Type 2 diabetes can also be multigenerational like MODY

Abstract

Type 2 diabetes (T2DM) is now known to comprise of a heterogeneous group of metabolic disorders. The common garden variety of T2DM with onset in adult life is a multifactorial or polygenic disorder with multiple genes each playing a relatively minor role towards the overall risk of T2DM [1]. In addition, there is a large environmental component. Familial aggregation of T2DM is well known, and up to 40–60% of T2DM patients may have a family history of diabetes in a first degree relative [2]. This figure would obviously be higher if all the relatives were screened for diabetes rather than based on ‘known’ family history of diabetes. Multigenerational diabetes, with an autosomal dominant type of inheritance, is common in the monogenic forms of diabetes like Maturity Onset Diabetes of the Young (MODY) [3, 4]. Patients with MODY, typically have a diabetic parent and a grandparent, and often a great grandparent on the affected parent’s side with diabetes, suggestive of autosomal dominant inheritance [5]. MODY type diabetes, is now classified into at least 6 distinct types (MODY-1 to MODY-6) based on the specific genetic mutation involved, although newer MODY types continue to be described [6, 7]. MODY 3 (due to HNF1- ∝ mutations) is the commonest form of MODY followed by MODY-1 (due to HNF-4 ∝ mutations) and together they are believed to comprise up to 75% of adult onset MODYamong Europeans [3, 4, 6]