Type 1 Diabetes Mellitus Flashcards
What is type 1 diabetes?
- autoimmune condition where insulin-producing beta-cells in the pancreas are destroyed by the immune system
- result is partial or complete insulin deficiency > hyperglycaemia
What classifies type 1 diabetes?
autoimmune destruction of islets > absolute insulin deficiency
What is latent autoimmune diabetes in adults (LADA)?
autoimmune diabetes leading to insulin deficiency presents later in life
Why is the autoimmune basis of type 1 diabetes important?
- increased prevalence of other autoimmune diseases
- increased complete destruction of beta-cell
Which HLA-DR alleles increase the risk of diabetes significantly?
DR3, DR4
What are the possible environmental factors in developing type 1 diabetes?
NO causation relationship
- enteroviral infections (koksaki virus)
- cow’s milk protein exposure
- seasonal variation
- changes in microbiota
Key characteristic of type 1 diabetes?
Ketones in urine
What is needed to stop ketonegenesis?
Insulin
Basal bolus insulin regimen
What can be a trigger for DM?
- pancreatic damage
- endocrine disease
What is MODY?
when there is a single genetic defect that has caused the development of diabetes
When can T1DM develop?
at any decade of life
How does T1DM develop?
- genetic predisposition
- precipitating event
- asymptomatic beta cell decline
- no C-peptide present
What do you use to measure insulin production in T1DM?
C-peptide
What produces C-pepetide?
the conversion of pro insulin (from beta cells) to insulin - cleavage product
Why do we measure C-peptide?
people with T1DM will be taking insulin and therefore will have normal levels if insulin is measured
What happens after the precipitating event?
- immune activation leads to beta cell attack
- development of single autoantibodies
What can be seen on microscope in islet cells?
- immune cells concentrated in islet cell
- after attack, much lower numbers of immune cells
Why is the immune aspect important?
- increased risk of other autoimmune diseases
- complete destruction of B-cells
- autoantibodies and immune modulation offer possible novel treatments
How long does the asymptomatic stage last?
dependent on how aggressive the immune response is (more steep in children, gradual in adults)
Why does the immune activation occur?
due to a defect in both the innate and adaptive immune system
What happens in immune activation?
- 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
Are all b-cells destroyed in the development in T1DM?
SOME produce small amounts of insulin therefore NO
BUT, insulin is still needed
What is the effect of the remaining insignificant insulin production?
fewer, less severe complications associated with T1DM
What are the symptoms associated with T1DM?
- polyuria
- nocturia
- polydipsia
- blurred vision
- recurrent infections (thrush)
- weight loss
- fatigue
(short duration)
When does ketoacidosis occur?
- low/no insulin
- acute insulin resistance due to counter-regulatory response (adrenalin…)
When are pancreatic autoantibodies are detected?
in the sera of people of T1DM
What are the pancreatic antibodies in response to proteins from b-cells?
- Insulin antibodies (IAA)
- Glutamic acid decarboxylase (GADA)
- Insulinoma-associated-2 autoantibodies (IA-2A) Zinc transporter 8 (ZnT8)
What are the signs of T1DM?
- dehydration
- cachexia
- hyperventilation
- smell of ketones (pear drop)
- glyosuria
- ketonuria
Why does blurred vision occur in T1DM?
high glucose levels cause osmotic shifts in the eyeball
What is the diagnosis of T1DM based on?
- clinical features
- presence of ketones
occasionally: - pancreatic autoantibodies
- C-peptide
What are the effects of insulin deficiency?
- proteinolysis (AA)
- hepatic glucose output
- lipolysis (NEFA + triglycerides)
What happens to NEFA’s?
oxidised in the liver to produce ketone bodies, which are acidic and can accumulate causing diabetic ketoacidosis
Which ketone bodies are involved in ketoacidosis?
- acetyl CoA
- acetoacetate
- acetone + 3 OH-B
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
Why does high glucose cause weight loss?
