Endocrine Abstracts

Introduction: Type 1 diabetes (T1D) and multiple sclerosis (MS) are autoimmune diseases with common immunological mechanisms. Type 1 diabetics have an increased risk of MS. The aim of this work is to report a clinical observation of a partial preservation of β-cell function in a type 1 diabetic patient treated early by Fingolimod for MS.

Observation: A polyuro-polydipsic syndrome and a weight loss of 10 kg led to the diagnosis of T1D (typing HLA DR4/DR3, Anti-GAD and anti-IA2 antibodies positive: 3.7 and 3.2 IU/ml respectively, C-fasting peptide: 0.41 ng/ml and HbA1c: 14%) in a 15-year-old patient treated by a basal-bolus insulin. 4 weeks later, the majoration of old balance disorders and the onset of an epileptic seizure (without hypoglycemia), revealed a relapsing-remitting MS, justifying the introduction of an immuno-modulatory treatment by Fingolimod (a sphingosine 1-phosphate receptor modulator which causes a redistribution of T lymphocytes to lymphoid organs, reducing the circulation of auto-aggressive lymphocytes) 11 weeks after discovery of T1D. After 31 months under Fingolimod, glycemic balance is perfect (HbA1c between 5.8 and 7%) with partially preserved insulin reserves (fasting C-peptide around 0.50 ng/ml). According to results of studies on mouse models, Fingolimod preserves β-cell function by modulating the immune response and inhibiting apoptosis (Hosik M Diabetes Metab Res Rev 2013). At 33 months post-diagnosis of T1D, insulin boluses were replaced by Repaglinide at mealtime (before change: fasting C-peptide at 0.5 ng/ml and postprandial at 1.5 ng/ml, glycemia respectively at 1.93 g/l and 2.67 g/l. 4 months after change: fasting C-peptide at 0.51 ng/ml and postprandial at 1.85 ng/ml, glycemia respectively at 1.11 g/l and 1.66 g/l). Metformin has been introduced to reduce insulin resistance in a context of overweight, combined with a GLP-1 analogue. The glycemic balance remains correct with HbA1c between 7 and 8.1% without glycemic fluctuations. The insulin reserves remained stable (12 months after change the fasting C-peptide remains around 0.50 ng/ml).

Discussion: Although slow-type 1 diabetes or a protective effect of the GLP 1 analogue can not be excluded, the early introduction of Fingolimod probably helped to preserve the residual β-cell function, which is consistent with results of work on murine models. This opens new therapeutic hope for management or prevention of T1D as well as the use of Fingolimod in diabetes cell therapy (Bowers J Biomed Mater Res 2017).