MODY

Last edited 10/2023 and last reviewed 11/2023

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 (1,2).

• there is β cell dysfunction characterised by non-ketotic diabetes and absence of pancreatic auto-antibodies (3)

The condition was first described by Tattersall in 1974–1975, a familial form of non-insulin dependent diabetes which showed autosomal dominant inheritance which presented before the age of 25 years (1,2). The molecular genetic basis of MODY was subsequently recognised in the 1990s and mutations in 10 different genes have been identified so far (2).

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

• 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 diagnosed.
• 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%  (3)

On-line MODY calculator

Study evidence concluded that (4):

• MODY probability calculator shows good discrimination between monogenic and the more common type 1 and type 2 diabetes in a highly pre-selected group of Portuguese individuals diagnosed under the age of 35
• provides a useful tool for selecting patients for genetic testing, but its 35 years at diagnosis age cut-off constitutes a major weakness, decreasing its sensitivity

Reference:

• (1) Gardner DS, Tai ES. Clinical features and treatment of maturity onset diabetes of the young (MODY). Diabetes Metab Syndr Obes. 2012;5:101-8.
• (2) Thanabalasingham G, Owen KR. Diagnosis and management of maturity onset diabetes of the young (MODY). BMJ. 2011;343:d6044
• (3) Nyunt O et al. Investigating maturity onset diabetes of the young. Clin Biochem Rev. 2009;30(2):67-74
• (4) da Silva Santos T, Fonseca L, Santos Monteiro S, Borges Duarte D, Martins Lopes A, Couto de Carvalho A, Oliveira MJ, Borges T, Laranjeira F, Couce ML, Cardoso MH. MODY probability calculator utility in individuals' selection for genetic testing: Its accuracy and performance. Endocrinol Diabetes Metab. 2022 Sep;5(5):e00332.