Diabetes Mellitus

Question 1

What does DM ultimately lead to?

Answer 1

Leads to damage of small and large blood vessels (cardiovascular system)

Question 2

What is DM characterised by?

Answer 2

Hyperglycaemia

Question 3

Why does glucose rise in DM?

Answer 3

Inability to produce insulin due to beta cell failure (type 1 mainly just this) and/or
Insulin production adequate but insulin resistance prevents it working effectively.

Question 4

What happens in type 1?

Answer 4

Genetic predisposition interacts with environmental trigger to produce killer lymphocytes and macrophages and antibodies that attack and progressively destroy beta cells (autoimmune destruction).

Question 5

What are the three main symptoms of type 1?

Answer 5

Polyuria
Polydipsia
Weight loss

Question 6

What is polyuria and why does it occur in diabetes?

Answer 6

Excessive urination. Large quantities of glucose in blood are filtered by kidney, not all reabsorbed. Extra glucose in nephron places extra osmotic load on it, meaning less water is reabsorbed to maintain osmotic pressure.

Question 7

How can you distinguish between type 1 and 2?

Answer 7

Type 1 will have ketones in the urine

Question 8

What can excess ketones in the body cause?

Answer 8

Ketoacidosis due to the H+ associated with the ketones. This is dangerous and can kill v rapidly so it is treated first if someone presents

Question 9

Why do type 1 and not type 2 produce ketones?

Answer 9

Type 1 cant metabolise glucose and so body finds other ways to generate energy, eg lipolysis. Produces lots of FAs and ketones are produced from an excess of these.
Type 2 can still metabolise glucose as beta cells still producing some insulin which is not enough to control glucose level but can suppress lipolysis.

Question 10

What does a lack of insulin cause?

Answer 10

Decreased uptake of glucose into adipose tissue and skeletal muscle.
Decreased storage of glucose as glycogen in muscle and liver.
Increased gluconeogenesis in liver.
High glucose levels in urine.

Question 11

What happens in type 2?

Answer 11

Obesity leads to insulin resistance. This leads to secretion of more insulin to maintain the glucose level in the blood. However, after time the pancreas can no longer keep up, pancreatic exhaustion, and hyperglycaemia develops. The pancreas is going at full speed and cant accelerate anymore so the body can regulate glucose as well.

Question 12

Why else may beta cells fail in type 2?

Answer 12

Linked to obesity, fat can sit and cause inflammation in the body, eg in the pancreas which can cause beta cell failure over time.

Question 13

What are the differences between type 1 and 2? Age, characteristics, time, insulin?

Answer 13

Type 1- most common in the young, progressive loss of all/most beta cells, rapidly fatal if not treated, must have insulin.
Type 2- usually older, slow progressive loss of beta cells but with disorders of insulin secretion and tissue resistance, may be present for a long time before diagnosis, may not need insulin initially but will do eventually.

Question 14

What are the symptoms of type 1?

Answer 14

Rapid onset, unexplained weight loss, polyuria, polydipsia, often extremely ill (immunodepressed)
Late presentation- may be vomiting due to ketoacidosis. Kidney failure.

Question 15

How would you diagnose DM?

Answer 15

Symptoms +
Random venous plasma glucose concentration (more than 11.1mM/l) or
Fasting plasma glucose concentration (more than 7mM/l) or
Oral glucose tolerance test, fasting level before then random one after 2hrs and 75g anhydrous glucose
HbA1C (more than 6.5) type 2 only

Question 16

What can you only use to measure type 2? What is it?

Answer 16

HbA1C
Measure amount of glucose attached to the RBCs.
RBCs can circulate for weeks and so shows the glucose levels for the time the RBCs have been circulating.

Question 17

Why do ketone bodies form?

Answer 17

High rates of beta oxidation of fats in the liver coupled to the low insulin/anti-insulin ratio leads to production of huge amounts of ketone bodies.

Question 18

When can hypoglycaemia occur?

Answer 18

Increased activity, missed meal, overdose of insulin.

Question 19

What are the symptoms of hypoglycaemia?

