Diabetes Flashcards
1
Q
List 3 differences between Type I and Type II DM
A
- Type I is insulin dependant, Type II is non-insulin dependant
- Type I is defined by an absolute lack of insulin, Type II can still produce insulin but cells are less responsive
- Type I can cause ketoacidosis
2
Q
What can cause a rise in blood glucose?
A
- Inability to produce insulin due to β cell failure or autoimmune destruction
- Insulin resistance of cells so glucose cannot be utilised
3
Q
Name 4 typical symptoms of hyperglycaemia
A
- Polyuria
- Polydipsia
- Urogenital infections
- Blurring of vision
4
Q
What are the symptoms of inadequate energy utilisation?
A
- Tiredness
- Lethargy
- Weakness
- Unexplained weight loss (due to increased metabolism of fatty acids)
5
Q
What tests could you perform to help diagnose diabetes?
A
- Fasting blood glucose
- Oral glucose tolerance test
- HbA1c (Type II only)
- Need symptoms and 1 abnormal test (2 if asymptomatic) to be diagnosed
6
Q
What is the advantage of performing a HbA1c test on a person with Type II DM?
A
- GLYCATION of Haemoglobin in RBC due to high plasma glucose
- Lifespan of RBC is ~120 days
- Gives % reading of blood glucose levels (glucose saturation) over the past 120 days
- Can monitor if diet/lifestyle modifications in Type II are effective
7
Q
What are the diagnostic criteria that define diabetes?
A
- Fasting venous plasma glucose of >7mmol/L
- Random venous plasma glucose of >11.1mmol/L
- HbA1c of >6.5%
8
Q
Why can HbA1c NOT be used to diagnose Type I diabetes?
A
Patients have a short history of symptoms (onset is about 2-3 weeks)
9
Q
What defines Type I diabetes mellitus?
A
- Autoimmune destruction of β cells in islets of pancreas so no insulin production
- Insulin deficiency
- Hyperglycaemia
- Lipolysis leads to increased production of ketone bodies which can cause KETOACIDOSIS (fatal)
10
Q
Explain why Type II diabetes can be as a result of insulin resistance AND insulin deficiency
A
- Insulin resistance of cells means glucose cannot be utilised so plasma levels rise
- β cells secrete more insulin to compensate for high blood glucose
- Eventually β cells wear out (exhaustion) which leads to relative lack of insulin
- Type II diabetics can also require the administration of insulin
11
Q
List 3 factors (other than β cell failure) that can contribute to the cause of diabetes
A
- Drug induced e.g. Steroids
- Genetic defects of β cell or insulin action
- Pancreatitis (acute or chronic)
12
Q
Explain the presentation of Type I diabetes in a patient
A
- Patient usually
13
Q
Describe the effects of insulin on cell metabolism
A
- PROMOTES glycogenesis, lipogenesis, protein synthesis
- INHIBITS glycogenolysis, lipolysis, proteolysis, gluconeogenesis
14
Q
Explain how insulin deficiency can lead to weight loss and ketoacidosis
A
- Absolute lack of insulin so cells cannot utilise glucose
- Signals stress response so lipolysis is activated to produce ketone bodies for brain metabolism (as glucose is unable to enter)
- Fat metabolised so patient loses weight
- Ketone bodies can accumulate in blood altering the buffering mechanisms and causes ketoacidosis - fatal
15
Q
What factors can diagnose Type I diabetes straight away?
A
- Elevated venous plasma glucose >10mmol/L
- Presence of KETONES (smell acetone on breath)
- High blood pressure
- Family history
16
Q
How is Type I diabetes treated?
A
- Exogenous insulin injections (MUST)
- Subcutaneous insulin injections several times per day
- Fluids (saline, water)
17
Q
What percentage of people with Type II overweight or obese?
A
90%
18
Q
Describe the aetiology of Type II diabetes
A
- Insulin resistance due to obesity
- β cell failure which leads to relative lack of insulin
- Genetic and environmental factors
19
Q
Describe how obesity can lead to insulin deficiency
A
- First leads to insulin resistance
- Secretion of more insulin due to increase in circulating fatty acids (need to be stored)
- Pancreatic exhaustion
- Hyperglycaemia causes pancreas to secrete more insulin
- Eventually β cell failure occurs
- Can also have amyloid type deposits in islets which leads to β cell failure
20
Q
Explain why diet modification is the primary treatment method for Type II diabetes
A
- Has been shown to drastically reduce blood glucose within a short period of time
- Coupled with moderate exercise this is very effective
- If diet changes and exercise do not work, drugs can be administered
21
Q
What are the effects of a hypo-calorific diet on insulin resistance?
A
- Under hypo-calorific conditions fat is metabolised first from the LIVER (followed by other ectopic and subcutaneous sites)
- Decrease in fat around liver results in normal hepatic insulin sensitivity
- Glucose can slowly be utilised more so fasting glucose levels decrease
22
Q
Explain why a patient presenting with Type II diabetes may not have a presence of ketones
A
- Still producing some insulin
- Fatty acid oxidation is inhibited by insulin so no ketones produced
23
Q
Describe the presentation of a patient with Type II diabetes
A
- Most are >40 yrs however increasing in younger population
- Variable and slower rise in blood glucose
- Polyuria, Polydipsia, weight loss, lack of energy, persistent infections, blurred vision
- NO KETONES
- May be ASYMPTOMATIC
24
Q
What happens if Type I diabetes is left untreated?
A
- Severe hyperglycaemia
- KETOACIDOSIS
- Coma/DEATH
25
What happens if Type II diabetes is left untreated?
