TEAM #5 PULSE ASSIGNMENT
Learning Outcomes
What is Type 1 Diabetes Mellitus (T1DM)?
- Be able to describe Type 1 Diabetes Mellitus (T1DM).
- Define autoimmune disease and hyperglycemia.
- Understand how HLA class II molecules contribute to T1DM.
- Understand why T1DM cannot be fully attributed to genetics.
- Be able to identify which age groups are most susceptible to disease onset.
- Understand the pathogenesis of T1DM and identify the consequences of T1DM disease onset.
- Identify the two main diagnostic tests of T1DM and be able to explain how they are used.
- Be able to state the primary and secondary treatments of T1DM.
Stages of Development
Disease Causes
Type 1 VS Type 2
INDEX
Pathogenesis
Diagnostic Factors
Treatment
Knowledge Check
References
WHAT IS TYPE I DIABETES MELLITUS (T1DM)?
T1DM is an autoimmune condition characterized by the T-cell-mediated destruction of pancreatic islet ß-cells, which are responsible for insulin secretion.
STAGES OF DEVELOPMENT
Profound hyperglycemia emerges, often when diagnosis occurs
STAGE 3
STAGE 1
STAGE 2
Onset of hyperglycemia
Destruction of islet ß-cells without evident symptoms or hyperglycemia
DISEASE CAUSES
Type 1 diabetes is thought to have a genetic component to the disease specifically relating to:
2. The insulin gene on chromosome 11
1. HLA class II molecules
Learn More
Learn More
T1DM CANNOT BE FULLY ATTRIBUTED TO GENETICS
Studies have shown that only 30-40% of identical twins both develop the disease, meaning genetic predisposition cannot solely account for T1DM development .
30-40%
Identical twins
Who is affected then?
Type 1 vs. Type 2 DM
T1DM PATHOGENESIS
Type 1 diabetes onset stems from the body's innate immune reaction to a danger signal or viral infection. See below the key steps involved in disease onset.
Click Here
1. Islet β-cell Destruction
2. Glut-4 Downregulation
Glut-4 Dwnregulation
Glucose transporter type 4 (GLUT-4) facilitates glucose entry into insulin-responsive cells at the cell membrane surface. In the absence of the insulin-mediated upregulation of GLUT-4, glucose accumulation will persist in the bloodstream, and result in cellular glucose deprivation
The innate immune response elicits an attack on the pancreatic islet β-cells, leading to diminished insulin production.
DIAGNOSTIC FACTORS
Signs & Symptoms
Test Results
Patient Age
Physicians will consider patient age, with patients under the age of 19 being most likely to present with T1DM
Physicians utilize two main tests:
- Hemoglobin A1C (HbA1c) test
- Random glucose (RPG) test
Physicians will consider the presence of signs and symptoms associated with T1DM
What are the signs and symptoms?
What are the normal levels?
TREATMENT
Exercise
Diet Adjustments
Exogenous Insulin
Having a consistent diet composed of high quaility foods can greatly improve blood sugar levels and reduce the risk of diabetes-related complications.
Exogenous insulin will be administered several times daily, either through injections or by using insulin pumps which mimic physiological insulin secretion.
Exercise is crucial in the management of T1DM because it enhances insulin sensitivity, facilitating better blood glucose control.
