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AE > 3 - T2DM > Flashcards

3 - T2DM Flashcards

1
Q

What are the 4 main risk factors for T2DM?

A

1) Diet
2) Obesity
3) Sedentary lifestyle
4) Genetic predisposition

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2
Q

What are the 2 components that eventually result in T2DM?

A

1) Insulin resistance

2) Beta-cell dysfunction

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3
Q

What two properties characterise insulin resistance?

A

Increasing peripheral insulin resistance

Increasing hepatic glucose output

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4
Q

What two properties characterise Beta-cell dysfunction?

A

Inability to compensate for increasing insulin resistance

Impaired insulin secretion

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5
Q

In the context of genetic risk factors, what 2 properties in the aetiology of T2DM are most commonly affected?

A

Beta-cell function

Beta-cell mass

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6
Q

What is the term for when the environment has an effect on genetics?

A

Epigenetics

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7
Q

What two genes have been shown to be very important in acting as a predisposition to T2DM?

A

TCF7L2

KCNJ11

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8
Q

What is the effect of a mutated TCF7L2 gene?

A

Mutation in transcription factor involved in incretin signalling, therefore:

= Decreased incretin signalling

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9
Q

What is the effect of a mutated KCNJ11?

A

Codes for the K-ATP channel which is involved in insulin secretion.

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10
Q

What are the 5 areas in which mutations can occur and predispose T2DM?

A

1) Ion channels / transporters
2) Glucose metabolism
3) Insulin gene transcription
4) Packaging insulin in vesicles
5) Incretins

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11
Q

When are epigenetic factors most likely to have an effect on an individual?

A

In utero

Soon after birth

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12
Q

Name 1 example of epigenetic effects on T2DM

A

Dutch famine - 1944-1945

Low birth weight (from famine) associated with insulin resistance and diabetes.

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13
Q

In the case of the Dutch famine, what was also noticed and concluded from Diabetic mothers having children?

A

Children ALSO at high risk of diabetes development.

Epigenetic factors can be inherited!

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14
Q

What are the two main contributing processes to epigenetic coding?

A

1) DNA Methylation (represses gene activity)

2) Histone modification (alter DNA around)

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15
Q

What gene has been linked to intra-uterine growth retardation in development of T2DM?

What is that gene’s function?

A

Pdx1 = transcription factor essential for proper beta-cell development + reduced beta-cell mass.

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16
Q

What is the MOST important factor in the development of diabetes?

A

Diet

subsequently, adiposity –> obesity

17
Q

30 minutes of physical activity has what effect on T2DM risk?

A

Halves

18
Q

In the context of fat distribution, what factor is most important?

A

Visceral adiposity is much more dangerous.

19
Q

What is the mechanism of insulin resistance?

A

1) Build up of toxins from glucose / lipid metabolism.

Then has effects on either:

  • No. of insulin receptors
  • Insulin receptor function (e.g. autophosphorylation / tyrosine kinase activity)
  • Downstream signalling changes
  • Translocation of GLUT4 channel (important for uptake)

= insulin resistance.

20
Q

What is the proposed hypothesis to T2DM pathophysiology?

A

As weight increases from increased dietary intake, Beta-cell mass can increase by compensation (NGT)

This continues until beta-cell dysfunction occurs = (IGT)

Occurring until beta-cell failure = (T2DM)

NGT - normal glucose tolerance

IGT - impaired glucose tolerance

21
Q

What are the 4 groups of medications for T2DM?

A

Insulin secretagogues
Incretin therapies
Insulin sensitisers
Reduce glucose supply

22
Q

Give 2 classes of drugs that are insulin secretagogues

A

Sulphonylureas

Meglitinides

23
Q

Give 2 classes of drugs that are incretin therapies

A

GLP-1 receptor agonists

DPP-IV inhibitors

24
Q

Give 2 classes of drugs that are insulin sensitisers

A

Thiazolidinediones

Biguanides

25
Q

Give 3 classes of drugs that reduce glucose supply

A

Alpha-glucosidases
Amylin analogues
SGLT2 inhibitors

26
Q

Give an example of a DPP4 inhibitor

A

Sitagliptin

27
Q

Name the example of a biguanide

A

Metformin

28
Q

Name the example of thiazolidodinediones

A

Pioglitazone

29
Q

Name an example of an alpha-glucosidase

A

Acarbose

30
Q

Name an example of an amylin analogue

A

Pramlintide

31
Q

Name an example of an SGLT2 inhibitor

A

Canagliflozin

32
Q

Why don’t SGLT2 inhibitors cause hypoglycaemia?

A

Because of SGLT1 which is found in segments S2 and S3 of kidney have HIGH affinity so still reabsorb glucose.

AE (7 decks)

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