Endocrine Abstracts

JOINT2564

Myotonic dystrophy type 1 (DM1) is a dominantly inherited multi-system disease caused by expanded CTG repeats in the 3’ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. Similar to other repeat disorders, the expanded trinucleotide repeat is unstable with a tendency to increase repeat size with age. The clinical spectrum ranges from lethal presentations in infancy to mild, late-onset disease. DM1 causes myotonia, muscle weakness and cardiac, lung and cognitive impairment, early onset cataracts and various endocrine disorders including insulin resistance, goiter (Ben Hamou A OJRD 2019) and an unexplained trend to high blood sodium level (Smals AG Neth J Med. 1980). A neurogenic cause was not confirmed (Descloquement K SFE 2008). Mexiletine is known to improve myotonia by blocking muscle sodium channels Nav1.4. In addition, cardiac conduction disorders which represent the 2^nd cause of mortality in DM1 are linked to alterations in MBNL1 causing dysregulation of alternative splicing of the SCN5A gene which encodes voltage-gated sodium channels Nav1.5 (Freyermuth F Nat Comm 2016) and depends on insulin signaling through the PIP3 pathway (Polina I PNAS 2020). In view of recent advances in the knowledge of voltage-gated sodium channels and their link with glucose metabolism, the hypothesis of a relationship between hypernatremia and levels of insulin resistance in DM1 was investigated.

Objective: To compare serum sodium levels, phenotype and genotype between 3 groups of DM1 patients according to their degree of insulin resistance explored in the frame of a University Reference Center of Neuromuscular Diseases.

Methods: Retrospective cross-sectional study in 100 DM1 patients classified into 3 groups: 44 DM1 with normal OGTT, 36 with glucose intolerance and 20 with diabetes after a systematic OGTT except if diabetes was already known. Patients treated with diuretics, SGLT2 inhibitors or cortisone were excluded.

Results: Sex ratio, number of CTG repeats and natremia did not differ between the 3 groups. Median age (P < 0.0001) and BMI (P < 0.05) differed between the 3 groups. Natremia positively correlated with the number of CTG repeats (r = 0.37; P < 0.001). Patients with natremia ≥ 143 mmol/l had more pacemakers, indicating a higher severity of the disease (P < 0.05).

Conclusion: these results suggest that natremia measurement could be an inexpensive marker of cardiac DM1 severity, ultimately poorly correlated with insulin resistance. The relationship with voltage-gated sodium channels needs to be further investigated.