SNR Diabetes BScN 1 Final 2023 PDF

Diabetes Mellitus (DM) Naghma Rizvi Oct 2022  1 Learning 2 outcomes 3 4 Define types of Diabetes Discuss the etiology, Discuss the etiology,...

Diabetes Mellitus (DM) Naghma Rizvi Oct 2022  1 Learning 2 outcomes 3 4 Define types of Diabetes Discuss the etiology, Discuss the etiology, Discuss the chronic Mellitus pathogenesis and pathogenesis and complications of diabetes manifestations of type I manifestations of type II with focus on: Atherosclerosis Diabetes. Diabetes. Nephropathy Neuropathy & retinopathy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289249/ 2022 Recent Statistics in PAKISTAN GLOBAL TREND Stats of Oct 2020  What is Diabetes It is a metabolic disorder, a disorder of protein, carbohydrate and fat metabolism, resulting from an imbalance between insulin availability and insulin need. Or Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.  Etiological Classification of Diabetes  Type 1 diabetes (T1DM)  Type 2 diabetes (T2DM) (NIDDM)  Other specific types  Gestational diabetes mellitus (GDM)  Mechanism of insulin release from beta cells of pancreas& its action on body cells. Glucose transporter s BET A CEL L Insulin-independent facilitated diffusion of glucose (GLUT 2) in the Heart, kidneys, Intestines, pancreas, and CNS. Glucose is  Insulin works to…. https://www.youtube.com/watch? app=desktop&v=MI3l94BXVlA 01 02 03 04 converts converts converts ensures glucose to glucose to glucose to fats glycolysis in glycogen in glycogen in in adipose rest of the tissue liver cells muscle cell body cells Types of DM https://forms.gle/DmWjcEQEanGiAHfS9 C-PEPTIDE Differentiat es between endogenou s and exogenous Insulin TYPE 1 DM (TIDM) Name the two Immune cells. It is an autoimmune disease in which islets destruction is caused primarily by immune effector cells (B and T cells) reacting against endogenous beta cell antigens  MHC molecules on T cells are trained to recognize self- antigens Type I Diabetes Mellitus (TIDM) Chronic Autoimmune disease (3 components) Environmental triggers & Genetic susceptibility (HLA DR genes) Loss of self-tolerance of T cells Loss of pancreatic β-cells Hyperglycemia Predominantly in childhood Insulin dependent Autoantibodies (3 types) More prone to Ketoacidosis TIDM Restricted entry of Glucose in Type I DM Ninja Nerd https://www.youtube.com/watch?v=-axOMKLkLLQ Autoantibodies and their actions Board  Antibodies produced as a result of Types and role inappropriate immune response Anti Islet cell antibodies (Target Beta of cell self-antigens on plasma autoantibodies membrane) in T1DM Anti-glutamic acid antibodies( Glutamic acid decarboxylase; this enzyme converts glutamic acid into GABA, this in turn stimulates insulin production) Anti-insulin antibodies (target insulin)  Metabolic syndrome Triglyceride > or = to 150 mg /dl Type II Blood Glucose level > or = 100 mg/dl Diabetes HDL < 50 mg in Females Mellitus HDL < 40 mg in males T2DM Blood pressure > or + 135/85mm Hg (presence of 3 or more or the following under metabolic Insulin resistance & Beta cell dysfunction syndrome) Hyperglycemia & hyperinsulinemia Genetic Component (1st degree relative)  Insulin resistance/ decreased insulin sensitivity   Initial decrease in beta cell mass  Increased beta cell apoptosis/decrease regeneration Beta cell  Long standing insulin resistance leading to beta cell exhaustion Dysfunction  Chronic hyperglycemia induce beta cell desensitization – glucotoxocity  Chronic elevation of FF acids cause toxicity to beta cell – lipotoxicity  The failure of insulin to appropriately regulate glucose and fatty acid metabolism, leading to:  Decrease uptake of glucose in muscle Insulin  Reduced glycolysis and glucose oxidation Resistance  Inability to suppress hepatic gluconeogenesis  Increase (Glycogen breakdown)  Increase fatty acid oxidation   High levels of plasma triglycerides  Low levels of HDLs Other  Hypertension metabolic  Systemic inflammation (release of pro- abnormalitie inflammatory cytokines) s in insulin  Abnormal fibrinolysis (PAI-1 inhibit fibrinolysis and role of