Diabetes G5 PDF

UNIVERSITY OF GUYANA COLLEGE OF MEDICAL SCIENCE SCOOL OF MEDICINE DIABETES MED1214: INTEGRATED CASE SEMINAR GROUP 5 DATE:20TH MAY, 2024 FACILITATOR: DR.THOMPSON gROUP mEMBERS Lokesh Sukhraj- 1043428 Trishelle Ross- 1031123 Daryll Trellis- 1045974 Martyn P...

UNIVERSITY OF GUYANA COLLEGE OF MEDICAL SCIENCE SCOOL OF MEDICINE DIABETES MED1214: INTEGRATED CASE SEMINAR GROUP 5 DATE:20TH MAY, 2024 FACILITATOR: DR.THOMPSON gROUP mEMBERS Lokesh Sukhraj- 1043428 Trishelle Ross- 1031123 Daryll Trellis- 1045974 Martyn Pereira- 1048394 Kathleen Hawker-1045798 Table of contents 01-Diabetes Case 02-Physiology Aspects 03-Biochemistry Aspects 04-Human Nutrition Aspects 05-Reference List 01 Case study  Case study A 62-year-old man comes to the physician because of a 2-month history of fatigue and increased urination. The patient reports that he has been drinking more than usual because he is constantly thirsty. He has avoided driving for the past 8 weeks because of intermittent episodes of blurred vision. He had elevated blood pressure at his previous visit but is otherwise healthy. Because of his busy work schedule, his diet consists primarily of fast food. He does not smoke or drink alcohol. He is 178cm, (5ft 10in) tall and weighs 93kg (205lb); BMI is 29kg/m2. His pulse is 75/min and his blood pressure is144/94mmHg. Cardiopulmonary examination shows no abnormalities. Laboratory studies show: Case study hemoglobin A1c 10.1% serum: glucose 243mg/dL creatinine 1.0 MG/DL TOTAL CHOLESTEROL 270 MG/DL HDL CHOLESTEROL 50 MG/DL TRIGLYCERIDES 180 MG/DL  Case study hemoglobin A1c 10.1% uRINE: BLOOD NEGATIVE GLUCOSE 2+ KETONES NEGATIVE ALBUMIN: CREATININE RATION 280 MG/G (N>30) He receives metformin therapy, counselling for lifestyle modifications and ACE inhibitor therapy.  02 Physiology 1. Discuss the underlying cause of the patient’s weariness, excessive urination, and polydipsia. 2. Outline the long-term complications of untreated or poorly controlled diabetes physiology  physiology Chronic complications of DM include: Microvascular complications, including diabetic retinopathy (causing blindness) and diabetic kidney disease (causing proteinuria and nephropathy) Cardiovascular complications resulting from atherosclerosis, including angina, myocardial infarction, heart failure, and stroke Neurologic complications including peripheral neuropathy (numbness, burning, pain) and autonomic nerve disease (orthostatic hypotension) (Pathophysiology of Diabetes Mellitus, 2013)  03 Biochemistry 3. Discuss the molecular basis of insulin resistance and explain how the following metabolic pathways are affected in the diabetic patients (Glycolysis, gluconeogenesis, the Citric Acid Cycle and Beta Oxidation, Cholesterol biosynthesis and Ketone Bodies biosynthesis). 4. Discuss the role of Advanced Glycation End Products in the Complications of Diabetes Mellitus Biochemistry Insulin resistance develops into non-insulin dependent diabetes mellitus (type 2 diabetes also known as maturity onset diabetes mellitus) Insulin resistance is due to tissues responding poorly to insulin and dysfunctional β cells in the pancreas. (Cleveland Clinic, 2021)  Biochemistry Mechanism At the cellular level, insulin normally binds to its receptors. A cascade of event that is important for glucose uptake is initiated. ·The insulin receptor substrate (IRS) protein is phosphorylated. ·Upon insulin binding, it will facilitate the activation of downstream signaling. (Freeman & Pennings, 2023)  Biochemistry Mechanism Activation of phosphoinositide 3 kinase (PI3K) leads to the production of phosphatidylinositol 3,4,5 triphosphate (second messenger) which in turn recruit phosphoinositide 3 kinase. PI3K promotes the translocation of glucose transporter protein such as GLUT 4(Glucose transporter type 4), to the cell membrane, facilitating glucose uptake. Disruption in the translocation process is Glucose transporter type 4. (Freeman & Pennings, 2023)  Biochemistry Mechanism Another disruption factor contributing to