Diabetes Mellitus Pathophysiology/Epidemiology/Etiology Lecture Notes PDF

Islets of Langerhans Diabetes Mellitus Pathophysiology/ Epidemiology/Etiology January 16, 2025  What is Diabetes Mellitus? Diabetes Mellitus is… -A chronic disease of insulin deficiency or resistance ↳ Absence of insulin Or issues wh insuli...

Islets of Langerhans Diabetes Mellitus Pathophysiology/ Epidemiology/Etiology January 16, 2025  What is Diabetes Mellitus? Diabetes Mellitus is… -A chronic disease of insulin deficiency or resistance ↳ Absence of insulin Or issues wh insulin receptors - Disturbances in carbohydrate, fat and protein metabolism lead to hyperglycemia (elevated blood glucose levels) There are other types of diabetes. For example, diabetes insipidus is characterized by excessive water losses, which results in hyperglycemia due to a hypertonic blood volume (larger solute concentration).  is 3 diabetes > - Type function issues wh Cognitive Let’s Review… Beta cells - insulin secretion hormon scretime (amylin100:1) produc Another - produced at Alpha cells - glucagon Topposit I & insult Delta cells - somatostatin  What does insulin do? 1. Mediates transport of glucose from the blood stream into cells (muscle cells, fat cells) 2. Inhibits glycogenolysis (breaking down glycogen to produce glucose) and gluconeogenesis (breakdown of stored fat and protein to make glucose) 3. Promotes energy storage (glycogen and fat production) and building of body tissues (proteins) – Anabolic hormone Considered  What does glucagon do? 1. Promotes glycogenolysis and gluconeogenesis 2. Inhibits energy storage (glycogen and fat production) and building of body tissues (proteins) Considered catabolic – Sugar Transport by GLUT Transporters GLUT 1 – Glucose uptake in red blood cells and the brain GLUT 2 – Glucose, fructose and galactose uptake in the liver GLUT 3 – Glucose uptake in the brain to in I missed it insuli... dependent GLUT 4 > - the one on – INSULIN-MEDIATED glucose uptake by muscles and adipose tissue (Also some in the brown GLUT 5 – Fructose transporter at the intestinal level  Which GLUT is involved in this glucose transport mechanism? Glat insul ↳ its mediated  * Remember... art import Not all glucose transport is insulin-dependant – Brain, blood cells, & liver use transporters that are NOT insulin-dependant Other hormones influence glucose metabolism  Classifications of Diabetes Mellitus (DM) Pre-diabetes – Impaired fasting glucose (IFG) – Impaired glucose tolerance (IGT) Type 1 DM Type 2 DM Pre-existing DM in pregnancy – Type 1 – Type 2 Gestational diabetes (GDM) (Hypoglycemia)  The Cost of Diabetes - Canada People with diabetes access health services more often – They see doctors and specialists more often – They spend 2-11 times as many days in hospital People with diabetes incur medical costs 2-3 times higher than those without diabetes Canada has been identified as the country with the seventh highest spending on diabetes-related health expenditure, totaling 17 billion US dollars in 2015 (4). With the aging of Canada's population, the total direct health-care costs associated with diabetes are expected to continue to increase (10). https://www.diabetes.ca/health-care-providers/clinical-practice- guidelines/chapter-1#panel-tab_FullText  Impaired Fasting Glucose to Diabetes ↳2 stages by I precuser diabetes developing New intermediate designation Fasting glucose increased (6.1-6.9 mmol/l) – 110-124 mg/dl No clinical signs Individuals may be at higher risk of – Diabetes – CVD  Impaired Glucose Tolerance More established ~ 20 - 25% go on to develop advanced stages of Diabetes Mellitus No clinical signs Hyperglycemia (7.8-11.0 mmol/L) post feeding – 140-198 mg/dl Higher risk of CVD Overview of Type I Diabetes Mellitus About 10-15% of Diabetes Mellitus Starts usually before 20 years of age Absolute deficiency of insulin Peak incidence at 5 years and puberty  Type I Diabetes Mellitus Etiology Strong genetic Genes alone as not enough component Immune system susceptibility e.g. immura Autoimmune disease attachin S system Transmissible agents thecel – The “Hygiene” hypothesis Tomm reces – The “Overload” or “Accelerator” Stressoanother hypothesis durin pregnance Relationship to Type 2 DM! Looking for genes!! Beta cell Failure  Type I Diabetes Mellitus Etiology 85-90% of those with Type 1 DM have circulating antibodies for beta cells, insulin or other