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Flashcards in Lecture 4 Deck (15)
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1
Q

What is type 1 diabetes caused by?

A

Diminished or absent beta cell function

2
Q

What is type 2 diabetes caused by?

A

Resistance to insulin, increase in production and eventually the pancreas is exhausted, and secretion reduces

3
Q

What is the treatment for type 1 diabetes?

A

Insulin, blood glucose meter, education, carbohydrate counting

4
Q

What is the treatment for type 2 diabetes

A

Metformin, tablets, no routine glucose testing, education, diff insulin regimes

5
Q

What are some examples of monogenic diabetes?

A

MODY - collection of autosomal dominant monogenic disorders affecting genes involved in beta cell glucose sensing and insulin secretion

PND - Permanent neonatal diabetes - occurs in the first 6 months of life and mutations are spontaneous

6
Q

What is HNF1 alpha mutation (MODY)?

A

Transcription factor normally stimulating insulin production
In absence, insulin production reduced, but only manifests in adulthood when beta- cell function starts to naturally decline. Best managed by sulphonylureas and when diagnosed insulin can be stopped. May eventually need insulin. Future risk of micro/macrovascular problems.

7
Q

What is glucokinase MODY

A

Beta cell glucose sensor, mutations mean there is a higher set point at which insulin secretion starts. Patients have same relationship as age changes as normal individuals. Mild life long, non- progressive hyperglycaemia. No long- term complications, treatment not needed

8
Q

What is the KCNJ11 mutation (PND)?

A

Normally glucose enters via the transporter and is converted via glycolysis by hexokinase. The ATP that is made closes the K+ channel (made of two subunits, including sur 1). Then the membrane depolarises and there is calcium influx and the granules containing insulin are released.
KNCJ11 mutation causes the channel to stay open, membrane hyper-polarised and calcium doesn’t enter.

9
Q

What is the treatment for PND (KCNJ11 mutation)?

A

Sulphonylureas – Binds to the sur1 subunit force closing the membrane and insulin can be secreted

10
Q

What are the three main stages involved in genetic testing?

A

1) Decide genetic testing appropriate

2) Genetic counseling
Pros and cons of testing
Impact on treatment
Impact on family members

3)Blood test
Next generation sequencing technologies
Confirmation via Sanger sequencing

11
Q

What is mitochondrial diabetes?

A

Maternally transmitted, causes diabetes, high lactate, muscle aches, shortness, young onset sensorineural deafness. UNDERDIAGNOSED

12
Q

Monogenic vs polygenic diabetes treatment differences

A

monogenic:

  • sulfonylureas
  • diet
  • exercise
  • may not need anything else

polygenic:

  • metformin
  • diet
  • exercise
  • insulin
13
Q

What is the relevance of GWAS/SNPs in diabetes?

A

In type 1 diabetes the HLA SNP has an odds ratio of 6.5
Type 2 diabetes there are about 90 loci involved but the effects are very small
Effects are not significant especially for type 2 diabetes so not useful to clinicians.

14
Q

Give examples of polygenic diabetes

A

Type 1 and Type 2 diabetes

15
Q

What are some rarer types of MODY?

A

HNF4 alpha, HNF1 beta