Guidelines for Genetic Testing in MODY

Patients with isolated diabetes should be tested if they have:

a)      Diabetes diagnosed young (≤35 years in White Europeans and ≤30 years in high prevalence ethnic groups like South Asians).

AND

b)      Unlikely to have Type 1 diabetes because:

They are not on insulin treatment.

OR

They are on insulin treatment with all autoantibodies tested negative (minimum testing of GADA and IA2A) and a random non-fasting C peptide value ≥200pmol/L (The Exeter Blood Sciences laboratory can offer this testing if it is not available at your local laboratory. Please see their website and contact them for further details https://www.exeterlaboratory.com/test/gad-antibodies/ and https://www.exeterlaboratory.com/test/c-peptide-urine/).

AND

c)       Have features suggestive of MODY:

An HbA1c at diagnosis of diabetes <7.5% (58mmol/mol), if diagnosed under 18 years of age,

OR

BMI <30kg/m2 adult (child BMI <95th centile) and a parent with diabetes (if White) or BMI <27kg/m2 (child BMI <95th centile) and a parent with diabetes (if high prevalence type 2 diabetes ethnic group).

OR

Have a MODY probability score ≥20% if not insulin treated and ≥10% if insulin treated (see the MODY calculator)

Referrals will be triaged by the Genomic laboratory. Testing is targeted at those where a genetic diagnosis will guide management for the proband or family. HbA1c and fasting glucose results must be available prior to genetic testing.

a) Fasting glucose noted to be raised ≤35 years

AND

b) Asymptomatic stable fasting hyperglycaemia (5.5-8mmol/L) (minimum 2 independent laboratory fasting blood glucose test results)

OR

c) HbA1c 36-58mmol/mol (5.5-7.5%)

Testing criteria in pregnancy

a) Gestational diabetes with fasting glucose 5.5-8mmol/l.

AND

d) BMI <30kg/m2 if white, or BMI <27kg/m2 , if high prevalence type 2 diabetes ethnic group.

Features that support a diagnosis in pregnancy: persistent fasting hyperglycaemia post pregnancy or previous babies with normal birthweight despite maternal hyperglycaemia.

All patients diagnosed with diabetes diagnosed less than 9 months of age

Marked hyperglycaemia is common in very preterm patients due to an immature pancreas. These individuals should be referred for genetic testing only if hyperglycaemia requiring insulin treatment is still present at 32 weeks equivalent gestational age.

Diabetes diagnosed young

AND

• Unlikely to have type 1 diabetes (see 1.0) or type 2 diabetes.

AND

• Non-autoimmune extra pancreatic features suggestive of syndromic monogenic diabetes e.g.

• Cystic renal disease and/or congenital anomaly of kidney or urinary tract
• Bilateral sensorineural deafness
• Developmental delay
• Developmental defects
• Cardiomyopathy
• Optic atrophy
• Microcephaly

Patients have features of severe insulin resistance in the absence of obesity:

Acanthosis nigricans

OR

A fasting insulin >150pmol/l if not insulin treated OR if insulin treated an insulin requirement >3U/kg/day

AND

Diabetes that is unlikely to be type 1 diabetes (see 1.0 above) or type 2 diabetes (BMI<30kg/m2 if white (<95th in children) or BMI <27kg/m2 (<95th in children) if high prevalence type 2 diabetes group).