Diabetes

Question 1

What are the symptoms of TIIDM?

Answer 1

Polydypsia.
Polyuria.
Polyphagia.
Weight loss.

Question 2

How would you diagnose TIIDM?

Answer 2

OGTT = > 11.1mmol/L.
Fasting glucose = > 7mmol/L.
HbA1c = > 48mmol/L or > 6.5%.

Question 3

What factors may affect HbA1c?

Answer 3

Haemolysis.
Iron deficiency anaemia.
Renal impairment (i.e. reduced EPO).
Pregnancy (increased RBC turnover).
Blood transfusion.

Question 4

Where is insulin produced?

Answer 4

Beta cells of the pancreas.

Question 5

What are the main functions of insulin?

Answer 5

Stimulates uptake of glucose by peripheral tissue > reduced blood glucose.
Inhibits liver breakdown of glycogen & increases glycogenesis.
Increases protein synthesis.
Increases TG storage in adipose tissue.

Question 6

Explain the mechanism of insulin secretion?

Answer 6

Glucose binds to the GLUT-2 receptor on beta cells.
Glucose forms ATP via glycolysis.
Increased ATP > closure ATP-sensitive K+ channels > depolarisation.
Depolarisation > opening of voltage-gated Ca2+ channels.
Ca2+ influx > insulin release.

Question 7

Why is it difficult to measure blood insulin levels? What can be measured instead?

Answer 7

Insulin undergoes extensive first pass metabolism.

Measure C-peptide.

Question 8

Where is glucagon produced?

Answer 8

Alpha cells of the pancreas.

Question 9

What are the main functions of glucagon?

Answer 9

Releases glucose into blood.

Stimulates gluconeogenesis & glycogenolysis.

Question 10

Where an incretins produced?

Answer 10

Intestinal L-cells of the ileum.

Question 11

What are the main functions of incretins?

Answer 11

Bind to GLP-1 receptor on beta cells > insulin release.

Decrease glucagon release from alpha cells.

Question 12

Explain how insulin causes glucose uptake in peripheral tissue?

Answer 12

Insulin binds to the insulin receptor > phosphorylation of PI-3K > expression of GLUT-4 transporter proteins on the cell surface > glucose uptake.

Question 13

Explain how insulin resistance occurs in TIIDM?

Answer 13

Insulin binds to the insulin receptor > impaired PI-3K phosphorylation > GLUT-4 is not transported to the cell surface > no glucose uptake.

Question 14

Explain how insulin resistance progresses?

Answer 14

Insulin resistance > reduced glucose uptake > hyperinsulinaemia > further resistance > hyperglycaemia > glucotoxicity > impaired B-cell function > impaired insulin secretion.

Question 15

What happens to glucagon secretion in TIIDM?

Answer 15

Glucagon secretion is increased > hyperglycaemia.

Question 16

Explain the role of the kidneys in TIIDM?

Answer 16

Increased filtration of blood glucose ( > 10mmol/L) > increased expression of SGLT-2 receptors > increased glucose reabsorption > hyperglycaemia.

Question 17

Explain the role of adipose cells in TIIDM?

Answer 17

Adipose cells are resistant to insulins anti-lipolytic effects > lipolysis > increased plasma FFAs.

Chronically elevated plasma FFAs results in:
> Increased gluconeogensis.
> Hepatic/peripheral insulin resistance.
> Impaired insulin secretion.

Question 18

Explain the role of adipose cells in TIIDM?

Answer 18

Adipose cells are resistant to the effects of insulin > lipolysis > increased plasma FFAs.

Chronically elevated plasma FFAs results in:
> Increased gluconeogensis.
> Hepatic/peripheral insulin resistance.
> Impaired insulin secretion.

Question 19

What are the effects of hypoinsulinaemia?

Answer 19

Proteolysis in skeletal muscle > muscle wasting & weight loss.
TG breakdown in adipose tissue > increased FFAs & ketones.
Glycogenolysis in the liver > hyperglycaemia.

Question 20

What are the effects of hypoinsulinaemia?

Answer 20

Proteolysis in skeletal muscle > muscle wasting & weight loss.
TG breakdown in adipose tissue > increased FFAs & ketones.
Glycogenolysis in the liver > hyperglycaemia.

Question 21

What factors help differentiate between TIDM & TIIDM?

Answer 21

Ketoacidosis:
> Only usually occurs in TIDM due to no insulin production.

FH of diabetes:
> Suggests TIDM.

Obesity:
> Mainly associated with TIIDM.