**_🧪Endocrinology🧪 - Type 1 Diabetes Mellitus Flashcards

1
Q

What is type 1 diabetes?

A

An autoimmune condition where insulin secreting beta-cells are attacked and destroyed

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2
Q

What are the consequences of T1DM?

A

Partial/complete insulin deficiency, leading to hyperglycaemia
Life-long insulin treatment

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3
Q

What is LADA?

A

Latent autoimmune diabetes in adults
Autoimmune diabetes leading to insulin deficiency can present later in life

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4
Q

What is diabetic ketoacidosis?

A

Cells (particularly hepatocytes) start making ketones as alternative fuel source due to lack of glucose (can’t enter from bloodstream), leads to ketoacidosis - acutely unwell patient
Usually sign of T1DM, but can also occur in T2DM

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5
Q

What is monogenic diabetes?

A

Some rare forms of diabetes result from mutations or changes in a single gene - called monogenic
Can present as T1/T2DM

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6
Q

What can trigger a presentation of diabetes?

A

Diabetes may present following pancreatic damage or another endocrine disease

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7
Q

What ages can T1DM present?

A

Usually childhood/early adulthood
Can present throughout entire adult life
Challenges arise trying to distinguish adult-onset T1DM vs much more common T2DM

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8
Q

How is Insulin produced?

A

Pro-Insulin is cleaved into insulin and C-peptide

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9
Q

What are the first stages of T1DM development?

A

Genetic predisposition, then there is a potential precipitating event

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10
Q

What is the series of events after a potential precipitating event?

A

Overt immunological abnormalities - normal insulin release
Progressive loss of insulin release - glucose still normal
Overt diabetes - C-peptide still present
No C-peptide present

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11
Q

What happens to the mass of beta-cells in the pancreases as each stage of the progression of T1DM occurs?

A

It continually declines

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12
Q

Why is the immune aspect of T1DM specifically highly clinically relevant?

A

Increased prevalence of other autoimmune disease
Risk of autoimmunity in relatives
More complete destruction of beta-cells (compared to infection etc…)
Immune modulation offers possibility of future novel treatments (none in existence yet)

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13
Q

What immunological defects lead to T1DM?

A

Presence of autoreactive CD4+ T lymphocytes
Exacerbation by pro-inflammatory cytokines
Defects in T-reg cells that fail to suppress the autoimmunity

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14
Q

How do autoreactive CD4+ cells lead to the destruction of beta-cells?

A

Auto-antigens presented to autoreactive CD4+ T lymphocytes
CD4+ cells active CD8+ cells
CD8+ cells travel to islets and lyse beta-cells
Exacerbated by release of pro-inflammatory cytokines

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15
Q

Are all beta-cells destroyed in all cases of T1DM?

A

No
Some people with T1DM have some beta-cells, small amount of insulin production
Not enough to negate need for insulin therapy however

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16
Q

Which HLA-DR alleles have an effect on genetic susceptibility to T1DM?

A

DR1-DR9

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17
Q

T1DM and T2DM are polygenic disorders, what does this mean?

A

Multiple tiny changes in a large number of genes

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18
Q

Which gene can often be used to measure genetic susceptibility?

A

HLA-DR allele

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19
Q

What does the DR1 mutation in the HLA-DR allele mean for risk level of T1DM?

A

Slight risk

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20
Q

What does the DR2 mutation in the HLA-DR allele mean for risk level of T1DM?

A

Protective

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21
Q

What does the DR3 mutation in the HLA-DR allele mean for risk level of T1DM?

A

Significant risk

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22
Q

What does the DR4 mutation in the HLA-DR allele mean for risk level of T1DM?

A

Significant risk

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23
Q

What does the DR5 mutation in the HLA-DR allele mean for risk level of T1DM?

A

Slight risk

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24
Q

What does the DR6 mutation in the HLA-DR allele mean for risk level of T1DM?

A

Neutral/protective

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25
Q

What does the DR7 mutation in the HLA-DR allele mean for risk level of T1DM?

A

Protective
Risk in African descent

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26
Q

What does the DR8 mutation in the HLA-DR allele mean for risk level of T1DM?

A

Neutral/slight risk

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27
Q

What does the DR9 mutation in the HLA-DR allele mean for risk level of T1DM?

A

Risk in far east Asian descent

28
Q

What is the significance of environmental factors in T1DM prevelance?

A

Multiple factors are implicated, causality has not been established

29
Q

Which factors have been implicated with T1DM?

A

Enteroviral infections
Cow’s milk protein exposure
Seasonal variation
Changes in microbiota

30
Q

What can be detected in the sera of people with T1DM that can confirm a diagnosis?

A

Pancreatic autoantibodies

31
Q

The presence of what substances is now recommended for T1DM diagnosis?

A

Insulin antibodies (IAA)
Glutamic acid decarboxylase antibodies (GAD-65)
Insulinoma-associated-2 antibodies (IA-2)
Zinc-transporter 8 (ZnT8)

32
Q

What are the symptoms of T1DM?

A

Polyuria
Nocturia
Polydipsia
Blurring of vision
Recurrent infections (e.g. thrush)
Weight loss
Fatigue

33
Q

What are the signs of T1DM?

A

Dehydration
Cachexia
Hyperventilation
Smell of ketones
Glycosuria
Ketonuria

34
Q

What are the effects of insulin?

