Physiology of diabetes mellitus and insulin resistance

Question 1

Describe the action of diabetes mellitus

Answer 1

Insulin deficiency =>
- decreased tissue utilisation of glucose
- increased utilisation of AAs and fatty acids
- increased hepatic glycogenolysis
- increased hepatic gluconeogenesis
=> hyperglycaemia

Question 2

Describe type 1 and 2 diabetes mellitus

Answer 2

Type 1:
- beta-cell destruction => insulin deficiency
- immune-mediated

Type 2:
- insulin has no effect

Question 3

What causes insulin production to stop?

Answer 3

Pancreatectomy
Pancreatitis
Auto-immunity
Islet cell hypoplasia
Chemical toxicity

Question 4

What causes insulin to stop working?

Answer 4

Progesterone
Growth hormone
Glucocorticoids
Glucagon
Catecholamines
Thyroid
Obesity

Question 5

What are the physiological causes of insulin resistance?

Answer 5

Pregnancy
Stress

Question 6

What are the pathological causes of insulin resistance?

Answer 6

Obesity
Hereditary predisposition
Concurrent diseases
Endocrinopathies e.g., hyperadrenocorticism, acromegaly

Question 7

Describe the link between insulin resistance and diabetes

Answer 7

Insulin resistance (compensated or uncompensated by insulin)
=> Type 2 diabetes mellitus

Question 8

Describe the pathogenesis of canine diabetes mellitus

Answer 8

1. immune mediated (T cell) destruction of beta cells
2. pancreatitis with beta cell destruction
3. specific hormones antagonise insulin action e.g., cortisol and growth hormone => peripheral insulin resistnace

Question 9

Describe the counter regulatory hormones evoked in hypoglycaemia in dogs

Answer 9

Cortisol - hyperadrenocorticism
GH - acromegaly
Catecholamines
Glucagon - glucagonoma
Progesterone
Progesterone => GH production

Question 10

What are the causes of diabetes mellitus in cats?

Answer 10

Obesity/diet-induced insulin resistance
Islet amyloidosis
Pancreatitis
Insulin-antagonistic drugs (glucocorticoids)
Insulin-antagonistic disease (acromegaly)
Genetics

Question 11

What are the common types of diabetes mellitus in cats and dogs

Answer 11

Cats - Type 2
Dogs - type 1

Question 12

What is insulin resistance?

Answer 12

the diminished ability of cells to respond to the action of insulin in transporting glucose from the blood into tissues

Question 13

Why does obesity lead to insulin resistance?

Answer 13

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

Question 14

What is amyloid polypeptide/amylin and how does it cause diabetes mellitus?

Answer 14

Co-secreted with insulin by FELINE beta cells

Question 15

What are the types of diabetes when classified by therapy requirements

Answer 15

Insulin-dependent diabetes mellitus (IDDM) - Type 1
Non-insulin dependent diabetes mellitus (NIDDM) - Type 2

Question 16

Describe insulin-dependent diabetes mellitus (IDDM)

Answer 16

Type 1 DM
Most common form of diabetes
~100% in dogs
50-70% in cats
Permanent insulin deficiency
Animal needs exogenous insulin

Question 17

Describe non-insulin dependent diabetes mellitus (NIDDM)

Answer 17

Type 2 DM
Common in cats - obesity induced insulin resistance
Dogs (rare):
- insulin-antagonism
- drugs - glucocorticoids, progestogens
- conditions - dioestrus

Question 18

Describe EMS (equine metabolic syndrome)

Answer 18

Insulin resistance
Most common clinical sign = laminitis
High levels of insulin and glucose seen in EMS

Question 19

What are the most common clinical signs of diabetes mellitus?

Answer 19

PU/PD
Polyphagia
Weight loss

Question 20

Why does diabetes mellitus cause PU/PD?

Answer 20

Osmotic diuresis:
- Blood glucose exceeds ‘renal threshold’
- Glucose acts as osmotic particle
- Draws water into renal tubule => dilutes urine and increases urine volume

Question 21

Why does diabetes mellitus cause polyphagia?

Answer 21

Lack of insulin => glucose cannot enter satiety center in hypothalamus (GLUT4 needs insulin to work) => failure to inhibit appetite centre => polyphagia despite hyperglycaemia

Question 22

Why does diabetes mellitus cause weight loss?

Answer 22

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

Question 23

Why does diabetes mellitus cause cataracts?

Answer 23

Glucose uptake into lens => lactate => diffuses out
EXCESS glucose => fructose and sorbitol => do not diffuse => trapped => draw water into lens

Question 24

Why does diabetes mellitus cause ketoacidosis?

Answer 24

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

Question 25

what diagnostic tests can used to diagnose diabetes mellitus?

Answer 25

Blood glucose
Glucosuria
Fructosamine
Mobilisation of fatty acids from adipose tissue:
- hypercholesterolemia
- hypertriglyceridemia
- visible lipid in serum/plasma
Hepatic lipidosis:
- increased lipid enzymes
Urinalysis

Question 26

How does fructosamine diagnose diabetes mellitus

Answer 26

Proteins in blood circulate and pick up glucose - this protein/glucose level can be measured
Fructosamine reflects previous 2-3 weeks of blood glucose

Question 27

Fill in this table showing how to differentiate between diabetes mellitus and stress

Answer 27

Question 28

How can urinalysis be used to diagnose diabetes mellitus?

Answer 28

USG >1.025 (increased by glucosuria)
Glucose
+/- ketones