Diabetes Mellitus 1 and 2 PDF

[Diabetes Mellitus 1 and 2] **[Learning Objectives]** - **Understand the pancreas anatomy** and regulation of enzyme secretion. - Explain **hormonal regulation** of blood glucose (insulin, glucagon, etc.). - Differentiate **Type 1, Type 2**, and other types of diabetes. - Discus...

[Diabetes Mellitus 1 and 2] **[Learning Objectives]** - **Understand the pancreas anatomy** and regulation of enzyme secretion. - Explain **hormonal regulation** of blood glucose (insulin, glucagon, etc.). - Differentiate **Type 1, Type 2**, and other types of diabetes. - Discuss the **pathophysiology**, **clinical findings**, and complications of diabetes. **[Pancreas Functions]** - **Digestive Gland**: Secretes alkaline pancreatic juice into the duodenum to aid digestion. - **Endocrine Gland**: Islets of Langerhans contain: - **Alpha (α) cells**: Secrete **glucagon** to raise blood glucose. - **Beta (β) cells**: Secrete **insulin** to lower blood glucose. - **Delta (δ) cells**: Secrete **somatostatin**, inhibiting glucagon and insulin. **[Diabetes Overview]** - **Type 1**: Insulin deficiency due to **autoimmune destruction** of β-cells. - **Type 2**: Insulin resistance or inadequate response, common in adults but rising in children. - **Gestational Diabetes**: Occurs during pregnancy, increases risk of complications but usually resolves after delivery. **[Regulation of Blood Glucose]** - **Insulin**: Lowers glucose by facilitating its uptake, converting it into glycogen, and inhibiting gluconeogenesis. - **Glucagon**: Opposes insulin by stimulating glycogen breakdown and gluconeogenesis. - **Other hormones** (e.g., adrenaline, cortisol, growth hormone) increase blood glucose. **[Insulin Synthesis and Release]** - Pro-insulin is cleaved into **insulin and C-peptide** (C-peptide levels can measure insulin production). - **Glucose \>3.9 mmol/L** stimulates insulin secretion via a series of cellular events, including K+ channel inhibition and Ca2+ influx. - **Incretins** (GLP-1, GIP) released from the gut enhance insulin release. **Slide 15: Control of Insulin Release** - Insulin synthesis is triggered when glucose levels exceed 3.9 mmol/L. - Glucose binds to GLUT2 (a glucose transporter) on β-cells, leading to the phosphorylation of glucose to glucose-6-phosphate. - This process increases the ATP/ADP ratio, causing a rise in ATP, which inhibits ATP-sensitive K+ channels. - Inhibition of K+ channels depolarizes the cell membrane, opening voltage-dependent Ca2+ channels. - The influx of Ca2+ stimulates insulin secretion. - Incretins (GLP-1 and GIP): Hormones from the gastrointestinal tract that enhance insulin release and inhibit glucagon after eating. They act on G-protein receptors on β-cells, boosting insulin production. **Slide 16: Insulin Mechanism of Action** - Insulin binds to its receptor, triggering autophosphorylation of the receptor. - The receptor activates IRS-1 (Insulin Receptor Substrate-1), leading to the activation of enzymes like protein kinase B and MAP kinase. - This cascade causes GLUT4 (a glucose transporter) to move to the cell membrane, enabling glucose uptake into the cell. - Insulin also promotes the uptake of amino acids, potassium, magnesium, and phosphate into cells, while influencing gene expression and enzyme synthesis. **Slide 19: GLUT Types** - GLUT-4: The insulin-dependent glucose transporter for skeletal muscle and adipose tissue. It remains inactive inside the cell and moves to the membrane when insulin triggers it. - GLUT-2: The major transporter of glucose into β-cells and liver cells. It has a low affinity for glucose, meaning it functions when plasma glucose levels are high. - GLUT-1: Found in all tissues and doesn\'t require insulin. It is crucial for glucose transport in nervous system cells. **Slide 22: Gestational Diabetes** - Gestational diabetes occurs in about 6% of pregnancies, with increased risk if the mother is obese, has had significant weight gain, or has a family history of diabetes. - The incidence is decreasing (\~4% per year), likely due to better maternal healthcare. - The condition is thought to be related to hormonal changes during pregnancy that lead to insulin resistance. - Risks associated with gestational diabetes include: - Macrosomia (large baby) or microsomia (small baby) - Neonatal hypoglycemia - Electrolyte disorders - Respiratory distress syndrome - Post-pregnancy: The diabetic effect usually resolves after the child is delivered. **[Pathophysiology]** - **Type 1 DM**: T-cell-mediated destruction of β-cells, influenced by genetic predisposition (e.g., HLA genes) and environmental triggers (e.g., viral infections). - **Type 2 DM**: Involves insulin resistance, often related to **obesity** and metabolic syndrome (e.g., high triglycerides, hypertension). **Slide 30**: 1. Genetic predisposition and environmental triggers (like infections or dietary factors) lead to the formation of auto antigens on insulin-producing β-cells. 2. These auto antigens are processed and presented by antigen-presenting cells. 3. This activates T-helper cells (both Th1 and Th2 lymphocytes). 4. Th1 cells produce cytokines (IFN-γ, IL-2), while Th2 activates B-cells to generate autoantibodies against β-cells. 5. Activated macrophages and cytotoxic T-cells (CD8) attack the β-cells, releasing inflammatory cytokines like IL-1 and TNF-α, causing β-cell destruction. 6. The overall result is the gradual loss of β-cells, leading to insulin deficiency and the onset of Type 1 diabetes. **[Clinical Features]** - **Type 1**: Early onset, rapid symptom progression, insulin-dependent, often lean body type. - **Type 2**: Later onset, slower progression, often linked to obesity, managed with diet, oral agents, or insulin. - Symptoms of **both**: **Polyuria** (frequent urination), **polydipsia** (thirst), and **polyphagia** (hunger). **[Diagnosis]** - **Fasting plasma glucose ≥7.0 mmol/L** or **random plasma glucose ≥11.1 mmol/L** confirms diabetes. - **HbA1c** measures long-term glucose control. **[Diabetic Emergencies]** 1. **Hypoglycemia**: Occurs when blood glucose drops below 3.5 mmol/L. Symptoms include sweating, tremors, confusion, and coma. Treated with fast-absorbing carbohydrates or IV glucose/glucagon. 2. **Diabetic Ketoacidosis (DKA)**: Common in Type 1, marked by hyperglycemia, ketosis, and metabolic acidosis. 3. **Hyperosmolar Non-Ketotic Hyperglycemia (HNKH)**: Seen in Type 2, characterized by severe dehydration and high blood glucose, but without ketones. **[Complications]** - **Microvascular**: Retinopathy, nephropathy, neuropathy. - **Macrovascular**: Increased risk of heart attack, stroke, and peripheral artery disease.