Type 1 Diabetes Mellitus Flashcards
1
Q
What is type 1 diabetes?
A
- autoimmune condition where insulin-producing beta-cells in the pancreas are destroyed by the immune system
- result is partial or complete insulin deficiency > hyperglycaemia
2
Q
What classifies type 1 diabetes?
A
autoimmune destruction of islets > absolute insulin deficiency
3
Q
What is latent autoimmune diabetes in adults (LADA)?
A
autoimmune diabetes leading to insulin deficiency presents later in life
4
Q
Why is the autoimmune basis of type 1 diabetes important?
A
- increased prevalence of other autoimmune diseases
- increased complete destruction of beta-cell
- Auto antibodies can be useful clinically
- Immune modulation offers the possibility of novel treatments
5
Q
Which HLA-DR alleles increase the risk of diabetes significantly?
A
DR3, DR4
6
Q
What are the possible environmental factors in developing type 1 diabetes?
A
NO causation relationship
- enteroviral infections (koksaki virus)
- cow’s milk protein exposure
- seasonal variation
- changes in microbiota
7
Q
Key characteristic of urine in type 1 diabetes?
A
Ketones in urine
8
Q
What is needed to stop ketogenesis?
A
Insulin
Basal bolus insulin regimen
9
Q
What can be a trigger for DM?
A
- pancreatic damage
- endocrine disease
10
Q
What is monogenic diabetes?
A
when there is a single genetic defect that has caused the development of diabetes e.g. MODY
11
Q
When can T1DM develop?
A
at any decade of life
12
Q
How does T1DM develop?
A
- genetic predisposition
- precipitating event
- asymptomatic beta cell decline
- no C-peptide present
13
Q
What do you use to measure insulin production in T1DM?
A
C-peptide
14
Q
What produces C-pepetide?
A
the cleavage of pro insulin (from beta cells) into insulin
15
Q
Why do we measure C-peptide?
A
people with T1DM will be taking insulin and therefore will have normal levels if insulin is measured
16
Q
What happens after the precipitating event?
A
- immune activation leads to beta cell attack
- development of single autoantibodies
17
Q
What can be seen on microscope in islet cells?
A
- immune cells concentrated in islet cell
- after attack, much lower numbers of immune cells
18
Q
How long does the asymptomatic stage last?
A
dependent on how aggressive the immune response is (faster in children, gradual in adults)
19
Q
Why does the immune activation occur?
A
due to a defect in both the innate and adaptive immune system
20
Q
What happens in immune activation?
A
- CD4+T lymphocytes identify autoantigen
- CD4+ cells activated CD8+ cells
- CD8+ travel to islets and lyse b-cells
- increased by pro-inflammatory cytokine release
- worsened by defects in regulatory T cells, failure to suppress autoimmunity
21
Q
Are all b-cells destroyed in the development in T1DM?
A
- SOME produce small amounts of insulin therefore NO
- BUT, insulin is still needed
22
Q
What is the effect of the remaining insignificant insulin production?
A
fewer, less severe complications associated with T1DM
23
Q
What are the symptoms associated with T1DM?
A
- polyuria
- nocturia
- polydipsia
- blurred vision
- recurrent infections (thrush)
- weight loss
- fatigue
(short duration)
24
Q
When does ketoacidosis occur?
A
- low/no insulin
- acute insulin resistance due to counter-regulatory response (adrenaline)
25
Where are pancreatic autoantibodies detected?
in the serum of people with T1DM
26
What are the pancreatic antibodies in response to proteins from b-cells?
- Insulin antibodies (IAA)
- Glutamic acid decarboxylase antibodies (GADA)
- Insulinoma-associated-2 autoantibodies (IA-2A)
- Zinc transporter 8 (ZnT8)
27
What are the clinical signs of T1DM?
- dehydration
- cachexia (muscle wasting)
- hyperventilation
- smell of ketones (pear drop)
- glycosuria
- ketonuria
28
Why does blurred vision occur in T1DM?
high glucose levels cause osmotic shifts in the eyeball
29
What is the diagnosis of T1DM based on?
- clinical features
- presence of ketones
occasionally
- pancreatic autoantibodies
- C-peptide
30
What are the effects of insulin deficiency?
- proteinolysis (AA)
- increased hepatic glucose output
- lipolysis (NEFA/free fatty acids + triglycerides)
31
What happens to NEFAs/free fatty acids?
oxidised in the liver to produce ketone bodies, which are acidic and can accumulate causing diabetic ketoacidosis
32
Which ketone bodies are involved in ketoacidosis?
- acetyl CoA
- acetoacetate
- acetone + 3 OH-B
33
What are the aims when treating T1DM?
- maintain glucose levels w/o hypo
- restore insulin profile
- prevent acute metabolic decompensation
- prevent micro and macrovascular complications
34
Why does high glucose cause weight loss?