insulin resistance is an increase in serine phosphorylation of IRS protein by various kinase such as JNK. Kappa B kinase subunit beta and their degradation inhibits downstream signaling. Elevated level of free fatty acids, activate the protein kinase C Isoform (PCK). (Freeman & Pennings, 2023)  Biochemistry Mechanism ·Protein kinase C isoform activation impairs insulin signaling by phosphorylating IRS proteins and interfering with Phosphoinositide 3-Kinase activation. ·mTORC1 pathway regulates cell growth and metabolism by integrating nutrient and hormonal signals, contributing to insulin resistance. Hyperactivation of mTORC1 in obesity, by inhibiting IRS-1 function and impairing Phosphoinositide 3-Kinase activation, promoting insulin resistance. (Freeman & Pennings, 2023)  Biochemistry Mechanism Dysregulation of MAPK pathway, contributing to insulin resistance, particularly through the extracellular regulated kinase (ERK) pathway. Chronic activation of ERK signaling leads to serine phosphorylation of IRS proteins, inhibiting their function and causing impaired insulin signaling. (Freeman & Pennings, 2023) Summary diagram  Biochemistry How are the various pathways affected in a diabetic patient? Glycolysis Less glucose uptake into cells Reduced glycolytic enzymes activity Disrupt glucose transporters (GLUT) Reduced adenosine triphosphate (ATP) production Gluconeogenesis Cells may feel starve of nutrients Elevate glucagon level Increase blood glucose level (Jin & Ma, 2021)  Biochemistry How are the various pathways affected in a diabetic patient? Citric acid cycle Reduce glucose entry into cells Alter pyruvate conversion Decrease adenosine triphosphate (ATP) production Increase ketones body, which will further lead to a decrease in blood pH Beta oxidation Reduce fatty acid utilization Mitochondrial Dysfunction Ketone body formation (Jin & Ma, 2021)  Biochemistry How are the various pathways affected in a diabetic patient? Cholesterol biosynthesis Disrupts regulation of enzymes in cholesterol biosynthesis, increasing HMG-CoA reductase activity. This leads to the synthesis of cholesterol Dyslipidemia Promote lipid peroxidation and modify lipoproteins. Ketone Bodies biosynthesis Increase fat breakdown Increase lipolysis Formation of ketones body (Jin & Ma, 2021)  (Ferrier, 2017) Biochemistry Significance of AGEs and Diabetic vascular complications Hyperglycemia promotes glycation of cellular proteins leading to the formation of advanced glycation end products (AGEs), in similar fashion to HbA1c formation. AGEs binds to membrane receptors for advanced glycation end-products (RAGEs). The constant activation of the AGE-RAGE system in endothelial cells, initiating the activation of nuclear factor κB which produces accelerated oxidative stress in the cells, and an inflammatory response. Advanced glycation end products (AGEs) that mediate some of the early microvascular changes of diabetes and can reduce wound healing. With inflammation there is decreased secretion of adiponectin (a protein with anti-inflammatory effects) increases FA β oxidation. Consequently, a decrease in this contributes to FFA availability.: In the liver, FFA are converted to TAGs, which are packaged in VLDL and secreted into the bloodstream. VLDLs → LDLs, whose high cholesterol concentration can deposit into the arteries & lead to atherosclerosis. Biochemistry Significance of AGEs and Diabetic vascular complications Reactive oxygen species (ROS) that are formed from the partial reduction of molecular oxygen as byproducts of aerobic metabolism, through reactions with drugs and environmental toxins, or when antioxidant levels diminish, creating the condition of oxidative stress. These highly reactive oxygen intermediates can damage the storage of unsaturated lipids leaving room for the accumulated for saturated lipids. Neutrophils and monocytes have oxygen-dependent mechanisms for killing bacteria, one of which includes the enzymes NADPH oxidase. After internalization of the microorganism has occurred, NADPH