Session 7: Diabetes mellitus

Question 1

Definition of Diabetes mellitus.

Answer 1

Group of metabolic disorders characterised by chronic hyperglycaemia.

Due to insulin deficiceny, insulin resistance or both.

Question 2

Fill in blank spaces

Answer 2

Question 3

Briefly explain the staging of type 1 diabetes.

Answer 3

HLA markers and auto-antibodies from genetics without glucose or insulin abnormalities.

May develop imparied glucose tolerance and later on diabetes before they finally become totally insulin resistant.

Effectively T Killer cells kill of beta-cells in islets of langerhans

Question 4

Briefly explain staging of Type 2 diabetes.

Answer 4

Found with insulin resistance.

Insulin production failure may ensue and impaired glucose tolerance.

Finally development of diabetes occur that will be managed with diet -> tablets -> insulin.

Question 5

What is the genetic predisposition of Type 1 diabetes associated with?

Answer 5

HLA DR3 and HLA DR4

Question 6

Type 1 diabetes usually present in a young person with a recent history of viral infection.

There is a triad of symptoms which they present. What are the symptoms?

Answer 6

Polyuria

Polydipsia

Weight loss

Question 7

Why does polyuria occur in type 1 diabetes?

Answer 7

Polyuria is excess urine production.

Since there is an excess of glucose in the bloodstream of a patient with type 1 diabetes the threshold of the renal system will be met and exceeded. This means that not all glucose will be reabsorbed into the system from the kidney.

Glucose will remain in the kidney. Since glucose is osmotically active this means that water will not be reabsorbed into blood stream and remain in the kidney.

This leads to an increased excretion of urine.

Question 8

Why does polydipsia occur in type 1 diabetes?

Answer 8

Polydipsia means excess of drinking which comes from thirst.

Thirst comes from the polyuria where the patient excretes an excess of urine and water.

Question 9

Why does weight loss occur in type 1 diabetes?

Answer 9

Fat and proteins are metabolised in the absence of insulin.

Question 10

How can you detect type 1 diabetes?

Answer 10

They suffer from glycosuria which means that there is a presence of glucose in the urine.

Question 11

If type 1 is left untreated it can be rapidly fatal. Why?

Answer 11

Because of the absence of insulin there will be an increased metabolism of fats and proteins.

High rates of beta-oxidation produce ketone bodies from acetyl CoA like acetoacetate and beta-hydroxybutyrate + acetone.

The accumulation of ketone bodies causes the pH to decrease which can eventually lead ketosis and if left untreated keto-acidosis.

Question 12

Give features of keto-acidosis.

Answer 12

Prostration

Hyperventilation

Nausea

Vomiting

Dehydration

Abdominal pain

Question 13

How do you test for ketosis and keto-acidosis?

Answer 13

For ketone bodies present in urine.

Patients may also have a sweet-smelly breath due to acetone.

Question 14

Risk factors of type 2 diabetes.

Answer 14

Age

Obesity

Genetic predispositions

Question 15

What are common clinical features of diabetes type 2.

Answer 15

Patients may present with the classical triad of symptoms (polyuria, polydipsia and weight loss)

However it is more common to present with a variety of symptoms:

Lack of energy
Persistent infections
Thrush infections of genitalia
Infections of feet
Slow healing of minor skin damage
Visual impairment

Question 16

Apart from symptoms, how is diabetes diagnosed?

Answer 16

There are three test that can be done and should be done.

A random venous plasma glucose concentration

A fasting plasma glucose concentration

Plasme glucose concentration after 75g of anhydrous glucose in oral glucose tolerance test (OGTT)

Question 17

Cut off point of:

Random venous plasma glucose concentration

Fasting plasma glucose concentration

OGTT

Answer 17

Random: > or equal to 11.1 mmol/L

Fasting: > or equal to 7.0 mmol/L

OGTT: >11.1 mmol/L 2 hours after

Question 18

Management of type 1 diabetes.

Answer 18

There is no cure.
Type 1 needs frequent injections of insulin.

Patients need to be educated, the risk factors of their conditions and how it can progress daily/weekly.

Dietary management and regular exercise.

Check blood glucose by blood from finger prick.

Question 19

Why might a type 1 diabetes patient develop keto-acidosis even though they manage their disease?

Answer 19

Infection or trauma can increase the risk of developing keto-acidosis so increased insulin might have to be injected.

Question 20

What are other risks of a patient self-managing their diabetes?

Answer 20

Excess or too frequent injection of insulin can cause hypoglycaemia which can be fatal if patient isn’t treated by glucose either by mouth or infusion.

Question 21

Give tissues that are of particular risk of damage in the existence of peristent hyperglycaemia.

