Session 7: Diabetes mellitus Flashcards
Definition of Diabetes mellitus.
Group of metabolic disorders characterised by chronic hyperglycaemia.
Due to insulin deficiceny, insulin resistance or both.
Fill in blank spaces
Briefly explain the staging of type 1 diabetes.
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
Briefly explain staging of Type 2 diabetes.
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.
What is the genetic predisposition of Type 1 diabetes associated with?
HLA DR3 and HLA DR4
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?
Polyuria
Polydipsia
Weight loss
Why does polyuria occur in type 1 diabetes?
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.
Why does polydipsia occur in type 1 diabetes?
Polydipsia means excess of drinking which comes from thirst.
Thirst comes from the polyuria where the patient excretes an excess of urine and water.
Why does weight loss occur in type 1 diabetes?
Fat and proteins are metabolised in the absence of insulin.
How can you detect type 1 diabetes?
They suffer from glycosuria which means that there is a presence of glucose in the urine.
If type 1 is left untreated it can be rapidly fatal. Why?
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.
Give features of keto-acidosis.
Prostration
Hyperventilation
Nausea
Vomiting
Dehydration
Abdominal pain
How do you test for ketosis and keto-acidosis?
For ketone bodies present in urine.
Patients may also have a sweet-smelly breath due to acetone.
Risk factors of type 2 diabetes.
Age
Obesity
Genetic predispositions
What are common clinical features of diabetes type 2.
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
Apart from symptoms, how is diabetes diagnosed?
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)
Cut off point of:
Random venous plasma glucose concentration
Fasting plasma glucose concentration
OGTT
Random: > or equal to 11.1 mmol/L
Fasting: > or equal to 7.0 mmol/L
OGTT: >11.1 mmol/L 2 hours after
Management of type 1 diabetes.
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.
Why might a type 1 diabetes patient develop keto-acidosis even though they manage their disease?
Infection or trauma can increase the risk of developing keto-acidosis so increased insulin might have to be injected.
What are other risks of a patient self-managing their diabetes?
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.
Give tissues that are of particular risk of damage in the existence of peristent hyperglycaemia.
Peripheral nerves
The eye
Kidneys (glomerulus and efferent/afferent vessels going into glomerulus)
Why are these sites susceptible to damage from hyperglycaemia.
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.
Why is the increased uptake of glucose a problem of these tissues?
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.
Why is increased glycation caused by peristent hyperglycaemia?
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.
