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Year 2 - BRS > 3.15 - Type 1 diabetes > Flashcards

3.15 - Type 1 diabetes Flashcards

1
Q

What is type 1 diabetes?

A
  • autoimmune condition in which insulin-producing beta cells in the pancreas are attacked and destroyed by the immune system
  • the result is a partial or complete deficiency of insulin production, which results in hyperglycaemia
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2
Q

What does the hyperglycaemia caused by T1DM require to treat?

A

Life-long insulin treatment

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3
Q

What is a flowchart of T1DM like?

A

environmental trigger / genetic risk –> autoimmune destruction of islets –> absolute insulin deficiency –> hyperglycaemia

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4
Q

What is a flowchart of T2DM like?

A

obesity / genetic risk –> insulin resistance –> relative insulin deficiency –> hyperglycaemia

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5
Q

What is the overlap between T1DM and T2DM presentation?

A
  • T1DM usually presents at a younger age, but autoimmune diabetes leading to insulin deficiency can present later in life - latent autoimmune diabetes in adults (LADA)
  • T2DM may present in childhood
  • diabetic ketoacidosis can be a feature of T2DM (usually feature of T1DM)
  • monogenic diabetes can present phenotypically as T1DM or T2DM (e.g. MODY, mitochondrial diabetes)
  • diabetes may present following pancreatic damage or other endocrine disease
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6
Q

Why is the fact that T1DM can develop in adults important?

A
  • traditionally thought to be a condition of childhood/early adulthood
  • now good evidence that it can present throughout every decade of life
  • clinicians are faced with a challenge of trying to differentiate adult-onset T1DM from the much larger number of cases of T2DM
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7
Q

Describe the graph showing the stages of development of T1DM?

A
  • early gestation - beta cell mass increases
  • after birth, beta cell mass is fixed
  • some people have a genetic predisposition
  • a potentially precipitating event happens (e.g. viral illness), causing beta cell mass to decline
  • there is initially an asymptomatic phase (cannot tell you are developing T1DM):
  • overt immunological abnormalities; normal insulin release
  • progressive loss of insulin release; glucose normal
  • overt diabetes; C-peptide (insulin) present
  • last stage, no C-peptide (insulin) present
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8
Q

What molecule do we use to measure insulin?

A

C-peptide (proinsulin made by beta cell –> insulin + C-peptide)

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9
Q

Why do we measure C-peptide instead of insulin (T1DM)?

A
  • easier to measure as insulin has short half life and undergoes hepatic first pass metabolism
  • also patients are on insulin anyway so you would not be able to tell how much insulin from injection and how much from pancreas
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10
Q

What are the stages of the immune response in T1DM?

A
  • genetic risk (15x increased risk in those with relatives)
  • immune activation - beta cells attacked
  • immune response - development of single autoantibody
  • stage 1: normal blood sugar, >2 autoantibodies
  • stage 2: abnormal blood sugar, >2 autoantibodies
  • stage 3: clinical diagnosis, >2 autoantibodies
  • stage 4: long-standing T1D, no autoantibodies
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11
Q

Why does the immune response stop in long-standing T1DM?

A

Immune attack stops/reduced as all beta cells are destroyed –> quiescent stage (no infiltration of immune cells into islet) = seronegativity

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12
Q

Why is the immune basis of T1DM important?

A
  • increased prevalence of other autoimmune disease too
  • risk of autoimmunity in relatives
  • more complete destruction of beta cells
  • autoantibodies can be useful clinically
  • immune modulation offers the possibility of novel treatments (not there yet)
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13
Q

Is there a defect in the innate or adaptive immune response in T1DM?

A

Defect in both innate and adaptive response

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14
Q

What is the mechanism of the autoimmune destruction of beta cells in T1DM?