Nitric oxide) resistance  Macrovascular disease (coronary artery, cerebrovascular and peripheral artery disease) Type II pathophysiology On board  Adverse impact of obesity on Diabetes and insulin sensitivity- 3 Hypothesis Obesity  Non-esterified Free fatty acids  Adipokines  Inflammation  Non-esterified Free fatty acids ICF triglyceride in muscle and liver of obese FA oxidation in liver Cytoplasmic Insulin normally toxic Inhibits intermediates gluconeoge acts on nesis Insulin receptors on liver cells Attenuates insulin signalingon liver cells Enhance gluconeogenesis in liver and muscle cells Hyperglyce mia are Adipokines signalling proteins produced by Adipokines secreted by fat cells. adipose tissue in non- They play a obese individuals major role in Improves Insulin regulating sensitivity insulin metabolism Adipokines decreases and insulin b/c of obesity sensitivity. Some Adipokines decreases adipokines insulin sensitivity enhance Tissue uptake of insulin glucose sensitivity Hyperglyce while others mia affect it  Inflammation Pro-inflammatory cytokines secreted by Adipose tissue to fat deposits Obesity increases pro- inflammatory cytokines Pro-inflammatory cytokines increases insulin resistance Tissue uptake of glucose Hyperglycemia Manifestations of TIDM & T2DM  Signs and Symptoms 3 Polys (TIDM & T2DM)  Diabetic Ketoacidosis Diabetic ketoacidosis   Dehydration  Excessive thirst  Neurological signs (pulling of water from brain cells) Seziure Hemiparesis (weakness of one side Manifestations Babinski reflexes (toe reflex) Aphasia (difficulty in reading, writing and talking) of Muscle fasciculation (uncontrolled twitching) Ketoacidosis Hyperthermia (water inbalance) Hemianopia (Loss of vision in either whole right or left side) Nystagmus(dancing eye) Visual hallucinations The POLYS Polyphagia Polydipsia Polyuria Glycosuria Acute & Chronic Complications of DM  Diabetic Ketoacidosis Three Acute Hyperosmolar Hyperglycemia (HHS) Complications (Only in T2DM) of Diabetes Hypoglycemia (Usually in TIDM) Hyperosmolar Hyperglycemic State  It occurs from a relative excess of insulin in the blood and is characterized by below normal blood glucose levels. It occurs in  People treated with insulin Hypoglycemia injections (Usually in TIDM)  Oral hypoglycemic agents Signs and symptoms have two categories  Altered cerebral functions  Activation of ANS  Hypoglycemia produces behaviors related to altered cellular functions  Headache  Difficulty problem solving Manifestations  Disturbed or altered behavior of  Coma Hypoglycemia  Seizures  anxiety, tachycardia, sweating, vasoconstriction of the skin vessels, cool clammy skin   Neuropathies Nephropathies Long Term complications of Diabetes Retinopathies Gastric Motility https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289249/ 2022 Long term complication of Diabetes Macrovascular complications involve large and medium size muscular arteries in brain, heart and extremities{atherosclerosis}) Microvascular complications involve capillary dysfunction in target organs {Kidney, Eyes, brain} Long term complication of Diabetes (micro and macro) General Patho of chronic complications of DM On board Diabetic Neuropathy & Retinopathy Excess sorbitol in DM In eye it causes In CNS damage Schwan cataracts cells  Neuropathies Thickening of walls of nutrient vessels Segmental (capillaries) to nerves demyelination leading to ischemia. (slowing of impulses) Nephropathy Thickening of the basement membrane of Impaired blood flow leads glomerular capillaries to loss of kidney function leading to impaired and eventually renal blood flow. failure  Retinopathies Neovascularizat Abnormal Scarring and ion and retinal vascular Microaneurysm retinal associated permeability detachment hemorrhage  Infections Inadequate inflammatory response Hyperglycemia Neuropathy and due to vascular vascular disease Sensory deficits insufficiency leading favors growth of to delayed or no microorganism healing. Chronic microvascular complication Neuropathy and vascular insufficiency Neuropathy with or without vascular insufficiency