oxidase, located in the leukocyte cell membrane, is activated and reduces molecular Oxygen from the surrounding tissue to superoxide, a free radical ROS, as NADPH is oxidized. (Ferrier, 2017)  Biochemistry Significance of AGEs and Diabetic vascular complications NO is the endothelium-derived relaxing factor that causes vasodilation by relaxing vascular smooth muscle, and prevents platelet aggregation. NO is synthesized by eNOS in endothelial cells and diffuses to vascular smooth muscle. Lowering eNOS, causes more intervals of vasoconstriction to occur, increasing the blood pressure, which can damage vessel walls, causing platelet aggregation and atheroma deposition which narrows the vessel diameter, leaving the patient susceptible to thrombosis causing atherosclerosis. (Ferrier, 2017) Biochemistry (Rhee & Kim, 2018)  04 Human Nutrition 5. What is the “diet” for diabetes? 6. EXPLAIN four (4) relevant dietary and lifestyle recommendations to help the patient manage DM. 7. Help the patient plan a day’s meals, taking into consideration the recommended carbohydrate allowances for a day and a meal for DM.  Human Nutrition What is the “diet” for diabetes? There is no such thing as a “diet” for diabetes but eating in moderation is advised.  Human Nutrition EXPLAIN four (4) relevant dietary and lifestyle recommendations to help the patient manage DM. Eat Different Types Of Foods From ALL The Food Groups Daily Reduce His Weight Since He is Overweight. Reduce HIs Intake Of Oily & Fatty Foods/Fast foods that he mainly consumes Get At Least 30 Minutes Daily Physical Activity Human nutrition (Zephirin & Hagley, 1994)  Human nutrition Meal Plan Required carbohydrates per meal - 45 - 75g Snack - 0 - 45g Breakfast - Calcium-rich 2tbps of cornmeal porridge with 2tsp honey added with1 cup low-fat milk and 2 slices toasted whole wheat bread with 2 tsp margarine CARBS = 15g + 8g + 12g + 30g= 65g Midmorning snack 1 cup plain yoghurt with 16 unsalted peanuts Beverage - 1 glass of water CARBS = 8g + 14g = 22g  Human nutrition Meal Plan Lunch - Iron rich 1 cup of chowmein with stir-fried vegetables (1 cup spinach, ½ cup pak choy, ¾ cup bora, ½ cup carrots,½ cup cabbage, ½ cup bell. 3 oz of pot roast chicken breast without skin. Beverage - 1 cup of unsweetened orange juice CARBS = 30g + 24.5g + 20g = 74.5g Mid-day snack - 1 medium apple and 2 tbs of peanut butter Beverage - 1 glass of water CARBS = 25g Dinner 3 oz of fish stewed, 1 cup steamed pumpkin with 1 ½ cups brown rice and ½ cup split peas. Beverage - 1 glass of water. CARBS - 14g + 45g + 15g = 74g 15 grams of carbohydrate (1 serving) raises the blood glucose by approximately 70mg/dl. 05 Reference List  Reference List Cleveland Clinic. (2021, December 16). Insulin Resistance: What It Is, Causes, Symptoms & Treatment. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/22206-insulin-resistance Freeman, A. M., & Pennings, N. (2023). Insulin Resistance. Nih.gov. https://www.ncbi.nlm.nih.gov/books/NBK507839/ Jin, Q., & Ma, R. C. W. (2021). Metabolomics in Diabetes and Diabetic Complications: Insights from Epidemiological Studies. Cells, 10(11), 2832. https://doi.org/10.3390/cells10112832 Pathophysiology of diabetes mellitus. (2013, November 7). Kindred. https://www.kindredhospitals.com/resources/blog-kindred-continuum/2013/11/07/pathophysiology-of- diabetes-mellitus Zephirin, M. & Hagley, K. (1994). Meal Planning for Diabetes. (4th ed) [PDF]. https://iris.paho.org/bitstream/handle/10665.2/4327/MEAL%20PLANNING%20FOR%20DIABETES%20- %201994.pdf;jsessionid=5378642BA761246E5C138EE64B3062FF?sequence=1  Reference List Rhee, S. Y., & Kim, Y. S. (2018). The Role of Advanced Glycation End Products in Diabetic Vascular Complications. Diabetes & Metabolism Journal, 42(3), 188. https://doi.org/10.4093/dmj.2017.0105 Ferrier, D. R. (2017). Lippincott illustrated reviews : biochemistry (7th ed.). Wolters Kluwer, Cop. Caleb,A.(n.d.) , CHRONIC NON-COMMUNICABLE DISEASES -DIABETES MELLITUS Part 2[PDF].Human Nutrition, University of Guyana. thank you!