A
  • first step is presentation of auto-antigen on beta cells to autoreactive CD4+ T lymphocytes
  • CD4+ cells activate CD8+ T lymphocytes
  • CD8+ cells travel to islets and lyse beta cells expressing auto-antigen
  • exacerbated by release of pro-inflammatory cytokines
  • underpinned also by defects in regulatory T cells that fail to suppress autoimmunity

Stained image shows infiltration of immune cells into islet

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15
Q

Are all beta cells destroyed in T1DM?

A
  • not necessarily - some people with T1DM continue to produce small amounts of insulin (these patients have fewer complications)
  • not enough to negate the need for insulin therapy
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16
Q

What gene (and allele) mediates genetic susceptibility to T1DM?

A

HLA-DR allele (HLA = human leukocyte antigen)

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17
Q

Is T1DM polygenic or monogenic?

A

Polygenic

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18
Q

What environmental factors are there that affect T1DM?

A

Multiple factors implicated but causality not been established:

  • enteroviral infections
  • cow’s milk protein exposure
  • seasonal variation
  • changes in microbiota
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19
Q

What are pancreatic auto-antibodies?

A
  • detectable in the sera of people with T1DM at diagnosis
  • now recommended for diagnosis in NICE guidelines:
    • insulin autoantibodies (IAA)
    • glutamic acid decarboxylase (GAD-65) - widespread neurotransmitter
    • insulinoma-associated-2 autoantibodies (IA-2)
    • zinc-transporter 8 (ZnT8)
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20
Q

What are the symptoms of T1DM? (7)

A
  • polyuria (excessive urination)
  • nocturia
  • polydipsia (excessive thirst)
  • blurring of vision
  • recurrent infections e.g. thrush
  • weight loss
  • fatigue
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21
Q

What are the signs of T1DM? (6)

A
  • dehydration
  • cachexia (extreme weight loss and muscle wasting)
  • hyperventilation
  • smell of ketones
  • glycosuria
  • ketonuria
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22
Q

What is the diagnosis of T1DM based on?

A
  • clinical features and presence of ketones
  • in some cases pancreatic autoantibodies/C-peptide may be measured
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23
Q

What does a lack of insulin do to the body?

A
  • proteinolysis of muscles –> AAs
  • increased HGO from liver
  • lipolysis of fat cells into glycerol and NEFA
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24
Q

What happens to the NEFAs in the liver?

In the absence of insulin, fat cells undergo lipolysis –> NEFA + glycerol

A

Undergo oxidation to produce three species: acetyl CoA, acetoacetate, acetone + 3 OH-B - these are ketone bodies which build up and cause ketoacidosis (acidic blood if left untreated)

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25
Q

What do people with T1DM require?

A

Insulin for life

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26
Q

What are the aims of treatment in T1DM?

A
  • maintain glucose levels without excessive hypoglycaemia
  • restore a close to physiological insulin profile
  • prevent acute metabolic decompensation (DKA)
  • prevent microvascular and macrovascular complications
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27
Q

What is an acute complication of hyperglycaemia?

A

Diabetic ketoacidosis

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28
Q

What are the chronic microvascular complications of hyperglycaemia? (3)

A
  • retinopathy (blood vessels in eye)
  • neuropathy (nerves in feet)
  • nephropathy (kidneys)
29
Q

What are the chronic macrovascular complications of hyperglycaemia? (3)

A
  • ischaemic heart disease
  • cerebrovascular disease (stroke)
  • peripheral vascular disease
30
Q

What is a complication of the insulin treatment itself (iatrogenic) in T1DM?

A

Hypoglycaemia

31
Q

How do we manage T1DM?

A
  • insulin treatment
  • dietary support/structured education
  • technology e.g. pump
  • transplantation (pancreas / islet cell)
  • T1DM is a ‘self-managed’ condition
32
Q

What does a physiological insulin profile in a normal person look like?

A
  • plasma insulin level peaks at every meal
  • prandial peak has two phases - one main splurge of insulin, another later on to clean up any left over glucose
  • basal insulin has a flat profile
  • insulin is never completely suppressed
33
Q

Why is insulin never completely suppressed in a physiological insulin profile?

