Diabetes

Question 1

Define diabetes.

Answer 1

An inordinate and persistent increase in urinary output.

Question 2

Define insipidus.

Answer 2

Glucose is not present in the urine.

Question 3

Define mellitus.

Answer 3

Glucose is present in the urine.

Question 4

Explain diabetes insipidus.

Answer 4

Copious volumes of v dilute urine (polyuria)
Polydipsia.
NO CHANGE IN URINARY GLUCOSE.
Deficient in production and release of ADH (vasopressin) from the PP. THerefore the CD is impermeable to water and there is no reasborption - all lost in the urine.

Question 5

How would you treat diabetes insipidus?

Answer 5

Desmopression a V2 receptor agonist (analogue of ADH).

Question 6

Type 1 diabetes?

Answer 6

Insulin independent diabetes mellitus.
10%
Low levels of absence of circulating insulin.

Question 7

Type 2 diabetes?

Answer 7

Non-insulin dependent diabetes mellitus.
90%
Reduced response to insulin.
Insulin resistance.
Insulin overproduced.

Question 8

Symptoms of diabetes mellitus?

Answer 8

Elevated blood glucose >11mM (fasted conc approx 7mM) = elevated urinary glucose.
Renal transport maximum 100-175mg/min…increased urination.

Question 9

Explain how untreated diabetes mellitus can cause damage to the nerve/lens

Answer 9

Glucose reduced to sorbital - osmotic damage

Glycosylation of alpha-crystallin - cataracts

Question 10

Explain how untreated diabetes mellitus can cause damage to erythrocytes.

Answer 10

glycosylation of haemoglobin A1C. Oxygen then can’t be released. Normal = 5-8%. Abnormal - 12-15%.
As erythrocytes last 120 days…gives an indication how well BGL has been managed in the last few weeks.

Question 11

Name 6 complications of untreated DM.

Answer 11

Diabetic retinopathy.
Diabetic nephropathy.
Diabetic neuropathy.
Infection.
CV disease (heart disease, peripheral vascular disease, gangrene)
Diabetic coma.

Question 12

Describe a diabetic coma…

Answer 12

HIGH BLOOD GLUCOSE…
…ketosis (increase fat metabolism, increase acetyl coA, ketones formed = metabolic acidosis, stimulates respiratory centres, deep sighing breathing).

…OSMOTIC DIURESIS
Decreased plasma volume, decrease BP, decrease GFR, increase K, increase plasma in urine.

Question 13

Epidemiology of DM?

Answer 13

Type 1 - varies in different countries. NOT all genetically determined.

Type 2 - 85% obese, larger genetic component. Triggered by obesity?
6th leading cause of death and leading cause of blindness.

Question 14

Explain how indulin is formed.

Answer 14

From pro-insuline. A chain and B chain linked by C peptide and attached to each other by disulphide bonds.
C peptide is cleaved.
A chain: 30aa
B chain: 21aa.

Question 15

What do A cells of the pancreas secrete?

Answer 15

glucagon and glucagon like peptides.

Question 16

What do B cells of the pancreas secrete?

Answer 16

insulin, c peptide and amylin

Question 17

What do D cells of the pancreas secrete?

Answer 17

Somatostatin.

Question 18

What do F cells of the pancreas secrete?

Answer 18

Pancreatic polypeptide.

Question 19

Explain the regulation of insulin release.

Answer 19

1) Glucose enters beta cells via Glut-2.
2) Glucose is metabolised. Increase in ATP.
3) ATP sensitive K channels shut.
4) Cell depolarises.
5) VOCC open
6) Ca++ influx
7) Insulin containing granules are released by exocytosis.

Question 20

Why is the release of insulin normally biphasic?

Answer 20

Rapid - release of preformed insulin,

Secondary increase - cleaved preformed precursor - slower response.

Question 21

What factors stimulate insulin release?

Answer 21

Glucose
AA
FA
Sympathetic B2 stimulation
Parasympathetic stimulation.
Oral glucose (more so than iv glucose...due to incretins...GLP-1, GIP etc).

Question 22

What factors inhibit insulin release?

Answer 22

A2 receptors
somatostatin
high amylin concentrations.
galanin.

Question 23

Describe the insulin receptor.

Answer 23

Tyrosine kinase receptor - dimer. Extracellular alpha subunit and intracellular beta subunit. When insulin binds…Conformational change in beta sub unit…results in autophosphorylation.

Question 24

What is the action of insulin?

Answer 24

Increase glucose in cells by causing glut 4 (insulin sensitive) receptors to be inserted in the membrane

Question 25

What effect does insulin have on CHO metabolism in adipose, liver and muscle cells?

Answer 25

Adipose: Stimulate glucose uptake and stimulate glycerol synthesis.
Liver: increased glycolysis, increase glycogenesis, decrease gluconeogensis and decreased glycogenolysis
Muscle: increase glucose uptake, increase glycogenesis and decrease glycogenolysis.

Question 26

What effect does insulin have on fat metabolism in adipose and liver cells.

Answer 26

Adipose: Increase TG synthesis, decrease FA synthesis, decrease lipolysis.
Liver: increase lipogenesis and decrease lipolysis

Question 27

What effect does insulin have on protein metabolism in liver and muscle cells?

Answer 27

Liver: decrease protein breakdown
Muscle: increase protein synthesis and increase aa uptake.

Question 28

What is 1 unit of insulin.

Answer 28

The amount required to lower a fasted rabbits blood glucose to 2.5mM.
approx 36mg of insulin.

Question 29

Describe the differences between porcine, bovine and human insulins.

Answer 29

Porcine - 1 aa different to human,
Bovine - 3 aa different to human,
Differences in aa between humans - determines differential duration of action.

Question 30

Why do we have insulin zinc suspensions?

Answer 30

Insulin naturally forms crystals and zinc encourages this…longer duration and crystals don’t dissolve.

Question 31

What are the main side effects of insulin preparations?

Answer 31

HYPOGLYCEMIA.

Neuroglycopenia - lack of glucose to brain. if severe - glucose, glucagon or adrenaline (iv)