Nice, France – Diabetes is the perfect example of a chronic disease that results from the interaction between genes and the environment. But until today, genetic work has been disappointing: impossible, for example, to predict the development of type 2 diabetes when more than 200 genetic variants associated with the most common form of diabetes have been discovered. On the occasion of the annual congress of the Francophone Diabetes Society (SFD), its president, the Pr Jean-Francois Gautier (endocrinologist, Lariboisière Hospital, Paris) however recalled the interest, still relevant, of genetics. Whether for type 2 diabetes or rare forms of diabetes, better understanding the etiology of diabetes through genetics would make it possible to propose an adequate treatment, argued the specialist during a press conference.
Arguments in favor of genetic research
Jean-François Gautier recalled that more than 250 genetic variants were known to be associated with type 2 diabetes but that taken together, they explain less than 20% of the heritability of T2DM. If these genetic anomalies therefore do not make it possible to effectively predict the development of T2DM, finding others would make it possible to stratify patients – who represent more than 5% of the French population – according to their genetic profile. The subgroups would group the patients according to certain commonalities (early implementation of insulin treatment, high risk of complications, significant insulin resistance).
The increase in the prevalence of atypical forms of diabetes is another element in favor of continuing work aimed at providing the clinician with genetic data that can guide diagnosis. In fact, the diabetologist must deal more and more often with atypical forms of diabetes “which occur young with atypia on the circumstance of discovery, on the appearance of complications or even the need for very early insulin treatment” .
Well-identified etiological forms, others not
There are well-defined etiological forms of diabetes such as T1D, identified monogenic diabetes (MODY), pancreatic diabetes or diabetes secondary to endocrinopathy (Cushing, acromegaly). Their respective diagnostic markers are the dosage of antibodies, the presence of a known genetic variant, pancreatic imaging and hormonal dosage.
“When we ask for a search for monogenic diabetes for a young patient with diabetes without antibodies, in 50 to 80% of cases we do not find a variant” indicates Professor Gautier who continues “it is then a question of unidentified monogenic diabetes (MODYx)”. They are part of the forms of diabetes that are still poorly identified due to the lack of a diagnostic marker, such as T2D, T1B (T1B without antibodies), ketotic T2D, i.e. which decompensates easily without a precipitation factor, or diabetes revealed by drugs (immunotherapy and fulminant diabetes, neuroleptic and ketotic DT2, cortisone and DT2).
Finally, is it important to have the etiological diagnosis? “Yes, because the treatment depends on it,” replies the president of the SFD. DT1A, DT1B and fulminant diabetes are treated with insulin. On the other hand, hypoglycaemics are prescribed in ketotic T2DM, sulfonamides for the HNF1A-MODY3 and MODY1 forms and high doses of sulfonamides for neonatal diabetes (ABCC8 and KCNJ11) for example.
GlucoGEN, the future?
Today, genetic research, which is not reimbursed, is not very accessible because there are few genomic platforms in France. The time required to obtain results largely exceeds twelve months. But things could change…
“Diabetes is at the heart of the France Genomic Medicine Plan 2025” says Professor Gautier. The national GlucoGEN protocol, presented at the congress, should begin next September. “This protocol aims to show the interest of whole genome sequencing and multidisciplinary consultation meetings (geneticist, diabetologist) for the diagnosis and management of atypical diabetes” he explains.
More than 1000 patients concerned, spread over about fifteen centers, will be able to benefit from a genomic analysis. The protocol is as follows: either the request for genetic research follows the usual course, or the doctors use the new genomic platforms, whose rendering times depend on the number of genes sequenced. If the sequencing of the first 20 most frequently involved genes does not yield results, the first 70 genes are sequenced. In case of absence of result, there is the sequencing of the whole genome.
“This is an important project because, at the end of this project, we will see if the primary health insurance fund decides to take charge of genetic research to unravel the etiology of atypical diabetes. concludes, optimistic, Professor Jean-François Gautier.
Follow Medscape in French on Twitter.
Follow theheart.org |Medscape Cardiology on Twitter.
–