Answer 21

Peripheral nerves

The eye

Kidneys (glomerulus and efferent/afferent vessels going into glomerulus)

Question 22

Why are these sites susceptible to damage from hyperglycaemia.

Answer 22

Because they don’t need insulin to transport glucose intracellularly.

This means that as the rest of the body doesn’t take up more glucose in diabetes when insulin isn’t present, the eye, peripheral nerves and kidneys will still take up glucose, and in an increased amount.

Question 23

Why is the increased uptake of glucose a problem of these tissues?

Answer 23

Because the glucose will metabolised via an enzyme called aldose reductase which catalyses the reaction:

Glucose + NADPH + H+ —-> Sorbitol and NADP+

This means that the NADPH stores will deplete and inappropriate disulphide bonds will form in the cellular proteins which alters their structure and functions. This causes damage to these tissues.

Also the accumulation of sorbitol causes osmotic damage to cells.

Question 24

Why is increased glycation caused by peristent hyperglycaemia?

Answer 24

Increased glycation of plasma proteins leads to disturbances in their function.

Glucose reacts with free amino groups in proteins to form stable covalent linkages this causes defective protein function.

Question 25

What is glycated haemoglobin (HbA1c)?

Answer 25

Glucose reacts with terminal valine of haemoglobin, this produces HbA1c.

Question 26

Why is HbA1c clinically important?

Answer 26

Because RBCs last around 120 days in the bloodstream.

THis means that the percentage of glycated haemoglobin is a good indicator of how effective blood glucose control has been during 2-3 months.

This means that HbA1c is related to the average blood glucose concentration over the preceding 2-3 months.

Question 27

How much haemoglobin is glycated in a normal healthy individual?

How much in a poorly controlled diabetic?

Answer 27

4-6%

Can exceed 10%

Question 28

Give the two classifications of clinical complications due to diabetes.

Answer 28

Macrovascular complications

Microvascular complications

Question 29

What macrovascular complications can occur due to diabetes?

Answer 29

Increased risk of stroke

Increased risk of myocardial infarctions

Poor circulation to the periphery (feet in particular)

Question 30

What microvascular complications might occur due to diabetes?

Answer 30

Diabetic eye disease

Diabetic kidney disease

Diabetic neuropathy

Diabetic feet

Question 31

Why would microvascular and macrovascular complications occur due to diabetes?

Answer 31

As the disease progresses with will get worse.

However this is mostly due to poor glucose conc. control.

Question 32

Why can diabetic eye disease arise?

Answer 32

Osmotic effects of glucose due to its accumulation in the eye as insulin isn’t needed here for uptake. Leading to glaucoma where glucose is broken down into sorbitol, sorbitol which is osmotically active.

Also more importantly it can lead to diabetic retinopathy where damage to blood vessels in the retina can lead to blindness.
Damaged blood vessels can leak and form protein exudates on retina, or they can rupture and cause bleeding into the eye. New vessels can form but they are usually very weak.

Question 33

Why can diabetic kidney disease arise?

What are early signs of nephropathy?

Answer 33

Damage to glomeruli, which don’t need insulin either to take up glucose.

Also poor blood supply from afferent and efferent blood vessels to glomeruli will damage the glomeruli.

Diabetics are more susceptible to UTIs which can lead to kidney daamge as well.

Early signs: An increased amount of protein in the urine.

Question 34

How can diabetic neuropathy arise?

Complications?

Answer 34

As in previous cases peripheral nerves don’t need insulin to take up glucose. This causes accumulation of glucose and damages peripheral nerves.

This can lead to loss of sensation and alteration in the function of the autonomic nervous system.

Question 35

How can diabetic feet arise?

Answer 35

Due to poor blood supply, damage to nerves and increased risk of infection all make the extremities and especially feet susceptible to damage.

Question 36

Define metabolic syndrome.

Answer 36

A group of symptoms including insulin resistance, dyslipidaemia, glucose intolerance and hypertension associated with central adiposity.

The co-occurence of a number of cardiovascular risk factors like dyslipidaemia, hypertension, obesity and sedentary lifestyle in the same individual can be classified as metabolic syndrome.

Question 37

How is diabetes related to dyslipidaemia?

Answer 37

Dyslipidaemia can develop from diabetes type 2 where there is an increase in VLDL, LDL and a decrease in HDL.

This in its turn makes the individual more prone to cardivascular disease as they are susceptible of atherosclerosis. LDLs get oxidised and trapped and will form foam cells in vascular walls leading to atherosclerosis.

Question 38

Explain how ATP dependent potassium channels are important in the role of insulin secretion.

Answer 38

Glucose is taken up by beta-cells and metabolised. ATP will inactivate KATP channels cuasing the membrane to depolarise.

Depolarisation of the membrane causes voltage-gated Ca2+ channels to open and Ca2+ enters the beta-cell. This stimulates the secretion of insulin.