There are several mechanisms leading to fasting hyperglycaemia. One of the most subtle drivers of high glucose levels is a heterogenous group of genetic conditions that cause atypical non-autoimmune forms of diabetes.
A team of researchers from the Faculty of Medicine & Surgery at University of Malta, composed of Dr Nikolai Paul Pace, Ms Celine Ann Grech, Ms Barbara Vella, Dr Ruth Caruana and Professor Josanne Vassallo, has applied targeted genetic analysis to identify dominantly-inherited defects in the glucokinase gene, which regulates glucose metabolism and functions as the pancreatic glucose sensor.
In a cohort of 145 non-obese young adults with fasting hyperglycaemia or early onset type 2 diabetes, the authors show that approximately 3 per cent carry glucokinase defects that drive hyperglycaemia.
In the study, the authors describe novel pathogenic variants in glucokinase, define clinical criteria that can be used to identify mutation carriers, and explore the impact of mutations on protein structure and stability.
The results are relevant and new to the local population with a high disease burden, and are part of an ongoing research effort to define the characteristics of atypical non-autoimmune diabetes in the Maltese population.
