Type 1 Diabetes Flashcards
What is type 1 diabetes?
Autoimmune disease. There is a loss of self-tolerance which means T-cell target the beta cell antigens.
What are the genes that cause the inappropriate immune response?
HLA DR3 and HLA DR4
What normally happens in the pancreatic beta cell?
- Glucose enter via glucose transporter
- Glucose undergoes anaerobic and aerobic metabolism to produce ATP.
- ATP bind to potassium sensitive channels, causing them to close.
- Potassioum builds up in beta cells, making it positively changed, activating voltage gated calcium channels.
- Calcium enters and stimulates vesicle that contain insulin.
What does GAD enzyme do in the pancreatic beat cells?
Converts glutamic acid into GABA. GABA is associated with insulin production and protective effects of beta cells.
3 parts that antibodies attack in pancreatic beta cells
- Specific self-antigens on pancreatic islet cells.
- GAD enzyme
- Insulin
What are the high yield antibodies that attack the islet cells antigens?
Anti-islet cell antibodies
What are the high yield antibodies that attack the GAD enzyme?
Anti-GAD antibodies
What are the antibodies that attack the insulin?
Anti-insulin antibodies
What do the antibodies do to pancreatic beta cell?
- Attack the 3 parts of the beat cells
- Destrpy beta cells. (less beta cells)
- Reduces insulin production
- Incerease blood glucose
What does insulin do to glucose normally?
- Insluin binds to insulin receptors
- Increaes expression of glucose transporters
- Glucose enters cell reducing blood glucose levels.
Thirst
- Blood volume drops as increased water and glucose lost in urine
- Gluose high and water low in the blood
- This stimulates osmoreceptors in the hypothalamus
- This triggers increased thirst
What is high glucose and low water in the blood?
Hyperosmolar blood
What is increased thirst?
Polydipsia
What causes increased glucose in the urine?
- Alot of glucose filtered into kidneys via the glomerulus filtrate
- Too much glucose to be able to be reabsorbed via the kidney tubules
- More glucose in the urine
What does more glucose in the urine do?
- Glucose osmotically active
- Pull water with it
- So lose more water via urine
Why does diabetes cause increased urine (Going to the Toilet more often)?
- Too much glucose to be able to be reabsorbed via the kidney tubule so more glucose in the urine
- Glucose osmotically active, pulls water with it
- So lose more water via urine
What is increased glucose in the urine?
Glycosuria
What is increased urine?
Polyurea
Thinner
- Decaraed glucose in cells = decreased ATP
- Uses fat and muscles for fuel, lipolysis and proteolysis
- The breakdown of fat and protein causes unexplained weight loss.
- This can also increase hunger.
4 Ts of type 1 diabetes
Toilet, Thirsty, Tired and Thinner
What does decreased glucose in cells do to ATP?
Decreased ATP
What is lipolysis?
Breakdown of triglycerides into free fatty acids and glycerol. This can be used to make ATP.
What is proteolysis?
Breakdown of protein in muscles to amino acids. This is used to make ATP.
What is polyphagia?
Increased hunger
Fasting glucose for diagnosis?
> 126mg/dl
Random glucose for diagnosis?
> 200 mg/dl
2 hour oral GGT for diagnosis?
> 200 mg/dl on 2 tests
HbA1c for diagnosis?
> 6.5%
What is a 2 hour glucose tolerance test?
Glucose given, and gluose remains high.
What is HbA1c?
Gluose in the blood likes to conjugate to the Hb, this makes a glycated Hb (Hgb). So it is a measurement of Hgb.
Over what time does the HbA1c help monitor blood glucose?
3 months as that is the life span of RBC.
Treatment for Type 1 diabetes?
Insulin to reduce blood glucose.
DKA
Ketone bodies increase acid in the blood
DKA symptoms
- Heavy breathing
- Hyperkalemia
- Sweet smell from breath
Why does DKA cause heavy breathing?
Body wants to reduce CO2 to reduce acidity.
DKA treatment
Fluids for dehydration
Insulin to lower blood glucose
Electrolytes (K+)
Types of insulin (8)
- Ultra Rapid Acting
- Rapid acting.
- Short acting.
- Intermediate acting.
- Long acting.
- Ultra long acting
- Human mixed insulins.
- Analogue mixed insulins.
