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.

    • Facilitates glucose uptake in cells and stores as glycogen in liver and muscles.

    • Inhibits glucose production and promotes fat/protein storage.

  • Glucagon: Raises blood glucose.

    • Released during fasting to stimulate glycogen breakdown and gluconeogenesis.

  • Epinephrine (Adrenaline): Mobilizes glucose during stress.

  • Cortisol: Increases glucose levels under prolonged stress.

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

Insulin Mechanism of Action

• Binding to Receptors:

  • Insulin binds to insulin receptors on target cells (muscle/fat).

  • Triggers signaling cascade leading to increased glucose transport into cells (via GLUT4).

• Immediate Effects:

  • Increased glucose uptake.

  • Stimulates glycogen synthesis and inhibits gluconeogenesis.

• Long-term Actions:

  • Affects gene expression and intermediary metabolism through the Ras-MAP kinase pathway.

Glucagon Mechanism of Action

• Secreted by alpha cells in the pancreas during hypoglycemia.

• Effects:

  • Stimulates glycogenolysis (glycogen breakdown).

  • Promotes gluconeogenesis from non-carbohydrate sources.

Other Hormonal Influences

• Somatostatin: Inhibits insulin/glucagon secretion to fine-tune glucose regulation.

• 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.

• Type 2:

  • Initially insulin resistance; may progress to insulin deficiency.

  • 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.

• GLP-1 Agonists: Mimic incretin hormones to enhance insulin release.

  • Benefits include weight loss.

• Oral Medications:

  • Metformin: First-line treatment, improves insulin sensitivity, does not stimulate insulin production.

  • Sulfonylureas: Stimulate insulin release from pancreas; risk of hypoglycemia.

  • DPP-4 Inhibitors: Enhance incretin hormone action; low risk of hypoglycemia.

  • Alpha-Glucosidase Inhibitors (e.g., Acarbose): Slow carbohydrate absorption; side effects include gastrointestinal symptoms.

  • SGLT2 Inhibitors: Promote glucose excretion via urine; monitor for UTIs and dehydration.

  • Thiazolidinediones (Glitazones): Enhance insulin sensitivity; work at a genetic level but may take time for effects.

Specific Oral Medications Mechanisms and Side Effects

• Metformin:

  • Mechanism: Lowers glucose production, improves insulin sensitivity; side effects: nausea, gastrointestinal upset.

• Sulfonylureas:

  • Mechanism: Increase insulin secretion; side effects: hypoglycemia, weight gain.

• DPP-4 Inhibitors:

  • Mechanism: Prevent DPP-4 degradation of incretins; side effects: mild GI discomfort.

• SGLT2 Inhibitors:

  • Mechanism: Block glucose reabsorption in kidneys; side effects: dehydration, UTIs.

• GLP-1 Agonists:

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

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.