- osmotic diuresis
- dehydration
- no calorie retention
- muscle breakdown for energy
What does MODY stand for?
Maturity Onset Diabetes of the Young
What are the acute complications associated with T1DM?
diabetic ketoacidosis
What are the chronic microvascular complications associated with T1DM?
- retinopathy
- neuropathy
- nephropathy
What are the chronic macrovascular complications associated with T1DM?
- ischaemic heart disease
- cerebrovascular disease
- peripheral vascular disease
What are the complications associated with the treatment of T1DM?
hypoglycaemia
How do you manage T1DM?
SELF-MANAGED
- insulin treatment
- dietary support
- education
- technology
- transplantation
What are the 2 different types of insulin?
- short/quick-acting/with meals
- long-acting/basal/background
What is short/quick-acting insulin/with meals?
- human insulin (exact molecular replica)
- Insulin analogue (Lispro, Aspart, Glulisine)
What is long-acting/basal/background insulin?
- bound to Zn or protamine (neutral protamine hagedorn, NPH)
- Insulin analogue (Glargine, Dermitir, Degludec)
What is a typical basal bolus regime?
1) long acting (1 x daily - morning)
2) short acting
What cannot be replicated using basal bolus?
- basal profile between meals is not flat
- only one peak in the longacting phase of the insulin
What does an insulin pump do?
continuous delivery of short-acting insulin analogue into s/c space
What is the advantage of using an insulin pump?
- program insulin to deliver different amounts across the day
- variable basal rates
- extended boluses
- greater flexibility
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
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
What is a hybrid closed-loop system?
when eating, must intervene with pump especially when eating refined carbohydrates
What happens in islet cell transplants?
- isolate human islets from pancreas
- transplant into hepatic portal vein
- required life long immunosuppression
What happens in simultaneous pancreas and kidney transplants?
- better survival of pancreas graft when transplanted with kidneys
- requires life-long immunosuppression
What are the limitations of transplants?
- donor availability
- life-long immunosuppression complications
How can you monitor glucose levels?
- capillary (finger prick) blood glucose measurement
- continuous glucose monitoring
What does a HbA1c show?
- glycated haemoglobin (glucose+haemoglobin)
- irreversible reaction
- reflects last 3 months
- measured every 3-4months
What are the acute complications associated with T1DM?
- diabetic ketoacidosis
- uncontrolled hyperglycaemia
- hypoglycaemia
When does diabetic ketoacidosis occur in established T1DM?
- acute illness
- missed insulin doses
- inadequate insulin doses
How do you diagnose diabetic ketoacidosis?
- pH <7.3
- ketones increased (urine or blood)
- HCO3- <15mmol/L
- glucose >11mmol/L
What measurement is deemed as hypoglycaemia?
<3.6mmol/L (variable 3.5-4)
What is the effect of frequent (too many) hypoglycaemia?
- exhaustion
- confusion
- tremors
- palpitations
- sweating
- hunger
- somnolence
- inco-ordination
- seizures
- coma
How many hypoglycaemic episodes is normal?
2/week
What quantifies severe hypoglycaemia?
an episode that requires 3rd party help
When does hypoglycaemia become a problem?
- excessive frequency
- impaired awareness (unable to detect low blood sugar)
- nocturnal hypoglycaemia
- recurrent severe hypoglycaemia
What are the risks of hypoglycaemia?
- seizure/coma/death
- emotional impact
- impair driving
- impaired day-to-day function
- cognition impacts
What is not useful to identify a hypoglycaemic episode?
HbA1c
What increases the risk of hypoglycaemia?
- exercise
- missed meals
- inappropriate insulin regime
- alcohol intake
- low HbA1c
- lack of training on dose adjustment
What can be done to support problematic hypoglycaemia?
- insulin-pump therapy
- different insulin analogues
- revisit carbohydrate counting/education
- psychological support
- transplantation
