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.

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