beta cell antigens Antibodies attach to insulin and beta cells consequently destroyed – They are  Natural History Natural history – Genetic ‘prodrome’ Environment-genetic interaction The development of autoantibodies peaks around 2 years of life, emphasizing that factors causing the disease occur in early life (even if diabetes manifests in later life) – Once 80-90% of beta cells are lost, minimal insulin is secreted Genetic Predisposition Type 1 Diabetes Asymptomatic period (can last months to years)  Acute Effects Insulin deficiency results in: and then in blood amount of glucos – hyperglycemia, > - High wire – glucosuria (glucose spills into urine), – polyuria (osmotic diuresis due to spillage of glucose into urine), – polydipsia (excessive thirst), – dehydration, – and polyphagia (increased food intake) not entering cells ↳ Gillook  Also Fatigue Weight loss in spite of increased appetite protein and fat are broken down for energy→ body wasting  When lack of glucose is severe Lipid used for fuel – Ketones produced Ketosis of ketones in the blood – Accumulation Ketoacidosis – Uncontrolled ketosis ➔ ↓ blood pH Diabetic ketoacidosis (DKA) – Lowered blood pH  Diabetes Keto-Acidosis Mainly occurs in type 1 diabetics due to complete deficiency of insulin 00 Blood pH decreases Hyperpnea = an exaggerated deep, rapid, or labored respiration. Stupor = a state of near-unconsciousness or insensibility. Can we prevent or treat type 1 diabetes? Overview of Type 2 Diabetes Mellitus 85-90% of DM Disease of aging and obesity developing type 1 Insulin resistance-A stage by – Insulin insufficiency – Relative rather than absolute insulin deficiently Type 2 Diabetes Mellitus Etiology Genetic – Transmitted primarily through an affected parent rather than sibling Obesity – 60-80% DM with BMI > 30 – Insulin resistance common – Metabolic syndrome often seen prior to overt type 2 DM Diet – Fat (saturated fat) complexity of the food matrix – Sugar, glycemic load (GL), glycemic index (GI) Diets of low GI and GL considered particularly important in individuals with insulin resistance/type 2 DM (consensus by the International Carbohydrate Quality Consortium (ICQC)) Morio et al. Nutr Rev. 2016 Jan;74(1):33-47. Augustin et al. Nutr Metab Cardiovasc Dis. 2015 Sep;25(9):795-815. Weijnen et al. Diabet. Med. 19, 41–50 (2002) Natural History of Type 2 Diabetes Mellitus – Genetic predisposition – Large environmental influence oh amounts – Cell receptors resistant to insulin very large bluy inscin not results s Hyper insulinemia bod panding ↓ to it Pancreatic decline with loss of insulin secretion Loss of insulin secretion relative to needs  Natural History of T2D PREDIABETES Impaired Glucose Insulin Tolerance Hyper- Type 2 Resistance Diabetes insulinemia Impaired Fasting Glucose Progression to Type 2 Diabetes over years Kahn et al. (2006) Nature 444, 840–846 Say we have 2 people with normal glucose levels, but one is insulin resistance and one is insulin sensitive Insulin Sensitive Insulin Resistance 20 pmol/L of insulin needed to 100 pmol/L of insulin needed maintain normal glucose levels to maintain normal glucose levels VS Lance Armstrong Homer Simpson  Short-term effects Classic symptoms consistent with DM are possible OR Mild fatigue Mild or no weight loss Mild ketosis; no diabetes keto- acidosis Etiologic Classification of Diabetes Mellitus https://guidelines.diabetes.ca/cpg/chapter3  Hypoglycemia Low blood glucose Two types 1. Fasting/spontaneous - tumors, liver disease, alcoholism, endocrinopathies - Relative or absolute lack of insulin relative to counter- regulatory hormones 2. Reactive/functional - post prandial/absorptive - occurs in DM when 1) too much insulin or 2) too little food - might occur in DM ( typez DM ) prior to diagnosis  Hypoglycemia symptoms Faintness, weakness, tremors, heart palpitations, sweating, hunger, nervousness Headache, confusion, visual disturbances, motor weakness, palsy, ataxia, personality change For DM patients treated with insulin; can progress to insulin shock death and sometimes – Fainting, Comal , – Requires immediate medical attention Hypoglycemia in Diabetes Mellitus Stringent glycemic control Can lead to fear and difficulty attaining glycemic targets Episodes predispose to increased likelihood of more hypoglycemia – called “brittle DM” – Particularly hard to control in type 1 DM Can result in brain damage