L7 - Diabetes

Overview of Diabetes Management

• Focus: Blood glucose regulation and diabetes treatment.

• Reference: Chapter 31 for detailed study material.

Hormonal Regulation of Blood Glucose

• Key Hormones: Control blood glucose levels.

  • Insulin: Lowers blood glucose.

    • Released by pancreas after meals in response to increased blood glucose levels.

    • Facilitates glucose uptake in cells, especially muscle and adipose tissue, by promoting the translocation of GLUT4 transporters to the cell membrane. Glucose is then stored as glycogen in the liver and muscles.

    • Inhibits glucose production in the liver (gluconeogenesis) and promotes fat and protein storage.

  • Glucagon: Raises blood glucose.

    • Released during fasting or hypoglycemia to stimulate glycogen breakdown (glycogenolysis) in the liver, releasing glucose into the bloodstream.

    • Promotes gluconeogenesis from non-carbohydrate sources such as amino acids and glycerol in the liver.

  • Epinephrine (Adrenaline): Mobilizes glucose during stress.

    • Released during stress or exercise; stimulates glycogenolysis in the liver and muscle tissue, providing a quick source of glucose for energy.

    • Inhibits insulin secretion and promotes glucagon secretion, further raising blood glucose levels.

  • Cortisol: Increases glucose levels under prolonged stress.

    • Released during prolonged stress; increases gluconeogenesis in the liver and reduces glucose uptake in peripheral tissues, ensuring the brain has enough glucose.

    • Prolonged exposure to cortisol can lead to insulin resistance.

  • Growth Hormone: Reduces glucose uptake and promotes fat breakdown.

    • Released by the pituitary gland; reduces glucose uptake in muscle and adipose tissue, promoting fat breakdown (lipolysis) and increasing blood glucose levels.

    • Counteracts the effects of insulin.

Insulin Mechanism of Action

• Binding to Receptors:

  • Insulin binds to insulin receptors on target cells (muscle, fat, and liver). These receptors are tyrosine kinases.

  • Binding activates the receptor, triggering a signaling cascade that includes phosphorylation of intracellular proteins, ultimately leading to increased glucose transport into cells via the translocation of GLUT4 transporters to the cell membrane.

• Immediate Effects:

  • Increased glucose uptake in muscle and adipose tissue.

  • Stimulates glycogen synthesis (glycogenesis) in the liver and muscle, converting glucose into glycogen for storage.

  • Inhibits gluconeogenesis in the liver, reducing endogenous glucose production.

• Long-term Actions:

  • Affects gene expression and intermediary metabolism through the Ras-MAP kinase pathway, influencing cell growth and differentiation processes.

• Increased glucose uptake results in: Increased Glycogen synthesis, decresed Glycogenolysis and decreased gluconeogenesis which mantains glucose homeostasis

Glucagon Mechanism of Action

• Secreted by alpha cells in the pancreas during hypoglycemia (low blood glucose levels).

• Effects:

  • Stimulates glycogenolysis (glycogen breakdown) in the liver, releasing glucose into the bloodstream.

  • Promotes gluconeogenesis from non-carbohydrate sources (amino acids, glycerol) in the liver, increasing glucose synthesis.

Other Hormonal Influences

• Somatostatin: secreted by Delta cells and Inhibits insulin/glucagon secretion to fine-tune glucose regulation, preventing extreme fluctuations.

• Diabetes Recognition:

  • Symptoms: Increased appetite (polyphagia), thirst (polydipsia), urination (polyuria), fruity breath (ketosis), fatigue, recurrent infections.

  • Diabetes prevalence in Australia: ~1.2 million people (~4.9% of the population).

Types of Diabetes

• Type 1:

  • Insulin deficiency.

  • Autoimmune destruction of beta cells in the pancreas, leading to little or no insulin production. Requires exogenous insulin for survival.

• Type 2:

  • Initially insulin resistance; may progress to insulin deficiency.

  • Cells become less responsive to insulin, requiring more insulin to achieve the same effect. Over time, the pancreas may not be able to produce enough insulin to overcome this resistance.

  • Most common (95% of diabetes cases).

Medications for Diabetes Management

• Medications Categories: Injectable vs. Oral agents.

• Insulin:

  • Essential for type 1; used in type 2 if oral agents fail.

  • Main unwanted sideeffect is hypoglycaemia

• GLP-1 Agonists: Mimic incretin hormones to enhance insulin release and slow gastric emptying.

  • Benefits include weight loss.

• Oral Medications:

  • Metformin: First-line treatment, improves insulin sensitivity in peripheral tissues and reduces hepatic glucose production; does not stimulate insulin production, thus lower risk of hypoglycemia.

  • Sulfonylureas: Stimulate insulin release from pancreas; risk of hypoglycemia, weight gain due to increased insulin levels.

