Diabetes Mellitus

Question 1

How may diabetes be diagnosed?

Answer 1

One abnormal plasma glucose level in the presence of symptoms, two elevated fasting venous plasma glucose samples in asymptomatic individuals, abnormal glucose tolerance test and elevated HbA1c

Question 2

How may metformin be used in the treatment of diabetes?

Answer 2

This is a biguanide drug that inhibits gluconeogenesis as well as increasing the sensitivity of the liver to insulin and increasing the levels of GLP-1

Question 3

What is the function of GLP-1?

Answer 3

It facilitates increased metabolic rate and decreased appetite

Question 4

How may sitagliptin be used in the treatment of diabetes?

Answer 4

Sitagliptin is a DDP-4 inhibitor, an enzyme that ordinarily catalyses the breakdown of GLP-1, and therefore this allows GLP-1 to act for longer to reduce appetite and increase metabolic rate in order to increase insulin sensitivity in the tissues

Question 5

Name two ketone bodies

Answer 5

Acetoacetate and beta-hydroxybutarate

Question 6

How can diabetes lead to ketoacidosis?

Answer 6

The lack of insulin means that glucose can’t be taken up, and therefore the body begins to utilise fat stores via lipolysis, this leads to an increased amount of beta oxidation and a resultant acetyl-CoA accumulation which are used in the liver to produce ketone bodies, which have an acidic property, which leads to the development of an acidosis if unresolved.

Question 7

Why may a diabetic experience complications due to hypoglycaemia?

Answer 7

Excessive alcohol consumption can inhibit gluconeogenesis at the level of LDH, insulinomas (tumour of the pancreatic beta cells which activates GK mutations), excessive exercise, reactive hypoglycaemia (excess insulin response to a high carbohydrate meal in pre-diabetes) and poorly managed type 1 diabetes with high insulin dose injection.

Question 8

Aside from glucagon, what other hormones are secreted in response to hypoglycaemia?

Answer 8

Growth hormone, cortisol and adrenaline. GH and cortisol decrease the rate of glucose utilisation and promote fat utilisation as the sole source of energy

Question 9

What are the symptoms of hypoglycaemia?

Answer 9

Autonomic symptoms arise first including sweating, palpitations, trembling, anxiety and hunger. Thereafter neuroglycopaenic symptoms arise which can include confusion, weakness, drowsiness and difficulty concentrating, if the condition is allowed to progress this can eventually lead to convulsion, fitting, seizures and coma.

Question 10

What are the microvascular complications of hyperglycaemia?

Answer 10

Kidney disease, nerve disease, blindness and amputation

Question 11

When glucose is in excess it is diverted to other pathways, name four of them.

Answer 11

The polyol pathway (produces sorbitol), hexosamine pathway, protein kinase C pathway and AGE pathway

Question 12

How may hyper activation of protein kinase C due to hyperglycaemia lead to microvascular damage in diabetics?

Answer 12

Hyperactivation of protein kinase C can lead to damage of the blood vessels such as increased permeability, increased occlusion, increase ROS levels, increased inflammation and mitochondrial dysfunction

Question 13

What is meant by ‘dyslipidaemia’?

Answer 13

The ectopic fat deposition in the skeletal muscle and liver

Question 14

What is diabetic retinopathy?

Answer 14

A disease of the retina which involves damage to the blood vessels in the back of the eye

Question 15

What are the two types of diabetic retinopathy?

Answer 15

Proliferative and non-proliferative

Question 16

Describe non-proliferative diabetic retinopathy

Answer 16

This is where there is dilation of the retinal veins and micro aneurysms form, which causes an internal haemorrhage and oedema to form in the retina. This oedema in the central retina is the main cause of vision loss

Question 17

Describe proliferative diabetic retinopathy

Answer 17

This is where fragile, new blood vessels form near the optic disc and grow on the vitreous chamber and elsewhere in the retina. If one of these fragile vessels becomes damage they can bleed, reduce vision and lead to the separation and detachment of areas of the retina

Question 18

Describe proliferative diabetic retinopathy

Answer 18

This is where fragile, new blood vessels form near the optic disc and grow on the vitreous chamber and elsewhere in the retina. If one of these fragile vessels becomes damage they can bleed, reduce vision and lead to the separation and detachment of areas of the retina

Question 19

What is diabetic nephropathy?

Answer 19

A kidney disease that involves damage to the blood vessels of the glomeruli and is characterised by proteinusria, glomerular hypertrophy, decreased GFR and renal fibrosis

Question 20

What is diabetic neuropathy?

Answer 20

This involves damage to the nerve fibres and blood vessels that supply the nerves

Question 21

What different types of diabetic neuropathy can you get?

Answer 21

Peripheral - damage to peripheral nerves
Proximal - pain in the thighs/hips and leg weakness
Autonomic - affects autonomic innervation
Focal - affects any nerve in the body

Question 22

How does diabetes contribute to atherosclerotic plaque formation?

Answer 22

The formation of advanced glycation end productions promotes atherosclerosis; AGE modification of oxidised LDL receptors leads to enhanced LDL uptake into atherosclerotic plaques. In addition, AGE-LDL causes pro-inflammatory cytokine production and the glycation of apolipoproteins impairs removal of cholesterol from atherosclerotic plaques.

Question 23

What is type 1 diabetes?

Answer 23

An absolute insulin deficiency that is characterised by T-cell mediated disruption the pancreatic beta cells in the Islets of Langerhans

Question 24

What is type 2 diabetes?

Answer 24

This is the most common form of diabetes and it’s a chronic and progressive disease characterised by the abnormal action and secretion of insulin

Question 25

What are the risk factors for type 2 diabetes?

Answer 25

Obesity, family history, age and ethnicity

Question 26

What molecular mechanisms may underlie the development of insulin resistance?

Answer 26

DAG (diacylglycerol) from fatty acids can induce the activation of protein kinase C which can phosphorylate the threonine and serine residues in the IRS complex which prevents binding of the IRS complex to the IR and therefore prevents the signalling cascade from progressing