Common subtypes of MODY

Maturity onset diabetes of the young (MODY) is a heterogeneous group of monogenic disorders distinct from type 1 (insulin-dependent) and type 2 (noninsulin-dependent) diabetes (1).

• there is β cell dysfunction characterised by non-ketotic diabetes and absence of pancreatic auto-antibodies (2)
  
  

common subtypes of MODY

Clinical presentation, prognosis, and treatment response varies with the subtype of MODY e.g. -

• GCK
  • often asymptomatic and recognised during routine screening
  • there is mild, stable fasting hyperglycaemia (5.5 - 8 mmol/L)
  • majority maintain glycated hemoglobin (HbA1c level) below 8%,
  • around 2% require insulin therapy
  • complications are rare
  • about 50% of female carriers develop gestational diabetes (2)
    
    
• HNF1A
  • most common cause of MODY in the UK
  • there is progressive beta cell failure and increasing hyperglycemia
  • low renal threshold for glycosuria
  • raised HDL-C levels are seen which will differentiate MODY with type 2 diabetes
  • marked sensitivity to sulfonylureas
  • considerable risk of microvascular and macrovascular complications
    
    
• HNF4A
  • usually are normoglycaemic in childhood but progressive beta cell dysfunction results in diabetes during the second to fifth decades
  • treatment requirement increases with time and may require insulin therapy
  • vulnerable to the microvascular and macrovascular complications associated with diabetes
  • macrosomia and neonatal hypoglycaemia have also been reported
  • tight control sugar and other cardiovascular risk factors are vital in long term care

Prevalence of MODY is unknown but the minimum UK population prevalence of all MODY subtypes is estimated to be 68-108 cases per million.

Notes:

• the prevalence of MODY subtypes differ from country to country
  • in countries such as France, Spain, and Italy where glucose testing of asymptomatic people is done routinely, glucokinase (GCK) mutations are commonly diagnosed while in countries where random blood glucose tests are seldom done hepatocyte nuclear factor 1α (HNF1A) is commonly daiagnosed.
• in the UK, most common causes of mutations of MODY are
  • glucokinase (GCK) - 32%
  • hepatocyte nuclear factor 1α (HNF1A) - 52%
  • hepatocyte nuclear factor 4α (HNF4A) - 10% (2)

Reference:

• (1) Thanabalasingham G, Owen KR. Diagnosis and management of maturity onset diabetes of the young (MODY). BMJ. 2011;343:d6044
• (2) Nyunt O et al. Investigating maturity onset diabetes of the young. Clin Biochem Rev. 2009;30(2):67-74