A

Stimulates protein synthesis
Decreases hepatic glucose output
Inhibits lipolysis

35
Q

What are the consequences of insulin deficiency?

A

Increased proteinolysis (so more AAs)
Increased hepatic glucose output
Increased lipolysis (and so glycerol and NEFAs)

36
Q

How are ketone bodies produced?

A

Fatty Acyl-CoA in liver
Converted to acetoacetate
Then acetone + 3 OH-B
Leaves the live as ketone bodies

37
Q

What are the aims of treatment for T1DM?

A

Maintain glucose levels, without excessive hypoglycaemia
Restore a physiological insulin profile
Prevent acute metabolic decompensation
Prevent microvascular and macrovascular complications

38
Q

What are the acute complications of hyperglycaemia (in the context of diabetes)?

A

Diabetic ketoacidosis

39
Q

What are the chronic complications of hyperglycaemia (in the context of diabetes)?

A

Microvascular:
Retinopathy
Neuropathy
Nephropathy
Macrovascular:
Ischaemic heart disease
Cerebrovascular disease
Peripheral vascular disease

40
Q

Outline the managements for T1DM

A

Insulin Treatment
Dietary support / structured educations
Technology
Transplantation

Type 1 diabetes is a condition that is ‘self-managed’

41
Q

What are the main features of a physiological insulin profile?

A
42
Q

What 2 different types of insulin can be given?

A

With meals (short/quick-acting insulin)
Background (long-acting/basal)

43
Q

What is given as a short-acting insulin?

A

Human insulin – exact molecular replicate of human insulin (actrapid)
Insulin analogue (Lispro, Aspart, Glulisine)

43
Q

What is given as a long-acting insulin?

A

Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH)
Insulin analogue (Glargine, Determir, Degludec)

44
Q

What is a typical insulin routine?

A

Basal bolus regime
3x Daily - short acting - with meals
1x daily - long acting

45
Q

Outline insulin pump therapy

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 / hour throughout the day (basal)
Actively bolus for meals

46
Q

What are the principles of the dietary advice for T1DM?

A

Dose adjustment for carbohydrate content of food.
All people with type 1 diabetes should receive training for carbohydrate counting
Where possible, substitute refined carbohydrate containing foods

46
Q

What are the 2 options for transplantation to treat T1DM?

A

Islet cells transplants
Simultaneous pancreas & kidney transplants

47
Q

Outline islet cell transplants

A

Isolate human islets from pancreas of deceased donor
Transplant into hepatic portal vein

48
Q

Why is a pancreas simultaneously transplanted with kidneys?

A

Better survival of pancreas graft when transplanted with kidneys

49
Q

What is the biggest drawback for both transplantation options to treat T1DM?

A

Both require life-long immunosuppression

50
Q

How ca glucose levels be monitored?

A

Capillary (finger prick) blood glucose monitoring
Continuous glucose monitoring (restricted availability)

51
Q

Outline HbA1c

A

Reflects last 3 months (red blood cell lifespan) of glycaemia
Biased to the 30 days preceding measurement
Glycated NOT glycosylated (enzymatic)
Therefore linear relationship
Irreversible reaction

52
Q

Why is HbA1c flawed?

A

Other factors can lead to increased HbA1c

53
Q

What is used to guide insulin doses?

A

Using self-monitoring of blood glucose results at home and HbA1c results every 3-4 months
Based on results, increase or decrease insulin doses

54
Q

What are the acute complications from T1DM?

A

Diabetic ketoacidosis
Uncontrolled hyperglycaemia
Hypoglycaemia

55
Q

Outline diabetic ketoacidosis as a consequence of diabetes

A

Can be a presenting feature of new-onset type 1 diabetes
Occurs in those with established T1DM
Acute illness
Missed insulin doses
Inadequate insulin doses
Life-threatening complication
Can occur in any type of diabetes

56
Q

How can diabetic ketoacidosis be diagnosed?

A

pH <7.3
Ketones increased (urine or capillary blood)
HCO3- <15 mmol/L
Glucose >11 mmol/L

57
Q

What is the definition of hypoglycaemia?

A

Blood glucose ,3.6mmol/L (variable)

58
Q

What is the definition of severe hypoglycaemia?

A

Any hypoglycaemic event requiring 3rd party assistance

59
Q

How can hypoglycaemia become problematic?

A

Excessive frequency
Impaired awareness (unable to detect low blood glucose)
Nocturnal hypoglycaemia
Recurrent severe hypoglycaemia

60
Q

What are the risks associated with hypoglycaemia?

A

Seizure / coma/ death (dead in bed)
Impacts on emotional well-being
Impacts on driving
Impacts on day to day function
Impacts on cognition

61
Q

What may put someone with T1DM at risk of hypoglycaemia?

A

Exercise
Missed meals
Inappropriate insulin regime
Alcohol intake
Lower HbA1c
Lack of training around dose-adjustment for meals

62
Q

What strategies can be used to support problematic hypoglycaemia?

A

Indication for insulin-pump therapy (CSII)
May try different insulin analogues
Revisit carbohydrate counting / structured education
Behavioral psychology support
Transplantation

63
Q

What is used for the acute management of hypoglycaemia when someone is alert and orientated?

A
64
Q

What is used for the acute management of hypoglycaemia when someone is Drowsy / confused but swallow intact?

A
65
Q

What is used for the acute management of hypoglycaemia when someone is Unconscious or concerned about swallow?

A