Patients with type 2 diabetes may carry a DNA mutation whose identification would allow more precise management. The results of a LabEx E.G.I.D. (European Genomic Institute for Diabetes), published in Nature Metabolism, pave the way for clinical trials for personalized treatments.
About 5 million people in France have type 2 diabetes. This number is expected to increase, along with the figures for obesity, sedentary lifestyle and the aging of the population. However, current multi-drug therapies do not prevent the occurrence of degenerative complications.
Inheritance plays a major role (around 70%) in the development of type 2 diabetes, interacting with environmental risk factors. While “actionable” genes (allowing the personalization of treatments) have been identified for monogenic diabetes (less than 1% of cases), the hypothesis of genetic mutations allowing the optimization of treatments for the 99% of patients apparently suffering. of non-monogenic type 2 diabetes still remained unanswered.
In order to test this hypothesis, the Lille and London team of Dr Amélie Bonnefond (University of Lille / CNRS / Inserm / CHU de Lille / Institut Pasteur de Lille / Imperial College London) and Professor Philippe Froguel (University of Lille / CNRS / Inserm / Lille University Hospital / Institut Pasteur de Lille / Imperial College London), analyzed the genomes of a panel of 74,629 individuals from French, English and American studies. These results revealed that more than 2% of patients with type 2 diabetes in mature adults, ie 100,000 people in France, carried mutations in actionable genes linked to monogenic diabetes. More specifically, the gene encoding glucokinase (the first gene for monogenic diabetes identified in 1992 by the Lille team), but also the HNF4A, KCNJ11, HNF1B and ABCC8 genes.
It has already been proven that familial diabetes linked to glucokinase only very rarely gets complicated. However, these patients undergo heavy and restrictive treatments, such as insulin injections which could be stopped or reduced. For carriers of the other actionable genes, inexpensive and existing non-insulin treatments would be more effective. The results of this new Lille study will ultimately allow a finer mesh in the diagnosis and prevent the patients concerned from treatments that are not very effective because they do not target the cause of diabetes.
As personalized diabetes medicine is the main objective of the Lille National Center for Precision Medicine PreciDIAB, these promising results will make it possible to launch intervention research projects for these patients carrying mutations in the actionable genes of monogenic diabetes.
Pathogenic variants in actionable MODY genes associated with type 2 diabetes.
Amélie Bonnefond, Mathilde Boissel, Alexandre Bolze, Emmanuelle Durand, Bénédicte Toussaint, Emmanuel Vaillant, Stefan Gaget, Franck De Graeve, Aurélie Dechaume, Frédéric Allegaert, David Le Guilcher, Loïc Yengo, Véronique Dhennin, Jean-Michel Borys, James T. Lu , Elizabeth T. Cirulli, Gai Elhanan, Ronan Roussel, Beverley Balkau, Michel Marre, Sylvia Franc, Guillaume Charpentier, Martine Vaxillaire, Mickaël Canouil, Nicole L. Washington, Joseph J. Grzymski, Philippe Froguel.