1. Identifying monogenic diabetes
Agnieszka Graja
RGN, MSc
Genetic Diabetes Nurse
7th November 2016

2. What might suggest your patient has monogenic diabetes ?
Diabetes diagnosed <6 months of age
Diabetes diagnosed below 25 years of age and a parent with diabetes
Diabetes plus e.g. RCAD, MIDD, DEND
What else might help determine whether
your patient has monogenic diabetes ?

3. Islet antibodies 508 MODY patients and 98 newly diagnosed Type 1
Costs £20, new cut offs established in 500 controls. Those GAD + with MODY may reflect 1-2% of normal population who are antibody +.
GAD and IA2 both automated standardised tests through accredited lab (high quality)
McDonald T et al (2011) Diabet Med 3

4. UCPCR can aid differentiate between Type 1 and MODY
Urinary C-Peptide Creatinine Ratio
UCPCR: Most useful outside honeymoon period, post prandial sample can be posted
<0.2 nmol/mmol indicates insulin deficiency
Besser R et al (2011) Diabetes Care

6. Example in practice Insulin treated from diagnosis 0.7% Female
Probability of MODY
Insulin treated from diagnosis
0.7%
Female
Diagnosed age 19, now 30
Parent with diabetes
HbA1c 7.9%
BMI 28 kg/m2
6.3%
So we’ve produced probability models for combining predictors of MODY but how can we use these in clinical practice? Well if we take an example of a patient This patient is insulin treated from diagnosis. Based on this information alone, we estimate their probability of MODY to be 0.7%. They are female, diagnosed aged 19, now 30. They have a parent with diabetes, an hba1c of 7.9% and a BMI of 28. If we add these characteristics to the clinical prediction model we get a probability of MODY of 6.3%. If however, we then found out they were negative for C-peptide, so not producing their own insulin, the probability of them having MODY would then go down to 1%. If on top of this, we found out they were positive for GAD antibodies then their probability would go down to 0.01%, so a 1 in 10,000 chance.
C-peptide negative
1.0%
GAD positive
0.01%

7. Example in practice Insulin treated from diagnosis 0.7% Female
Probability of MODY
Insulin treated from diagnosis
0.7%
Female
Diagnosed age 19, now 30
Parent with diabetes
HbA1c 7.9%
BMI 28 kg/m2
6.3%
C-peptide negative
positive
1.0%
15.6%
GAD positive
GAD/IA2 negative
0.01%
51.5%

8. How do you refer a patient for genetic testing ?
Download a ‘Diagnostic request form’ from
Complete form and send with EDTA sample to Exeter
Discuss case if unsure
(with myself)
Costs apply for genetic testing (except neonatal diabetes) but agreed by UKGTN as appropriate for all meeting criteria

9. Maturity-onset diabetes of the young (MODY): in the post genetic era
22% Glucokinase
66% Transcription factors
<1% Insulin
<1% SUR1
11% MODY x
2% HNF1B
61% HNF1A
4% HNF4A
<1% IPF1
<1% CEL

10. Defining the gene helps diagnosis
Clinical features
Specific beta-cell
defect
Finding gene mutation
Makes diagnosis
Pathophysiology
Treatment
Response

11. 66% Transcription factors
In Maturity-Onset Diabetes of the Young
(MODY) genetic subtype determines clinical picture and treatment response
MODY
22% Glucokinase
66% Transcription factors
<1% CEL
<1% Insulin
11% MODY x
2% HNF1
61% HNF1
4% HNF4 
<1% IPF1
<1% NeuroD1
Treatment not needed
Insulin
Low dose SUs
Insulin
?too rare

12. Family tree Pancreatic antibodies ‘Negative’ UCPCR ‘Positive’
Talk through family tree and autosomal dominant inheritance
UCPCR ‘Positive’

13. When to consider monogenic diabetes
Anyone diagnosed <25 years with an affected parent :
Autosomal dominant inheritance,
Young age of onset (<25 yrs),
Non insulin dependent diabetes
Anyone diagnosed ‘young’ with other features associated with monogenic diabetes e.g.
mild stable hyperglycaemia, HbA1c 40-60mmol/mol (GCK)
macrosomia, neonatal hypoglycaemia (HNF4A)
low renal threshold for glucose, SU sensitivity, early MI (HNF1A)
diabetes and deafness, maternal inheritance (MIDD)
diabetes and renal cysts, single kidney, bicornate uterus (HNF1B)
Anyone diagnosed <6 months of age (neonatal diabetes)

14. Monogenic Diabetes Symposium on 8-9th Feb 2017
For more information about monogenic diabetes please visit our website:
If you would like to learn more please register for our
Monogenic Diabetes Symposium on 8-9th Feb 2017