A

You start forming ketones, breaking down fat and muscle –> DKA –> death

34
Q

What are the two types of insulin given to patients?

A
  • with meals (short/quick-acting/bolus insulin)
  • background (long-acting/basal insulin)
35
Q

What are examples of short/quick-acting insulin?

A
  • human insulin - exact molecular replicate of human insulin (actrapid)
  • insulin analogue (Lispro, Aspart, Glulisine)
36
Q

What are examples of long-acting/basal insulin?

A
  • bound to zinc or protamine (Neutral Protamine Hagedorn, NPH)
  • insulin analogue (Glargine, Determir, Degludec)
37
Q

How does the basal-bolus insulin regime work?

A
  • patient wakes up and takes long-acting insulin
  • they take short-acting insulin three times a day with meals
38
Q

What is another option of the basal-bolus insulin regime?

A
  • actrapid three times a day with meals
  • twice daily intermediate acting insulin
39
Q

What are we not able to master with the basal-bolus regime?

A

We are trying to replicate the physiological insulin profile of a normal person but have not mastered the basal flat level or the dual prandial peaks

40
Q

What does insulin pump therapy do?

A
  • continuous delivery of short-acting insulin analogue e.g. novorapid via pump
  • delivery of insulin into subcutaneous space
  • programme the device to deliver fixed units across the hour of every day
  • actively bolus for meals
41
Q

What are the advantages of insulin pump therapy? (3)

A
  • variable basal rates
  • extended boluses
  • greater flexibility
42
Q

What do NICE guidelines say about dietary advice to those with T1DM?

A

All people with T1DM should be offered a Structural Education Programme e.g. DAFNE (dose adjustment for normal eating) - 5 day course on skills and training in self-management

43
Q

What are the principles of dietary advice for those with T1DM?

A
  • dose adjustment for carbohydrate content of food
  • all people with T1DM should receive training for carb counting
  • where possible, substitute refined carb containing foods (sugary/high glycaemic index) with complex carbs (starchy/low glycaemic index)
44
Q

What is a closed loop system/artificial pancreas?

A
  • real-time continuous glucose sensor detects a change in glucose
  • algorithm to use glucose value to calculate insulin requirement
  • insulin pump delivers calculated insulin
  • available on NHS
45
Q

What are the two types of transplantation for T1DM management?

A
  • islet cell transplant
  • simultaneous pancreas and kidney transplants
46
Q

What happens in an islet cell transplant?

A
  • isolate human islets from pancreas of deceased donor
  • transplant into hepatic portal vein
47
Q

What is the advantage of doing a simultaneous pancreas and kidney transplant?

A

Better survival of pancreas graft when transplanted with kidneys

48
Q

What do both transplantation methods require?

A

Life-long immunosuppression

49
Q

What is the aim of transplantation methods to manage T1DM?

A
  • try and restore physiological insulin production to the extent that insulin can be stopped
  • even if incomplete, often results in better control
50
Q

What are the limitations of transplantation? (3)

A
  • availability of donors
  • complications of life-long immunosuppression
  • some fail = back to insulin supplements
51
Q

How do we monitor glucose levels? (2)

A
  • capillary (finger prick) blood glucose monitoring
  • continuous glucose monitoring (restricted availability, NICE guidelines)
52
Q

What does glycated haemoglobin (HbA1c) show?

A
  • reflects last 3 months (RBC lifespan) of glycaemia
  • biased to the 30 days preceding measurement
  • glycated not glycosylated (enzymatic)
  • therefore linear relationship between how much glucose we have and how high HbA1c is
  • irreversible reaction
53
Q

What happens biologically to show relationship between BGC and HbA1c?

