Synopsis
Recognise monogenic diabetes phenotypes, select NHS genomic testing appropriately, and translate a confirmed molecular diagnosis into safe person- and family-specific care.
- Monogenic diabetes results from a single-gene disorder and should be suspected when the phenotype does not fit common type 1 or type 2 mechanisms.
- Clues include diagnosis young in life, diabetes in successive generations, negative autoantibodies, persistent endogenous insulin secretion and gene-specific extra-pancreatic features.
- GCK-related hyperglycaemia is usually lifelong, mild and stable, often with fasting glucose around 5.5–8 mmol/L; treatment is generally unnecessary outside specialist pregnancy decisions.
Investigation priorities
Define inheritance, age at onset, treatment, neonatal history and extra-pancreatic features before genomic selection.
Management branches
Diabetes age, family pattern or syndromic features do not fit routine type 1 or type 2 classification.
- Construct a three-generation pedigree and record exact diagnosis ages, therapies, birth histories, renal, hearing, neurological and pregnancy features.
- Review autoantibodies, paired C-peptide, HbA1c trajectory and current insulin safety, treating any active deficiency without waiting for genomic results.
Key medicines
Sulfonylurea for HNF1A or HNF4A diabetesBegin only after specialist confirmation, using a lower-than-usual oral starting dose and slow titration against glucose because marked sensitivity is common; insulin transfer requires close supervision.
InsulinUse an individual basal-bolus, pump or neonatal specialist regimen according to current secretion, age, nutrition, pregnancy and glucose patterns; any reduction after genetic diagnosis must be supervised.