Monogenic Diabetes Flashcards
What are the three key tests in order to determine whether a patient has type 1 diabetes or not?
- Pancreatic autoantibodies
- C-peptide testing
- Genetic Risk Score
(Age & BMI)
What three autoantibodies are tested?
- GAD
- IA-2
- ZnT8
How sensitivity is the autoantibody test?
Alone they have low sensitivity but combined they have 95% sensitivity
What is the pattern of progression of c-peptide in type 1 diabetes?
High at diagnosis but decreases over the course of 3 years (children) 5 years (adults)
When would it be best to measure random/post meal & paired glucose?
- when testing for type 1 diabetes
- when testing endogenous c-peptide production
When would it bbd best to measure fasting c-peptide/fasting glucose?
- testing for insulin resistance
- determining insulin required for euglycaemia
State a better way to measure c-peptide in children
Urine
Describe genetic risk score
Uses centiles & sum of risk increasing alleles to measure genetic predisposition of type 1 diabetes.
High score –> T1DM likely
Low score –> T1DM unlikely
State two other factors that can help (are not definite) to distinguish between types of diabetes
Age & BMI
Name two types of monogenic diabetes
- maturity consent diabetes of the young (MODY)
- neonatal diabetes
What are the three subtypes of MODY?
- Glucokinase mutations
- Transcription factors mutations
- MODY x
What are the three most common transcription factors mutation?
HNF1 alpha
HNF4 alpha
HNF1 beta
Describe glucokinase mutations
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.
How does a glucokinase mutation present?
High glucose from birth
Does glucokinase mutation require treatment?
No
When may problems arise in patients with a glucokinase mutation?
Pregnancy
What age does MODY usually present?
Before 25 years old
How do transcription factor mutations present?
Adolescence/young adults with progressive hyperglycaemia - can be frequent complications
Where does the defect occur in transcription factor mutations?
Before the KATP channel (meaning no ATP is generated to block it and depolarisation cannot occur)
What is the treatment for transcription factor mutations?
Sulfonylureas - bypass defect and block the channel
How sensitive are transcription factor mutations to sulfonylureas?
Highly
What treatment does neonatal diabetes require?
Insulin treatment within first 3 months of life
Name the two types of neonatal diabetes
- transient
- permeant
Describe transient neonatal diabetes
diagnosed <1 week old, resolves after 12 weeks but usually comes back in teenage years