A
  • when Hb comes into contact with glucose, glucose joins to N-terminal valine residue in beta chain
  • produces a Schiff base (fast hrs, reversible)
  • after time this produces an Amadori product (HbA1c) - slow, days
  • irreversible
54
Q

When is HbA1c not perfect?

A

When certain things affect RBC turnover:

  • erythropoiesis
  • altered Hb
  • glycation
  • erythrocyte destruction
55
Q

What is used to guide insulin doses?

A
  • use self-monitoring of blood glucose results at home and HbA1c results every 3-4 months
  • based on results, increase or decrease doses
56
Q

What are the acute complications from T1DM? (3)

A
  • diabetic ketoacidosis
  • uncontrolled hyperglycaemia
  • hypoglycaemia
57
Q

When can diabetic ketoacidosis present?

A
  • can be a presenting feature of new-onset T1DM
  • occurs in those with established T1DM (indicates acute illness, missed/inadequate insulin doses esp long-acting)
  • can occur in any type of diabetes
  • life-threatening complication

Treatment: IV fluids 0.9% NaCl –> insulin infusion +/- K+ supplementation

58
Q

How do we diagnose diabetic ketoacidosis?

A
  • pH <7.3
  • ketones increased (urine/capillary blood)
  • HCO3- <15mmol/L
  • glucose >11mmol/L
59
Q

What is the case with hypoglycaemia with T1DM?

A
  • to some extent an inevitable feature of the self-management of T1DM
  • may become debilitating with increased frequency
  • numerical definition is <3.6 mmol/L
60
Q

What is severe hypoglycaemia?

A

Any event requiring third party assistance

61
Q

What are the adrenergic symptoms of hypoglycaemia? (4)

A
  • tremors
  • palpitations
  • sweating
  • hunger
62
Q

What are the neuroglycopenic symptoms of hypoglycaemia? (4)

A
  • somnolence (drowsy)
  • confusion
  • incoordination
  • seizures, coma
63
Q

When does hypoglycaemia become a problem? (4)

A
  • excessive frequency
  • recurrent severe hypoglycaemia
  • nocturnal hypoglycaemia
  • impaired awareness (unable to detect low blood glucose)
64
Q

What are the risks of hypoglycaemia? (5)

A
  • seizure / coma / death
  • impact on emotional wellbeing
  • impacts on driving
  • impacts on day to day function
  • impacts on cognition
65
Q

Is HbA1c useful at identifying hypoglycaemia?

A

HbA1c itself may not be useful in identifying hypoglycaemia since it looks at last 3 months altogether

66
Q

What are risk factors for T1DM people for hypoglycaemia? (6)

A
  • exercise
  • missed meals
  • lack of training around dose-adjustment for meals
  • inappropriate insulin regime
  • alcohol intake
  • lower HbA1c
67
Q

What are strategies to support problematic hypoglycaemia? (5)

A
  • indication for insulin pump therapy (CSII)
  • try different insulin analogues
  • transplantation
  • revisit carb counting/structured education
  • behavioural psychology support
68
Q

What is the acute management of hypoglycaemia?

A
  • if alert and oriented - oral carbs; rapid acting (juice/sweets); longer acting (e.g. sandwich)
  • if drowsy/confused but swallow intact - buccal glucose e.g. Hypostop/glucogel; complex carb
  • unconscious/concerned about swallow - IV access; 20% glucose IV
  • deteriorating/refractory/insulin-induced/difficult IV access: consider IM/SC 1mg glucagon
69
Q

What is the language matters movement with T1DM?

A

Use language that empowers people with T1DM rather than disengage them

Phrases to avoid:

  • poor control
  • not coping
  • how’s your control
  • they’re diabetic
  • you can’t eat that
  • diabetes sufferer
  • poor compliance

Empowering language:

  • person living with diabetes
  • sounds like your diabetes has been challenging to manage recently
  • what are your thoughts on your recent glucose levels
  • let’s talk through different options and see what suits you

Year 2 - BRS (84 decks)

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