  • DPP-4 Inhibitors: Enhance incretin hormone action by preventing the breakdown of incretin hormones, leading to increased insulin release and decreased glucagon secretion; low risk of hypoglycemia.

  • Alpha-Glucosidase Inhibitors (e.g., Acarbose): Slow carbohydrate absorption in the intestines; side effects include gastrointestinal symptoms such as flatulence and diarrhea.

  • SGLT2 Inhibitors: Promote glucose excretion via urine by blocking glucose reabsorption in the kidneys; monitor for UTIs and dehydration.

  • Thiazolidinediones (Glitazones): Enhance insulin sensitivity in peripheral tissues by activating PPAR
    eq receptors, which regulate gene expression related to glucose and lipid metabolism; work at a genetic level but may take time for effects.

Specific Oral Medications Mechanisms and Side Effects

• Metformin:

  • Mechanism: Lowers glucose production in the liver, improves insulin sensitivity in peripheral tissues by activating AMPK (AMP-activated protein kinase); side effects: nausea, gastrointestinal upset.

• Sulfonylureas:

  • Mechanism: Increase insulin secretion by binding to SUR1 receptors on pancreatic beta cells, closing KATP channels and depolarizing the cell, leading to calcium influx and insulin release; side effects: hypoglycemia, weight gain.

• DPP-4 Inhibitors:

  • Mechanism: Preventative inhibitors of DPP-4 , therefore degradation of incretins like GLP-1 and GIP; side effects: mild GI discomfort.

• SGLT2 Inhibitors:

  • Mechanism: Block glucose reabsorption in kidneys by inhibiting SGLT2 transporters in the proximal tubule, leading to increased glucose excretion in the urine; side effects: dehydration, UTIs. Can be used in any stage of therapy.

• GLP-1 Agonists:

  • Mechanism: Stimulates insulin secretion and curbs appetite; side effects: nausea, risk of antibody formation.

• Alpha Glucosidase inhibitor - acarbose - inhibits the enzyme alpha-glucosidase, which slows carbohydrate absorption in the intestines; side effects may include gastrointestinal issues such as flatulence, diarrhea, and abdominal pain.

Conclusion

• Diabetes management is multifaceted, involving lifestyle changes, monitoring, and medication.

• Treatment goals include maintaining glycemic control and preventing complications.

• Understanding medication mechanisms and potential side effects is crucial for effective management.

Insulin Injections

• Types of Insulin for Injection:

  • Rapid-acting: Used at mealtime to control postprandial blood glucose levels. Examples: Aspart, Lispro. Onset: 10-15 minutes, Peak: 1-2 hours, Duration: 3-5 hours.

  • Short-acting: Taken 30 minutes before a meal. Example: Regular insulin. Onset: 30 minutes, Peak: 2-3 hours, Duration: 5-8 hours.

  • Intermediate-acting: Covers insulin needs for half a day or overnight. Example: NPH (Neutral Protamine Hagedorn). Onset: 1-2 hours, Peak: 4-12 hours, Duration: 12-18 hours.

  • Long-acting: Steady insulin release over 24 hours, used for basal insulin coverage. Examples: Glargine, Detemir. Onset: 1-2 hours, No Peak, Duration: 24 hours.

• Mechanism of Action:

  • Insulin facilitates the uptake of glucose into cells, particularly in muscle and fat tissue, by binding to insulin receptors and activating intracellular signaling pathways that promote GLUT4 translocation to the cell membrane.

  • It inhibits hepatic glucose production by suppressing gluconeogenesis and glycogenolysis in the liver.

  • Promotes glycogen synthesis in the liver, thus helping to lower blood glucose levels.

• Injection Sites:

  • Common areas include the abdomen, thigh, back of the arm, and buttock.

  • Rotation of injection sites is recommended to prevent lipohypertrophy (scar tissue formation).

• Administration Techniques:

  • Use alcohol wipes to clean the skin before injection.

  • Pinch the skin to lift the subcutaneous tissue and insert the needle at a 90-degree angle for normal weight individuals (45-degree angle for lean individuals) to ensure subcutaneous injection.

  • Inject the insulin slowly to minimize discomfort and ensure proper absorption. Remove the needle without rubbing the area to prevent bruising.

• Storage:

  • Unused insulin should be stored in the refrigerator (36°F to 46°F or 2°C to 8°C); can be kept at room temperature for up to 28 days once opened to avoid loss of potency.

• Additional Considerations:

  • Monitor blood glucose levels regularly to adjust insulin dosages as needed and maintain glycemic control.

  • Be aware of signs of hypoglycemia (low blood sugar) and carry glucose or snacks to treat it promptly. Symptoms include shakiness, sweating, confusion, and dizziness.

• Patient Education:

  • Teach patients about proper technique and how to avoid