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AE > 3 - T1DM > Flashcards

3 - T1DM Flashcards

1
Q

Define diabetes mellitus

A

Hypergycaemia

Caused by insufficient:

  • Insulin secretion
  • Insulin action

Associated with significant morbidity / mortality

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2
Q

In Caucasian Northern Europe, what is the most common aetiology of T1DM?

A

T-cell mediated autoimmune destruction of the Beta-cells within the pancreas.

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3
Q

How many people in the UK are diagnosed with DM?

A

4.7 million

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4
Q

How many are estimated to have DM by 2035?

A

> 5 million

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5
Q

How many people have been diagnosed with diabetes worldwide?

A

425 million

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6
Q

How much does diabetes cost the UK?

A

£10 billion

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7
Q

What % of this £10 billion is spent on preventable complications?

A

80%

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8
Q

What % of TOTAL NHS budget is spent on diabetes and complications?

A

10%

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9
Q

By 2035, what is the projected % spend of TOTAL NHS budget on diabetes and complications?

A

17%

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10
Q

What are the symptoms of diabetes?

A 
Polyuria
Polydipsia
Unexplained weight loss
Tiredness
Blurred vision
Diabetic ketoacidosis
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11
Q

How do you diagnose diabetes?

A

Either:

Fasting plasma glucose > 7.0 mmol/L

Random plasma glucose > 11.1 mmol/L

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12
Q

What is the gold standard for diabetes diagnosis?

A

Oral glucose tolerance test (OGTT) - 75g of glucose.

2h-post glucose-load plasma glucose > 11.1mmol/L

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13
Q

What test is required if patient is asymptomatic but blood glucose levels are suggestive of diabetes?

A

Repeat glucose measurement on a different day to confirm.

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14
Q

Why is misdiagnosing diabetes dangerous?

A

Affect life insurance
Ability to drive
Perform employment duties

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15
Q

Who is HbA1c not possible to use as a clinical diagnostic test?

A

Young people
T1DM
Pregnant
Haemoglobinopathies

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16
Q

What does HbA1c measure?

A

Measures glycated haemoglobin.

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17
Q

What are the 3 advantages of HbA1c?

A

1) No need to fast
2) Lower variability
3) More stable for transporting samples

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18
Q

What are the reference ranges for HbA1c?

A

<42mmol/L = normal

42-47 = pre-diabetes

> 47 = diabetes

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19
Q

What are the 2 features of a pancreatic beta cell?

A

Nucleus

Insulin secretory granules (fried eggs)

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20
Q

What are the 2 components of an insulin secretory granule?

A

Dense insulin core

Loose surrounding zone

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21
Q

In the production of insulin, what is the role of the ER?

A

ER produces a pro-hormone.

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22
Q

What is the role of the golgi apparatus in the production of insulin?

A

Cleaves the pro-hormone by pro-hormone-convertases

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23
Q

What pro-hormone convertases are present in the golgi apparatus?

A

PC2 and PC1/3

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24
Q

What are the two products of pro-hormone insulin cleavage?

A

1) Mature insulin

2) C-peptide

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25
Q

Which cells produce insulin?

A

Beta cells in the pancreatic islets of langerhans

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26
Q

Which cells produce glucagon?

A

Alpha cells

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27
Q

What are the 3 main targets of insulin / glucagon?

A

Muscle
Liver
Adipose tissue

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28
Q

What glucose transporter is responsible for bringing glucose into the beta cell?

A

GLUT1

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29
Q

Describe the process of insulin secretion.

A

Glucose transport into cell

Metabolism produces ATP

ATP-sensitive K+ channels close, resulting in depolarisation.

Voltage-gated calcium channels open, resulting in calcium influx.

Insulin secretory granules exocytosed

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30
Q

What is the incretin effect?

A

The markedly higher insulin response when glucose is ingested compared to when given through IV

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31
Q

Give 2 examples of an incretin?

A

GLP-1

GIP

32
Q

What cells produce GLP-1?

A

Intestinal L-cells

33
Q

What type of GPCR is GLP-1 receptor?

A

GalphaS

34
Q

What pattern of insulin secretion occurs? What is it described as?

A

Biphasic

1st phase: Triggering stimulus releases granules already close to membrane of beta-cell immediately.

2nd phase: Expansion and replenishment of readily-releasable pool before second wave of insulin secretion.

35
Q

What is PDX1?

What occurs in high glucose levels?

A

A transcription factor regulated by glucose

PDX1 activated to increase transcription of insulin gene.

36
Q

What are the two pathways that are activated in response to insulin-receptor activation?

A

PI3K pathway

RAS/MAPK pathway

37
Q

What subsequent processes is the PI3K pathway involved in?

A

Growth + differentiation

+ Metabolic actions

38
Q

What subsequent processes is the RAS/MAPK pathway involved in?

A

Growth + differentiation

Survival + Gene expression

39
Q

What are the 2 differences between T1A-DM and T1B-DM?