Test Your Knowledge
Q2
Q3
Q1
Q4
Q7
Q8
Q6
Q5
References
- Al-Fifi, S. (2010). The relation of age to the severity of Type I diabetes in children. Journal of Family and Community Medicine, 17(2), 87. https://doi.org/10.4103/1319-1683.71990
- Ali, O. (2013). Genetics of type 2 diabetes. World Journal of Diabetes, 4(4), 114. https://doi.org/10.4239/wjd.v4.i4.114
- American Diabetes Association. (2021). 2. classification and diagnosis of diabetes: standards of medical care in diabetes—2022. Diabetes Care, 45(Supplement_1). https://doi.org/10.2337/dc22-s002
- Aulanni’am, A., Wuragil, D. K., Susanto, H., Herawati, A., Nugroho, Y. M., Laili Fajri, W. N., Putri, P. F., Susiati, S., Trijoyo Purnomo, J. D., Taufiq, A., & Soeatmadji, D. W. (2022). The early detection of type 1 diabetes mellitus and latent autoimmune diabetes in adults (LADA) through rapid test reverse-flow immunochromatography for glutamic acid decarboxylase 65 kDa (GAD65). Heliyon, 8(1), e08695. https://doi.org/10.1016/j.heliyon.2021.e08695
- Bähr, I., Bazwinsky-Wutschke, I., Wolgast, S., Hofmann, K., Streck, S., Mühlbauer, E., Wedekind, D., & Peschke, E. (2012). GLUT4 in the Endocrine Pancreas—Indicating an Impact in Pancreatic Islet Cell Physiology? Hormone and Metabolic Research, 44(06), 442–450. https://doi.org/10.1055/s-0032-1306335
- Bowson, J. M. M., Stevens, H., Smyth, D. J., Walker, N. M., Chandler, K. A., Bingley, P. J., & Todd, J. A. (2011). Evidence that HLA class I and II associations with type 1 diabetes, autoantibodies to GAD and autoantibodies to IA-2, are distinct. Diabetes, 60(10), 2635–2644. https://doi.org/10.2337/db11-0131
- Castro, C., & Gourley, M. (2010). Diagnostic testing and interpretation of tests for autoimmunity. Journal of Allergy and Clinical Immunology, 125(2), S238–S247. https://doi.org/10.1016/j.jaci.2009.09.041
- Holt, R. I. G., DeVries, J. H., Hess-Fischl, A., Hirsch, I. B., Kirkman, M. S., Klupa, T., Ludwig, B., Nørgaard, K., Pettus, J., Renard, E., Skyler, J. S., Snoek, F. J., Weinstock, R. S., & Peters, A. L. (2021). The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care, 44(11), 2589–2625. https://doi.org/10.2337/dci21-0043
Type 1 diabetes mellitus
The presentation of pancreatic ß-cell antigens by APCs with specific HLA class II molecules can activate autoreactive T-cells. This ultimately leads to the proliferation of the autoreactive T-cells and the secretion of cytokines which contribute to the destruction of insulin-secreting ß-cells.
HLA Class II Molecules
The human leukocyte antigen (HLA) class II molecules are primarily found on the surface of antigen-presenting cells (APCs). Their main function is to present peptide fragments derived from extracellular proteins to CD4+ helper T-cells, which is crucial for initiating and regulating immune responses. In terms of T1DM, HLA class II molecules present autoantigens to the CD4+ T-cells. This process is believed to trigger an autoimmune response against the ß-cells in the pancreas.
Approximately 10% of all diabetes cases are type 1.
T1DM development occurs predominantly in two distinct age groups: (1) Children aged 5-9 (2) Children aged 10-14
Currently there are 8.4 million cases of T1DM globally.
Learn about Type 2 Diabetes
This correlation is believed to stem from the influence of VNTRs on the expression of the insulin gene within the thymus, which in turn impacts immune tolerance to insulin.
Type 1 diabetes mellitus
Insulin Gene (Chromosome 11)
The insulin gene on chromosome 11 is implicated in T1DM susceptibility through its influence on the immune tolerance to insulin. Variations in the variable number of tandem repeats (VNTR) region directly influences the risk of T1DM. Particularly, individuals possessing shorter repeats are at an elevated risk of developing T1DM, whereas those with longer repeats typically exhibit a lower risk for the disease.
Signs & Symptoms
Hover over the signs/symptoms for definitions or more information.
- Viral infection or a danger signal will stimulate an innate immune response.
- Type I interferon production and immune cell recruitment.
- The initiation of pro-apoptotic pathways and inflammation development.
- Autoantibodies, macrophages, ß-cells, CD8+ and CD4+ T-cells infiltrate at sites of inflammation.
Consequences
What are the conseqences?
1. HbA1c Test
The HbA1c test quantifies the proportion of hemoglobin in the blood that has been glycated by glucose over a four-month period. It serves as a valuable tool in reducing the impact of fluctuations in blood glucose levels that are unrelated to diabetes. A normal HbA1c value is around 5.7%, while a reading above 6.5% suggests the presence of diabetes.
2. RPG Test
The RPG test is taken to measure blood glucose levels, regardless of when food was last eaten, and is a single-point measurement to determine blood glucose levels at that time. Normal levels typically fall below 125 mg/dL (milligrams per deciliter), whereas levels of 200 mg/dL or above indicate diabetes.
Type I Diabetes Mellitus
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Transcript
TEAM #5 PULSE ASSIGNMENT
Learning Outcomes
What is Type 1 Diabetes Mellitus (T1DM)?
Stages of Development
Disease Causes
Type 1 VS Type 2
INDEX
Pathogenesis
Diagnostic Factors
Treatment
Knowledge Check
References
WHAT IS TYPE I DIABETES MELLITUS (T1DM)?
T1DM is an autoimmune condition characterized by the T-cell-mediated destruction of pancreatic islet ß-cells, which are responsible for insulin secretion.
