serum proteins. This ultimately leads to the damaging of major organs such as the eye and the kidney, causing diabetic retinopathy and nephropathy respectively (Kilpatrick, Alan, & Atkin, 2006). | ||
| - | {{:screen_shot_2016-01-29_at_11.12.35_pm.png|}} | + | {{ :pathophys.jpg?300 }} |
| - | Figure 5: Location of the INS and HLA gene on chromosome 11 and chromosome 6, respectively. Retrieved from http://ghr.nlm.nih.gov/gene/INS and http://ghr.nlm.nih.gov/gene/HLA-B. | + | **Figure 5**: Aneurysm development in retinal blood vessels causes fluid leakage to surrounding tissue due to AGEs accumulation in hyperglycaemic individuals. Retrieved from http://www.diabetes.ca/diabetes-and-you/complications/eye-damage-diabetic-retinopathy. |
| ===== Management of Type 1 Diabetes ===== | ===== Management of Type 1 Diabetes ===== | ||
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| ==== Islet Transplantation ==== | ==== Islet Transplantation ==== | ||
| - | Islet cell transportation is a procedure that is performed to transplant the islets taken from a donated pancreas usually from a deceased donor, into a diabetic patient’s liver (Shapiro, 2006). Inorder to isolate the islets of Langerhans from the deceased donor’s pancreas, a thin tube is introduced into the pancreatic duct which runs throughout the whole pancreas carrying with it a mixture of highly purified enzymes known as collagenases (Shapiro, 2006). The delivery of the collagenase solution into the pancreatic duct leads to the enlargement and distention of the organ, due to the internal pressure (Shapiro, 2006). The swollen pancreas is chopped into small pieces and further transferred into a machine called Ricordi's chamber (Shapiro, 2006). Inside, the Ricordi’s chamber, digestion takes place in order to isolate the islets and prepare for their removal from the solution (Shapiro, 2006). They then go through a process of purification in order to separate the isolated islets from the exocrine tissue and debris. Transplantation starts with placing a small catheter through a tiny incision into the upper abdomen and into the portal vein of the liver (Shapiro, 2006). The patient receives a local anesthetic, and then the islets are infused through the catheter allowing them to enter the diabetic patient’s liver (Shapiro, 2006). Finding the proper placement of the catheter is very risky, and requires the use of an ultrasound and radiography techniques (Shapiro, 2006). After the islets are successfully transplanted in the liver, insulin starts to be produced, resulting in the immediate release of beta cells (Shapiro, 2006). Immunosuppressant drugs are prescribed to patients after the transplant in order to ensure that their immune system doesn’t attach the transplanted islets (Shapiro, 2006). | + | Islet cell transportation is a procedure that is performed to transplant the islets taken from a donated pancreas usually from a deceased donor, into a diabetic patient’s liver (Shapiro, 2006). |
| + | 1) a thin tube is introduced into the pancreatic duct which runs throughout the whole pancreas carrying with it a mixture of highly purified enzymes known as collagenases | ||
| + | 2) This leads to the enlargement and distention of the organ, due to the internal pressure | ||
| + | 3)The swollen pancreas is chopped into small pieces and further transferred into a machine called Ricordi's chamber | ||
| + | 4) Inside, the Ricordi’s chamber, digestion takes place in order to isolate the islets and prepare for their removal from the solution | ||
| + | 5) Purification proceeds in order to separate the isolated islets from the exocrine tissue | ||
| + | 6) Transplantation starts with placing a small catheter through a tiny incision into the upper abdomen and into the portal vein of the liver | ||
| + | 7) The patient receives a local anesthetic, and then the islets are infused through the catheter allowing them to enter the diabetic patient’s liverFinding the proper placement of the catheter is very risky, and requires the use of an ultrasound and radiography techniques | ||
| + | 8) After the islets are successfully transplanted in the liver, insulin starts to be produced, resulting in the immediate release of beta cells Immunosuppressant drugs are prescribed to patients after the transplant in order to ensure that their immune system doesn’t attach the transplanted islets (Shapiro, 2006). | ||
| {{:islet_transplantation_process.jpg|{{:islet_transplantation_process.jpg|}} | {{:islet_transplantation_process.jpg|{{:islet_transplantation_process.jpg|}} | ||
| - | Figure 5: schematic of islet transplantation procedure | + | |
| + | **Figure 6**: Schematic of islet transplantation procedure | ||
| ==== Bi-hormonal Bionic Pancreas ==== | ==== Bi-hormonal Bionic Pancreas ==== | ||