Ultra Rapid Acting: When to take
Just before, with or up 20 mins after food
Rapid acting: When to take
Just before, with or just after food
Short acting: When to take
30 mins before food
Intermediate acting: When to take
30 mins before food or bedtime
Long acting: When to take
Once or twice a day
Ultra long acting: When to take
Once a day
Human mixed insulins: When to take
30 mins before meal
Analogue mixed insulins: When to take
Just before, with or just after food
Ultra Rapid Acting: Onset, Peak, duration
Onset: 2-3 mins
Peak: 30-90 mins
Duration: 5 hours
Rapid acting: Onset, Peak, duration
Onset: 10-20 mins
Peak: 1-3 hours
Duration: 2-5 hours
Short acting: Onset, Peak, duration
Onset: 30-60 mins
Peak: 1-5 hours
Duration: 5-9 hours
Intermediate acting: Onset, Peak, duration
Onset: 60-90 mins
Peak: 2-12 hours
Duration: 12-24 hours
Long acting: Onset, Peak, duration
Onset: 2-4 hours
Peak: No peak 6-14 hours
Duration: 20-24 hours (16-20 hours Levemir)
Ultra long acting toujeo: Onset, Peak, duration
Onset: 6 hours
Peak: no peak
Duration: 36 hours
Ultra long acting tresbia: Onset, Peak, duration
Onset: 30-90 mins
Peak: no peak
Duration: over 42 hours
Human mixed insulins: Onset, Peak, duration
Onset: 30 mins
Peak: 1- 4 hours
Duration: 12-24 hours
Analogue mixed insulins: Onset, Peak, duration
Onset: 10-20 mins
Peak: 1-4 hours
Duration: 24 hours
Dose Depends on
- Age
- Exercise
- Physical activity
- Stress
- Hormonal changes
Ultra Rapid Acting: When to use
Forgetful or regular does not eat whole meal.
It can be taken after so can be tailored to what they have consumed, or if they have forgotten to take before.
Rapid acting: When to use
Forgetful or regular does not eat whole meal.
It can be taken after so can be tailored to what they have consumed, or if they have forgotten to take before.
Short acting: When to use?
Usually avoided as they need to be taken 30 mins before. So people may forget/get distracted and go into hypo.
Human mixed insulins and Analogue mixed insulins: When to use
Not really for type one, as you need variability. For people who do not have much variability.
Ultra Rapid Acting: Basal or bolus
Bolus
Rapid acting: Basal or bolus
Bolus
Short acting: Basal or bolus
Bolus
Intermediate acting: Basal or bolus
Basal
Long acting: Basal or bolus
Basal
Ultra long acting: Basal or bolus
Basal
Human mixed insulins
Intermediate acting and short acting
Analogue mixed insulins
Rapid acting and intermediate acting
Basal vs bolus
Background insulin vs meal time insulin
Dose considerations: Age
Older people usually require lower dose
Older more likely go into hypo overnight
Hypo more likely causes arrythmias in older people
Pathogenesis of type 1
Beta cell of pancreas destroyed by cytotoxic CD8-T cells reactive against peptides of insulin and of other specific proteins which are complexed with MHC molecules and recognized by cytotoxic T lymphocytes (CLT)
What are the effects of the lack of insulin in type 1 diabetes? (4)
- Tissues cannot accumulate and store glucose
- Tissues cannot use glucose as metabolic fuel
- Body cannot store excess energy as fat
- Reduced synthesis of protein
Dehydration, excessive urine production and thirst mechanism (6)
- High [Glucose] enters glomerular filtrate and overwhelms glucose absorbing capacity of proximal convoluted tubule
- Increased fluid osmolarity in tubules
- More water is secreted from cells into the proximal convoluted tubule
- causes increased urine flow –diuresis
- Water reabsorption is reduced
- Dehydration, excessive urine production and thirst
What happens when the same injecting is overused?
Cells close to site of insulin injection exposed to high [insulin]
If same site used again and again will promote deposition of fat around injection site (lipohypertrophy)
Why is changing injection site clinically important
As leads to unpredictable rate of insulin absorption. This could lead to poor glycaemic control and patients could experience hyper/hypoglycaemic events.
First choice treatment for type 1
- Multiple daily injection basal-bolus insulin regimens
- One or more separate daily injections of intermediate/long acting insulin analogue
- Multiple injections of short acting forms before meals
Alternative treatments for type 1 (3)
- 1-2-3 injections per day of a short acting form mixed with intermediate acting form
- Insulin pump (A regular amount of rapid insulin delivered via a programmable pump via a subcutaneous cannula). Only used for patients suffering from severe hypoglycemia and/or high Glycosylated haemoglobin (69mmol and above)
Teplizumab
Monoclonal antibody that targets the compotnet of the