Answer 19

Sweating, anxiety, hunger, tremor, palpitations, confusion, drowsiness, seizures, coma.

Question 20

What are the symptoms of hyperglycaemia?

Answer 20

Polyuria, polydipsia, weight loss, fatigue, blurred vision, dry or itchy skin, poor wound healing, plasma proteins may become glycosylated.

Question 21

How do you treat type 1?

Answer 21

Insulin injected subcutaneously as is a peptide hormone that would be digested in the stomach. Frequent blood glucose measurement.

Question 22

How do you treat type 2?

Answer 22

First diet and lifestyle changes - reduce intake of glucose, exercise increases bodys sensitivity to insulin.
Then drugs - eg metformin
Eventually they will need insulin

Question 23

How do insulin and glucagon act?

Answer 23

With cell surface receptors on target cells.

Question 24

How can glucagon and insulin be inactivated?

Answer 24

Receptor with hormone bound can be internalised. They act by binding to receptors on the outside of the cell and so if they are inside they can bind so they become inactive.

Question 25

How is insulin secreted from beta cells?

Answer 25

High plasma glucose causes insulin secretion.
Increased glucose in ecf is a stimulus for insulin release.
Glucose transported into beta cell by facilitated diffusion through GLUT2.
Increase glucose in ecf leads to increased conc in beta cell.
This leads to membrane depolarisation as Katp channels open and there is an influx of extracellular calcium via voltage gated calcium channel.
Increase in calcium in beta cell triggers exocytosis of insulin containing secretory granules.

Question 26

What is the only thing that stimulates insulin AND glucagon?

Answer 26

Increase in aas. Insulin wants to build them into proteins and glucagon wants to use them for gluconeogenesis.

Question 27

What is the insulin receptor?

Answer 27

Dimer, 2 identical subunits that span the cell membrane.
Each subunit made up of 1 alpha and 1 beta chain connected by a disulphide bond.
Alpha chain is on the exterior and binds to the insulin, beta chain spans the cell membrane.

Question 28

How is the insulin receptor activated?

Answer 28

Alpha chains move together when insulin is detected and fold around the insulin.
This moves the beta chains together making them an active tyrosine kinase. Initiates phosphorylation cascade which results in increased GLUT4 expression which is then put into the membrane (a channel that increases the amount of glucose taken in by the cell).

Question 29

What happens if insulin doesnt bind to the receptors?

Answer 29

No GLUT4 put into membrane so no extra glucose can be drawn into cell.

Question 30

How does glucagon get secreted?

Answer 30

Decreased glucose in alpha cells (due to decreased glucose in blood) causes glucagon that has been synthesised in the rough er, transported to golgi, packaged into granules, moved to cell surface to be secreted. Marginisation happens where the vesicle moves towards the cell surface and then exocytosis occurs where the vesicle membrane and plasma membrane fuse and release the contents.

Question 31

What are the macrovascular complications of DM?

Answer 31

Increased risk of stroke
Increased risk of MI
Poor circulation to periphery

Question 32

Why does DM cause kidney failure?

Answer 32

Increased glucose in the blood puts pressure on the kidneys as they have to work at a faster rate as it attempts to excrete it out which can lead to renal shock leading to kidney failure.

Question 33

What kind of disorders is DM a group of?

Answer 33

Metabolic

Question 34

What microvascular complications can occur as a result of DM?

Answer 34

Eye disease due to osmotic effects of glucose
Retinopathy due to damage of blood vessels in retina
Nephropathy
Neuropathy
Feet, poor blood supply, damage to nerves and increased risk of infection

Question 35

What is neohropathy due to?

Answer 35

Damage to the glomeruli, poor blood supply because of change in kidney blood vessels, or damage from infections of the urinary tract.

Question 36

Why are infections common in diabetics?

Answer 36

Excess glucose for bacteria to thrive

Question 37

What is neuropathy due to?

Answer 37

Damage to peripheral nerves which directly absorb glucose causing changes to or loss of sensation and changes due to alteration of function of ANS.