Understand roles of insulin in glucose metabolism
Describe common strategies for reducing blood glucose in hyperglycaemia
Explain mechanisms of action for drugs that lower elevated blood glucose
Compare benefits and risks of these agents, including side effects and hypoglycaemia risk
Definition: Endogenous regulatory substances produced in organs, transported by blood to target cells.
Functions: Stimulate specific cells/tissues into action.
Examples: Insulin, testosterone, oestrogen, cortisol, thyroid hormones.
Pancreatic Function:
Beta cells: Secrete insulin in response to elevated blood glucose.
Alpha cells: Secrete glucagon when blood glucose is low.
Types of Diabetes:
Type 1 Diabetes Mellitus (DM):
Total insulin deficiency; typically autoimmune with familial links.
Early life onset.
Type 2 DM:
Reduced insulin production and insulin resistance; more common with age.
Gestational Diabetes:
Insulin resistance due to increased growth hormones; maternal and fetal hyperglycaemia.
Microvascular Complications:
Retinopathy
Nephropathy
Neuropathy
Macrovascular Complications:
Ischaemic heart disease
Atherosclerosis
Peripheral vascular disease
Stroke
Multi-faceted treatment approaches:
Stimulate insulin production.
Improve cell sensitivity to insulin.
Delay carbohydrate absorption from the gut.
Prolong action of endogenous insulin.
Impair gluconeogenesis.
Replace endogenous insulin.
Key drug classes identified:
Metformin (Biguanide)
Insulin
Sulfonylureas (SU)
DPP-4 Inhibitors
SGLT-2 Blockers.
Anatomy of Pancreas:
Exocrine and endocrine functions.
Endocrine function performed by islets of Langerhans:
Alpha cells: Glucagon
Beta cells: Insulin
Delta cells: Somatostatin
F cells: Pancreatic polypeptide.
Insulin:
Prevents hyperglycaemia.
Counter-Regulatory Hormones:
Counteract hypoglycaemia (insulin's effects):
Glucagon
Adrenaline
Somatostatin
Growth Hormone.
Increases glucose uptake (stimulated by acute blood glucose rise).
Stimulated by incretins (GIP and GLP-1), suppresses blood glucose levels:
Increases glycogen synthesis.
Decreases glycogenolysis & gluconeogenesis.
Released by beta cells in response to:
High blood glucose levels.
Presence of glucagon or protein in the small intestine.
Inhibited by negative feedback:
Hypoglycaemia decreases insulin and glucagon release.
Binds to insulin receptors (type 3 kinase-linked).
Immediate metabolic and longer-term genomic effects (growth, metabolism).
Highest risk of hypoglycaemia.
All forms of insulin require injection.
Potential side effects:
Lipodystrophy
Weight gain
Allergic reactions.
Only available biguanide in Australia.
Common first-line treatment for Type 2 Diabetes.
Mechanisms:
Increases insulin sensitivity.
Suppresses hepatic glucose production.
Low likelihood of causing hypoglycaemia.
Promotes weight loss.
Increases glucose uptake & fatty acid oxidation.
Decreases gluconeogenesis and absorption from the gut.
Prevents post-meal hyperglycaemia.
Does not cause hypoglycaemia or stimulate appetite.
Common: Nausea, vomiting, diarrhea, anorexia, Vitamin B12 absorption reduction.
Rare: Acute hepatitis, rash, lactic acidosis.
Very low hypoglycaemia risk.
Weight-neutral or weight-negative effects.
Reduces hepatic glucose production and increases peripheral uptake.
Classes:
Sulfonylureas
DPP-4 Inhibitors:
Increase insulin secretion; Example: glibenclamide, sitagliptin.
SGLT-2 Inhibitors:
Ex: Dapagliflozin, Dulaglutide.
Mode of Action:
Sulfonylureas stimulate insulin secretion.
DPP-4 Inhibitors increase incretin hormones affecting insulin and glucagon.
SGLT-2 Inhibitors reduce glucose reabsorption.
Hypoglycaemia Risk:
Sulfonylureas: High risk.
DPP-4 Inhibitors: Low risk.
SGLT-2 Inhibitors: Low risk when used alone.
Sulfonylureas: Weight gain, hypoglycaemia risk, cardiovascular issues.
DPP-4 Inhibitors: Headache, muscle pain.
SGLT-2 Inhibitors: UTI, dehydration, nausea, vomiting.
Continuous assessment of available diabetes management options is essential for patient care.