- Gradual worsening of symptoms e.g. Inadequate energy utilisation leading to sedentary behaviour
- Onset or worsening of complications related to diabetes e.g. Severe morbidity, mortality, susceptibility to CVDs
26
Explain the treatment methods of Type II diabetes
- PRIMARY treatment includes diet modification (low kcal) and moderate exercise
- If hyperglycaemia persists, can use drugs such as biguanides (Metformin), sulphonylureas and INSULIN
- Requires patient education for monitoring blood glucose
27
Describe the action of sulphonylureas
- Increase insulin release from (remaining) β cells
| - Reduce insulin resistance
28
Explain how the autoimmune destruction of β cells can be triggered
- Genetic predisposition associated with genetic markers HLA DR3 and HLA DR4
- Environmental trigger e.g. Viral infection that triggers immune response (activation of T lymphocytes and macrophages)
29
Explain how increased plasma glucose can lead to Polyuria and Polydipsia
- Glucose normally reabsorbed in PCT after ultrafiltration in glomerulus
- Reabsorption is ISOSMOTIC (same osmotic pressure)
- Increased plasma glucose filtered out is not all absorbed so some glucose remains in nephron - EXTRA OSMOTIC LOAD
- Less water reabsorbed to maintain isosmotic character so extra water is excreted along with glucose
- Leads to increased thirst as DEHYDRATION occurs
30
Explain why people with hyperglycaemia are more susceptible to urogenital and thrush infections
- Increased glucose concentration attracts bacteria
| - Growth environment for broth turbidity/Biofilms
31
Describe the presentation of a patient with KETOACIDOSIS
- Severely ill
- Hyperventilation (KUSSMAUL BREATHING)
- Prostration (elevated chest and abdomen)
- Nausea/vomiting
- Dehydration
- Abdominal pain
32
Describe how you could test for the presence of ketones
- Presence in urine using a KETOSTIK
| - Smell of acetone on breath
33
Explain why a person with diabetes may have blurred vision
- Hyperglycaemic
| - Increased plasma glucose causes lens of eye to swell, affecting the refractive index of the eye
34
Describe the steps of an oral glucose tolerance test
- Take fasting blood sample from patient
- Administer 75g glucose orally e.g. 395ml Lucozade
- Take another sample of blood after 2 hrs of administration
- If plasma glucose is >11.1mmol/L indicates hyperglycaemia
35
Explain how persistent hyperglycaemia may leave some tissues susceptible to ROS damage
- Uptake of glucose in some tissues is regulated by extracellular concentration e.g. Peripheral nerves, eye and kidney
- If plasma glucose is high, it leads to increased intracellular concentration
- Excess glucose metabolised by ALDOSE REDUCTASE into SORBITOL
- NADPH ---> NADP+ in the process
- Depletion of NADPH stores leaves cells more susceptible to oxidative damage as it is needed to recycle glutathione
36
How does GLYCATION differ from GLYCOSYLATION?
GLYCATION is non-enzymatic
37
Describe how glycation can affect protein function
- Glucose binds to free amino acid residues on proteins
| - Change in overall NET CHARGE and 3D structure of protein so disrupts functioning
38
What is diabetes mellitus?
- Blood glucose is too high (HYPERGLYCAEMIA) due to either absolute lack of insulin or decrease in cell sensitivity to insulin
- Can lead to problems such as ketoacidosis and micro/macrovascular damage
- Can cause premature death from CVD
39
Explain the significance of the HbA1c test
- GLYCATION of Haemoglobin in blood at terminal valine due to elevated blood glucose
- RBC have a lifespan of ~120 days
- Related to the average blood glucose over the preceding 120 days from when it was taken
- Can indicate how well blood glucose has been monitored in diabetics
40
List 3 MICROVASCULAR complications associated with diabetes
- Diabetic retinopathy
- Diabetic neuropathy
- Diabetic nephropathy
41
Explain why it is essential that the feet of diabetics are checked regularly
- Feet particularly vulnerable in diabetics
- Poor circulation
- Damage to nerves
- Increased risk of infection
- Failure to examine feet and detect changes may result in amputation (e.g. Gangrene)
42
What visual problems may be associated with diabetes?
- Glaucoma -> osmotic effects of glucose draw water into eye
- Cataracts -> production of sorbitol depletes NADPH stores which is needed for protection from ROS damage
- Retinopathy - damage to blood vessels (may rupture causing bleed; leakage leads to formation of protein exudates on retina)
- All can lead to BLINDNESS
43
Describe the cause and detection of diabetic nephropathy
- Damage to glomeruli due to high blood glucose
- Damage from infection of urinary tract
- Detected by increased amount of proteins such as ALBUMIN in urine
44
Explain how diabetic neuropathy can affect the feet of diabetics
- Damage to periphery nerves by increased intracellular concentration of glucose
- Depletion of NADPH stores, production of SORBITOL (causes osmotic damage to cells)
- Leads to loss of sensation and changes due to alteration of autonomic nervous system
- Damage to feet may go undetected
45
Explain how sorbitol is produced and what it's effects on the tissue is
- In some cells glucose uptake is determined by extracellular concentration
- In patients with hyperglycaemia the intracellular concentration of glucose increases (due to increased uptake) so glucose is converted to SORBITOL using aldose reductase
- Sorbitol causes OSMOTIC DAMAGE to cells and tissues
46
What are the MACROVASCULAR complications of diabetes?
- Increased risk of STROKE
- Increased risk of MYOCARDIAL INFARCTION
- Poor circulation to periphery - particularly in feet
