Understanding the genetic mechanisms of diabetes mellitus in children with complex novel syndromes

Supervisors: Dr Khalid Hussain and Dr Detlef Bockenhauer

Diabetes mellitus (DM) is common in the paediatric population. Type 1 DM is the most common but type 2 DM is also being increasingly diagnosed due to the obesity epidemic. Apart from Type 1 and Type 2 DM there are a large number syndromes associated with DM. Several rare syndromes have been described which are associated with glucose intolerance and or DM. These syndromes include Wolfram, Walcott-Rallison, Alström, Bardet-Biedl and the Thiamine responsive megaloblastic anaemia syndromes. Unravelling the molecular mechanisms of DM in these rare syndromes has provided unique insights into glucose physiology.

As part of a European Network we have identified a unique cohort of patients with complex syndromes related to DM. The genetic mechanism/s that lead to DM in these patients are currently unknown. The aim of this project will be to apply the latest cutting edge techniques in genomics (exome and whole genome sequencing) to try and understand the genetic and molecular basis of the DM in these unique patients. Understanding the molecular mechanisms of DM in this patient cohort will provide fundamental novel insights into normal glucose and insulin physiology and potentially help in developing novel therapies for these patients. Understanding novel mechanisms of disease will help in developing therapeutic strategies.

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