- osmotic diuresis
- dehydration
- no calorie retention
- muscle breakdown for energy
35
What does MODY stand for?
Maturity Onset Diabetes of the Young
36
What are the acute complications associated with T1DM?
diabetic ketoacidosis
37
What are the chronic microvascular complications associated with T1DM?
- retinopathy
- neuropathy
- nephropathy
38
What are the chronic macrovascular complications associated with T1DM?
- ischaemic heart disease
- cerebrovascular disease
- peripheral vascular disease
39
What are the complications associated with the treatment of T1DM?
hypoglycaemia
40
How do you manage T1DM?
SELF-MANAGED
- insulin treatment
- dietary support
- education
- technology
- transplantation
41
What are the 2 different types of insulin?
- short/quick-acting/with meals
- long-acting/basal/background
42
What is short/quick-acting insulin/with meals?
- human insulin (exact molecular replica)
- Insulin analogue (Lispro, Aspart, Glulisine)
43
What is long-acting/basal/background insulin?
- bound to Zn or protamine (neutral protamine hagedorn, NPH)
- Insulin analogue (Glargine, Dermitir, Degludec)
44
What is a typical basal bolus regime?
1) short acting Actrapid (human insulin) 3 x daily
2) longacting once daily
45
What cannot be replicated using basal bolus?
- basal profile between meals is not flat
- only one peak in the longacting phase of the insulin
46
What does an insulin pump do?
continuous delivery of short-acting insulin analogue into subcutaneous space
47
What is the advantage of using an insulin pump?
- program insulin to deliver different amounts across the day
- variable basal rates
- actively bolus for meals
- greater flexibility
48
What is included in the structured education programs for T1DM?
- dose adjustment for carbohydrate content
- training on carbohydrate counting
- substitute refined carbohydrates for complex carbohydrates
49
What is involved in an artificial pancreas/closed-loop?
glucose monitor + insulin pump
- real time continuous glucose sensor
- calculate insulin requirement
- pump delivers the calculated insulin
50
What happens in islet cell transplants?
- isolate human islets from pancreas
- transplant into hepatic portal vein
- required life long immunosuppression
51
What happens in simultaneous pancreas and kidney transplants?
- better survival of pancreas graft when transplanted with kidneys
- requires life-long immunosuppression
52
What are the limitations of transplants?
- donor availability
- life-long immunosuppression complications
53
How can you monitor glucose levels?
- capillary (finger prick) blood glucose measurement
- continuous glucose monitoring
54
What does a HbA1c show?
- glycated haemoglobin (glucose+haemoglobin)
- irreversible reaction
- reflects last 3 months of glycaemia
- measured every 3-4months
55
What are the acute complications associated with T1DM?
- diabetic ketoacidosis
- uncontrolled hyperglycaemia
- hypoglycaemia
56
Which events can cause diabetic ketoacidosis in established T1DM?
- acute illness
- missed insulin doses
- inadequate insulin doses
57
How do you diagnose diabetic ketoacidosis?
- pH <7.3
- ketones increased (urine or blood)
- HCO3- <15mmol/L
- glucose >11mmol/L
58
What measurement is deemed as hypoglycaemia?
<3.6mmol/L (variable 3.5-4)
59
What is the effect of frequent (too many) hypoglycaemia?
- exhaustion
- confusion
- tremors
- palpitations
- sweating
- hunger
- somnolence
- inco-ordination
- seizures
- coma
60
How many hypoglycaemic episodes is normal?
2/week
61
What quantifies severe hypoglycaemia?
an episode that requires 3rd party help
62
When does hypoglycaemia become a problem?
- excessive frequency
- impaired awareness (unable to detect low blood sugar)
- nocturnal hypoglycaemia
- recurrent severe hypoglycaemia
63
What are the risks of hypoglycaemia?
- seizure/coma/death
- emotional impact
- impair driving
- impaired day-to-day function
- cognition impacts
64
What is not useful to identify a hypoglycaemic episode?
HbA1c
65
What increases the risk of hypoglycaemia?
- exercise
- missed meals
- inappropriate insulin regime
- alcohol intake
- low HbA1c
- lack of training on dose adjustment
66
What can be done to support problematic hypoglycaemia?
- insulin-pump therapy
- different insulin analogues
- revisit carbohydrate counting/education
- psychological support
- transplantation
67
What is the managment of hypoglycaemia in a person who is alert and orientated?
- oral carbohydrates
- juice or sweets
- sandwich
68
What is the acute managment of hypoglycaemia in a person who is drowsy/confused but can still swallow?
- buccal glucose
- glucogel
- complex carbohydrates
69
What is the acute managment of hypoglycaemia in a person who is unconscious or may not be able to swallow?
- IV access
- 20% IV glucose
