Physiology of diabetes mellitus and insulin resistance Flashcards
Describe the action of diabetes mellitus
Insulin deficiency =>
- decreased tissue utilisation of glucose
- increased utilisation of AAs and fatty acids
- increased hepatic glycogenolysis
- increased hepatic gluconeogenesis
=> hyperglycaemia
Describe type 1 and 2 diabetes mellitus
Type 1:
- beta-cell destruction => insulin deficiency
- immune-mediated
Type 2:
- insulin has no effect
What causes insulin production to stop?
Pancreatectomy
Pancreatitis
Auto-immunity
Islet cell hypoplasia
Chemical toxicity
What causes insulin to stop working?
Progesterone
Growth hormone
Glucocorticoids
Glucagon
Catecholamines
Thyroid
Obesity
What are the physiological causes of insulin resistance?
Pregnancy
Stress
What are the pathological causes of insulin resistance?
Obesity
Hereditary predisposition
Concurrent diseases
Endocrinopathies e.g., hyperadrenocorticism, acromegaly
Describe the link between insulin resistance and diabetes
Insulin resistance (compensated or uncompensated by insulin)
=> Type 2 diabetes mellitus
Describe the pathogenesis of canine diabetes mellitus
- immune mediated (T cell) destruction of beta cells
- pancreatitis with beta cell destruction
- specific hormones antagonise insulin action e.g., cortisol and growth hormone => peripheral insulin resistnace
Describe the counter regulatory hormones evoked in hypoglycaemia in dogs
Cortisol - hyperadrenocorticism
GH - acromegaly
Catecholamines
Glucagon - glucagonoma
Progesterone
Progesterone => GH production
What are the causes of diabetes mellitus in cats?
Obesity/diet-induced insulin resistance
Islet amyloidosis
Pancreatitis
Insulin-antagonistic drugs (glucocorticoids)
Insulin-antagonistic disease (acromegaly)
Genetics
What are the common types of diabetes mellitus in cats and dogs
Cats - Type 2
Dogs - type 1
What is insulin resistance?
the diminished ability of cells to respond to the action of insulin in transporting glucose from the blood into tissues
Why does obesity lead to insulin resistance?
Inadequate number of insulin receptors
Defective number of insulin receptors
Defective GLUT4 transport proteins
Problems with translocation of GLUT4 to membrane
Interference with function of GLUT4
What is amyloid polypeptide/amylin and how does it cause diabetes mellitus?
Co-secreted with insulin by FELINE beta cells
What are the types of diabetes when classified by therapy requirements
Insulin-dependent diabetes mellitus (IDDM) - Type 1
Non-insulin dependent diabetes mellitus (NIDDM) - Type 2
Describe insulin-dependent diabetes mellitus (IDDM)
Type 1 DM
Most common form of diabetes
~100% in dogs
50-70% in cats
Permanent insulin deficiency
Animal needs exogenous insulin
Describe non-insulin dependent diabetes mellitus (NIDDM)
Type 2 DM
Common in cats - obesity induced insulin resistance
Dogs (rare):
- insulin-antagonism
- drugs - glucocorticoids, progestogens
- conditions - dioestrus
Describe EMS (equine metabolic syndrome)
Insulin resistance
Most common clinical sign = laminitis
High levels of insulin and glucose seen in EMS
What are the most common clinical signs of diabetes mellitus?
PU/PD
Polyphagia
Weight loss
Why does diabetes mellitus cause PU/PD?
Osmotic diuresis:
- Blood glucose exceeds ‘renal threshold’
- Glucose acts as osmotic particle
- Draws water into renal tubule => dilutes urine and increases urine volume
Why does diabetes mellitus cause polyphagia?
Lack of insulin => glucose cannot enter satiety center in hypothalamus (GLUT4 needs insulin to work) => failure to inhibit appetite centre => polyphagia despite hyperglycaemia
Why does diabetes mellitus cause weight loss?
Insulin:glucagon ration falls => ‘starvation’ process
Continuous inter-prandial period/’starvation’ period:
- mobilisation of stores
- catabolic
- amino acids used for gluconeogenesis => increased protein breakdown => muscle wasting
Why does diabetes mellitus cause cataracts?
Glucose uptake into lens => lactate => diffuses out
EXCESS glucose => fructose and sorbitol => do not diffuse => trapped => draw water into lens
Why does diabetes mellitus cause ketoacidosis?
Glucose cannot enter cells as easily
Insulin/glucagon ratio favours catabolism
Shift to fat metabolism for energy => fatty acids => ketones build up => metabolic acidosis => vomiting, diarrhoea, anorexia contribute to dehydration
