Monogenic Diabetes

Question 1

What are the three key tests in order to determine whether a patient has type 1 diabetes or not?

Answer 1

• Pancreatic autoantibodies
• C-peptide testing
• Genetic Risk Score
  (Age & BMI)

Question 2

What three autoantibodies are tested?

Answer 2

• GAD
• IA-2
• ZnT8

Question 3

How sensitivity is the autoantibody test?

Answer 3

Alone they have low sensitivity but combined they have 95% sensitivity

Question 4

What is the pattern of progression of c-peptide in type 1 diabetes?

Answer 4

High at diagnosis but decreases over the course of 3 years (children) 5 years (adults)

Question 5

When would it be best to measure random/post meal & paired glucose?

Answer 5

• when testing for type 1 diabetes

- when testing endogenous c-peptide production

Question 6

When would it bbd best to measure fasting c-peptide/fasting glucose?

Answer 6

• testing for insulin resistance

- determining insulin required for euglycaemia

Question 7

State a better way to measure c-peptide in children

Answer 7

Urine

Question 8

Describe genetic risk score

Answer 8

Uses centiles & sum of risk increasing alleles to measure genetic predisposition of type 1 diabetes.
High score –> T1DM likely
Low score –> T1DM unlikely

Question 9

State two other factors that can help (are not definite) to distinguish between types of diabetes

Answer 9

Age & BMI

Question 10

Name two types of monogenic diabetes

Answer 10

• maturity consent diabetes of the young (MODY)

- neonatal diabetes

Question 11

What are the three subtypes of MODY?

Answer 11

• Glucokinase mutations
• Transcription factors mutations
• MODY x

Question 12

What are the three most common transcription factors mutation?

Answer 12

HNF1 alpha
HNF4 alpha
HNF1 beta

Question 13

Describe glucokinase mutations

Answer 13

heterozygous defect - beta cells work fine but resort to hexokinase as a alternative. As a result of the Km insulin is released at a higher glucose level.

Question 14

How does a glucokinase mutation present?

Answer 14

High glucose from birth

Question 15

Does glucokinase mutation require treatment?

Answer 15

No

Question 16

When may problems arise in patients with a glucokinase mutation?

Answer 16

Pregnancy

Question 17

What age does MODY usually present?

Answer 17

Before 25 years old

Question 18

How do transcription factor mutations present?

Answer 18

Adolescence/young adults with progressive hyperglycaemia - can be frequent complications

Question 19

Where does the defect occur in transcription factor mutations?

Answer 19

Before the KATP channel (meaning no ATP is generated to block it and depolarisation cannot occur)

Question 20

What is the treatment for transcription factor mutations?

Answer 20

Sulfonylureas - bypass defect and block the channel

Question 21

How sensitive are transcription factor mutations to sulfonylureas?

Answer 21

Highly

Question 22

What treatment does neonatal diabetes require?

Answer 22

Insulin treatment within first 3 months of life

Question 23

Name the two types of neonatal diabetes

Answer 23

• transient

- permeant

Question 24

Describe transient neonatal diabetes

Answer 24

diagnosed <1 week old, resolves after 12 weeks but usually comes back in teenage years

Question 25

Describe permeant neonatal diabetes

Answer 25

diagnosed 0-6 weeks and lifelong insulin is required

Question 26

In neonatal diabetes what to 50% of cases have a problem with?

Answer 26

Kir subunit of the KATP channel, lack of response to ATP leads to no depolarisation and no insulin release

Question 27

What is the treatment for KIR mutations?

Answer 27

Sulfonylureas - open channels and cause depolarisation and insulin release