A

No autoimmune markers detectable in T1B-DM.

T1A = insulin deficiency
T1B = Absolute deficiency
40
Q

What 3 features are associated with T2DM?

A

Beta-cell failure / insulin resistance.

Later presentation

Associated with obesity

41
Q

What is gestational diabetes mellitus?

A

Glucose intolerance / diabetes during pregnancy.

42
Q

When does gestational diabetes mellitus usually occur?

A

During 2nd / 3rd trimester

43
Q

Following parturition after gestational diabetes mellitus, what is the outcome in the context of the mother’s DM?

A

Can NOT have DM.

Will be at a higher risk of getting it.

44
Q

What is maturity onset diabetes of the young? (MODY)

A

Monogenic cause of diabetes that occurs in young-adult life, as a result of a mutation in a gene responsible for pancreatic beta cell function, differentiation or proliferation.

45
Q

Give 3 examples of genes that, if mutated, result in Maturity onset diabetes of the young (MODY)

A

Glucokinase
PDX1
HNF-1alpha

46
Q

How is MODY diagnosed?

A

<25 years old

Familial inheritance

47
Q

What % of DM patients have MODY?

A

1-2%

48
Q

What is permanent neonatal DM ?(PNDM)

A

Monogenic cause of diabetes that occurs following birth.

49
Q

What two important genes can cause permanent neonatal DM? What are they responsible in coding for?

A

KCNJ11 / ABCC8

The ATP-sensitive K+ ion channel

50
Q

What is an emergency complication of T1DM?

A

DKA

51
Q

What is the T2DM equivalent of DKA?

A

Hyperosmolar non-ketotic coma (HONK)

52
Q

What are two important genes in the predisposition of T1DM?

A

HLA DR4

HLA DR3

53
Q

What percentage of children with T1A-DM have either one of HLA-DR3/4?

A

90%

54
Q

What is the original gene and its location in regard to HLA DR3/4?

A

HLA Class II

Chromosome 6

55
Q

What does HLA stand for?

A

Human Leukocyte Associated

56
Q

What are the 3 classes of HLA genes?

A

Class 1 = all nucleated cells (necessary for viral infection response)

Class 2 = APC cells

Class 3 = Complement

57
Q

What factors can trigger T1DM?

A 
Viruses
Bacteria
Gluten
Toxins
Cow's milk
58
Q

What viruses can trigger T1DM?

A

Coxsackie B4 virus

Picornavirus

59
Q

What is the usual natural history of the disease and its progression?

A

A progressive decline in insulin secretory capacity, as a result of continual auto-immune destruction of Beta-cells.

60
Q

In the pathogenesis of T1DM, what is the honeymoon phase?

A

Occurs after first hyperglycaemia.

Pancreatic beta-cells and pancreatic stem cells regenerate themselves to increase beta-cell mass and normalise glucose level.

However, quickly gets overrun by autoimmune disease again.

61
Q

What % of T1DM patients have the presence of autoantibodies circulating in their blood?

A

90%

62
Q

What are autoantibodies a predictor of?

A

Risk of T1DM development.

63
Q

Name the 4 auto-antibodies commonly found in

A

GAD65
Islet antigen-2
Insulin
Zinc transporter

64
Q

What is Insulitis?

A

Invasion of pancreatic islets by lymphocytes (CD4+ / CD8+).

Characteristic of T1DM

65
Q

How do you treat T1DM?

A

Insulin

66
Q

How is insulin administration given to match normal physiology?

A

Basal dose

Short-acting insulin analogue following meal consumption.

67
Q

Give 2 examples of long-acting insulin analogues

A

Glargine

Detemir

(1x daily)

68
Q

Give 2 examples of short-acting insulin analogues

A

Lispro

Aspart

69
Q

What are 4 other methods of treating T1DM?

A

Kidney / pancreas transplant

Insulin pumps (open / closed)

Islet transplant

Insulin inhalation

70
Q

What is an issue with islet transplantation?

A

Requires 3 donors

Remission lasts 5 years before it occurs again.

71
Q

What are the 4 future treatments for T1DM?

A

· Advanced closed-loop insulin pumps

· Cell-based therapies: islet transplantation (ongoing trials), stem cell therapies

· β-cell regenerative medicine

· Prevention / immune modulation

72
Q

What is the bionic pancreas and how does it work?

A

Real time insulin / glucagon pump that alleviates the major clinical / personal issues that are bound to T1DM.

Blood glucose monitor and doses insulin / glucagon in relative amounts every 5 minutes.

Catheter requires changing weekly.

73
Q

What is T1DM?

A

Absolute deficiency of insulin.

74
Q

If diagnosis of T1DM occurs before 1 year of age, what two genetic conditions should be considered?

A

Maturity onset diabetes of the young

or other monogenic causes of diabetes, e.g. permanent neonatal diabetes mellitus

75
Q

What is hypoglycaemia defined as in regards to blood glucose concentrations, in mmol/L?

A

<3.5mmol/L

AE (7 decks)

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