STAGES OF DEVELOPMENT
Profound hyperglycemia emerges, often when diagnosis occurs
STAGE 3
STAGE 1
STAGE 2
Onset of hyperglycemia
Destruction of islet ß-cells without evident symptoms or hyperglycemia
DISEASE CAUSES
Type 1 diabetes is thought to have a genetic component to the disease specifically relating to:
2. The insulin gene on chromosome 11
1. HLA class II molecules
Learn More
Learn More
T1DM CANNOT BE FULLY ATTRIBUTED TO GENETICS
Studies have shown that only 30-40% of identical twins both develop the disease, meaning genetic predisposition cannot solely account for T1DM development .
30-40%
Identical twins
Who is affected then?
Type 1 vs. Type 2 DM
T1DM PATHOGENESIS
Type 1 diabetes onset stems from the body's innate immune reaction to a danger signal or viral infection. See below the key steps involved in disease onset.
Click Here
1. Islet β-cell Destruction
2. Glut-4 Downregulation
Glut-4 Dwnregulation
Glucose transporter type 4 (GLUT-4) facilitates glucose entry into insulin-responsive cells at the cell membrane surface. In the absence of the insulin-mediated upregulation of GLUT-4, glucose accumulation will persist in the bloodstream, and result in cellular glucose deprivation
The innate immune response elicits an attack on the pancreatic islet β-cells, leading to diminished insulin production.
DIAGNOSTIC FACTORS
Signs & Symptoms
Test Results
Patient Age
Physicians will consider patient age, with patients under the age of 19 being most likely to present with T1DM
Physicians utilize two main tests:
Physicians will consider the presence of signs and symptoms associated with T1DM
What are the signs and symptoms?
What are the normal levels?
TREATMENT
Exercise
Diet Adjustments
Exogenous Insulin
Having a consistent diet composed of high quaility foods can greatly improve blood sugar levels and reduce the risk of diabetes-related complications.
Exogenous insulin will be administered several times daily, either through injections or by using insulin pumps which mimic physiological insulin secretion.
Exercise is crucial in the management of T1DM because it enhances insulin sensitivity, facilitating better blood glucose control.
Test Your Knowledge
Q2
Q3
Q1
Q4
Q7
Q8
Q6
Q5
References
Type 1 diabetes mellitus
The presentation of pancreatic ß-cell antigens by APCs with specific HLA class II molecules can activate autoreactive T-cells. This ultimately leads to the proliferation of the autoreactive T-cells and the secretion of cytokines which contribute to the destruction of insulin-secreting ß-cells.
HLA Class II Molecules
The human leukocyte antigen (HLA) class II molecules are primarily found on the surface of antigen-presenting cells (APCs). Their main function is to present peptide fragments derived from extracellular proteins to CD4+ helper T-cells, which is crucial for initiating and regulating immune responses. In terms of T1DM, HLA class II molecules present autoantigens to the CD4+ T-cells. This process is believed to trigger an autoimmune response against the ß-cells in the pancreas.
Approximately 10% of all diabetes cases are type 1.
T1DM development occurs predominantly in two distinct age groups: (1) Children aged 5-9 (2) Children aged 10-14
Currently there are 8.4 million cases of T1DM globally.
Learn about Type 2 Diabetes
This correlation is believed to stem from the influence of VNTRs on the expression of the insulin gene within the thymus, which in turn impacts immune tolerance to insulin.
Type 1 diabetes mellitus
Insulin Gene (Chromosome 11)
The insulin gene on chromosome 11 is implicated in T1DM susceptibility through its influence on the immune tolerance to insulin. Variations in the variable number of tandem repeats (VNTR) region directly influences the risk of T1DM. Particularly, individuals possessing shorter repeats are at an elevated risk of developing T1DM, whereas those with longer repeats typically exhibit a lower risk for the disease.
Signs & Symptoms
Hover over the signs/symptoms for definitions or more information.
Consequences
What are the conseqences?
1. HbA1c Test
The HbA1c test quantifies the proportion of hemoglobin in the blood that has been glycated by glucose over a four-month period. It serves as a valuable tool in reducing the impact of fluctuations in blood glucose levels that are unrelated to diabetes. A normal HbA1c value is around 5.7%, while a reading above 6.5% suggests the presence of diabetes.
2. RPG Test
The RPG test is taken to measure blood glucose levels, regardless of when food was last eaten, and is a single-point measurement to determine blood glucose levels at that time. Normal levels typically fall below 125 mg/dL (milligrams per deciliter), whereas levels of 200 mg/dL or above indicate diabetes.