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| The first human study of a Bi-Hormonal Bionic endocrine Pancreas was performed by Russel et al, 2008 in 2008 (Russell et al., 2012). The researchers tested a closed-loop system that took venous plasma glucose (PG) measurements every 5 minutes (Russell et al., 2012). These measurements went into a computer algorithm that was run on a laptop (Russell et al., 2012). Nurses would take the insulin and glucagon doses delivered by the algorithm, and using dual pumps, they would manually enter the doses every 5 minutes over a course of 24 hours (Russell et al., 2012). These insulin pumps delivered the insulin and glucagon through subcutaneous infusion sets (Cleo® 90, Smiths Medical) inserted into the abdomen (Russell et al., 2012). The study only included T1DM subjects with undetectable C-peptides (Russell et al., 2012). Undetectable C-peptides allowed the researchers to ensure that the device is completely controlling their glucose levels, and that the subjects were not making any of their own insulin (Russell et al., 2012). A closed-loop control was performed for 24 hours, including three high carbohydrate meals (Russell et al., 2012). Blood samples were taken every 10 minutes to measure insulin and glucagon levels (Russell et al., 2012). This gave researchers insight in how these drugs were managed in real life (Russell et al., 2012). It was found that glucose control without hypoglycemia is feasible with a bi-hormonal bionic pancreas (Russell et al., 2012). Moreover, the micro dose glucagon was effective and well tolerated (Russell et al., 2012). However, the system still required an accurate continuous glucose monitor (CGM) that was able to make blood glucose measurements every 5 minutes (Russell et al., 2012). | The first human study of a Bi-Hormonal Bionic endocrine Pancreas was performed by Russel et al, 2008 in 2008 (Russell et al., 2012). The researchers tested a closed-loop system that took venous plasma glucose (PG) measurements every 5 minutes (Russell et al., 2012). These measurements went into a computer algorithm that was run on a laptop (Russell et al., 2012). Nurses would take the insulin and glucagon doses delivered by the algorithm, and using dual pumps, they would manually enter the doses every 5 minutes over a course of 24 hours (Russell et al., 2012). These insulin pumps delivered the insulin and glucagon through subcutaneous infusion sets (Cleo® 90, Smiths Medical) inserted into the abdomen (Russell et al., 2012). The study only included T1DM subjects with undetectable C-peptides (Russell et al., 2012). Undetectable C-peptides allowed the researchers to ensure that the device is completely controlling their glucose levels, and that the subjects were not making any of their own insulin (Russell et al., 2012). A closed-loop control was performed for 24 hours, including three high carbohydrate meals (Russell et al., 2012). Blood samples were taken every 10 minutes to measure insulin and glucagon levels (Russell et al., 2012). This gave researchers insight in how these drugs were managed in real life (Russell et al., 2012). It was found that glucose control without hypoglycemia is feasible with a bi-hormonal bionic pancreas (Russell et al., 2012). Moreover, the micro dose glucagon was effective and well tolerated (Russell et al., 2012). However, the system still required an accurate continuous glucose monitor (CGM) that was able to make blood glucose measurements every 5 minutes (Russell et al., 2012). | ||
| - | {{:past.jpg|{{:past.jpg|}} | + | {{:past.jpg?400}} |
| - | Figure 6: the bihormonal bionic endocrine pancreas used in the clinical trial. (Russell, 2012) | + | |
| + | **Figure 7**: The bihormonal bionic endocrine pancreas used in the clinical trial. (Russell, 2012) | ||
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| {{:closed_loop.jpg|}} | {{:closed_loop.jpg|}} | ||
| - | Figure 7: Typical 48-hour closed-loop experiment using a meal priming bolus of 0.035 U/kg. Figure 2A shows the blood glucose values (high carb meals) over the course of 48 hours. Figure 2B shows the insulin levels in blue and glucagon level is in red. (Russell, 2012) | + | **Figure 8**: Typical 48-hour closed-loop experiment using a meal priming bolus of 0.035 U/kg. Figure 2A shows the blood glucose values (high carb meals) over the course of 48 hours. Figure 2B shows the insulin levels in blue and glucagon level is in red. (Russell, 2012) |
| Since, the bionic pancreas was still in its experimental stages, the study used a laptop driven system, instead of a phone driven system. Nowadays, the algorithm is controlled using a smartphone through a custom app. Bluetooth technology allows the pumps and the smartphone to communicate and calculate the required doses of insulin and glucagon needed. This allows the smartphone to control the pumps wirelessly, instructing them to release either insulin or glucagon. | Since, the bionic pancreas was still in its experimental stages, the study used a laptop driven system, instead of a phone driven system. Nowadays, the algorithm is controlled using a smartphone through a custom app. Bluetooth technology allows the pumps and the smartphone to communicate and calculate the required doses of insulin and glucagon needed. This allows the smartphone to control the pumps wirelessly, instructing them to release either insulin or glucagon. | ||
| - | {{:future.jpg|{{:future.jpg|}} | + | {{:future.jpg?400}} |
| - | Figure 8: the bihormonal bionic endocrine pancreas, with the incorporation of a smartphone. (Philip Elmer-DeWitt, 2014) | + | |
| + | **Figure 9**: The bihormonal bionic endocrine pancreas, with the incorporation of a smartphone. (Philip Elmer-DeWitt, 2014) | ||
