Endocrine Abstracts

Background: Spinal muscular atrophy (SMA) is hereditary, degenerative, neuro-muscular disease of lower motor neurone that leads to muscle weakness and atrophy. Several metabolic disturbances such as impaired glucose tolerance (IGT), insulin resistance (IR), hypoglycaemia and dyslipidaemia can be present. Most studies were done in children, with more severe forms of SMA. We aimed to assess body composition, IR, glucose and lipid metabolism in adult patients with SMA type 2 and 3.

Material and methods: We designed a cross sectional study consisting of 29 SMA type 2 and 3 (18 (62.1 %) males and 11 (37.9%) females) of median age 44 (30-51.5) years. Anthropometric measurements were performed. Morning blood samples for total cholesterol, LDL, HDL, TG, ApoB, Lp(a), HbA1c and IGF-1 were collected. Blood glucose and insulin were measured during 75 g oral glucose tolerance test (OGTT). Body mass index (BMI) and HOMA-IR were calculated. Body composition was measured with bioimpedance.

Results: BMI was <30 kg/m2 in 25 (86.2%), 30-35 kg/m² in 3 (10.3%), >35 kg/m² in 1 (3.4%). Increased body fat (women >35%, men >25%) was present in 22 (75.9%) patients. 18 (81.8%) patients with BMI <30 kg/m2 had increased body fat. Normal glucose metabolism was present in 8 (28.6%), isolated IGT in 9 (32.1%), impaired fasting glucose and IGT in 2 (7.1%), diabetes in 9 (32.1%). Fasting hypoglycaemia was recorded in 1 patient (3.6%). Insulin resistance (HOMA-IR>2) was present in 16 (55.2%) patients. Only 1 (3.6%) patient had HbA1c>6.0%. Total cholesterol was increased in 20 (69.0%), LDL in 24 (82.8%), TG in 10 (34.5%), HDL was low in 12 (41.4%). ApoB and Lp(a) were increased in 3 (10.7%) and 8 (28.6%) respectively. IGF-1 correlated with body fat (Spearman’s rho -0.547, P=0.002 and -0.582, P=0.001 respectively).

Conclusions: BMI is not suitable for assessing obesity. Body composition should be measured, as in our population 81.8% of patients with BMI<30 kg/m² had increased body fat. Majority of patients have glucose metabolism abnormalities, almost a third fulfils criteria for diabetes. OGTT should be done in all patients with SMA. In children hypoglycaemia is common and usually asymptomatic. Continuous glucose monitoring could add additional information to hypoglycaemia in adults. The most common dyslipidaemia is increased LDL cholesterol. Emerging treatments such as nusinersen, risdiplam and onamsenogene abeparvovec will change course of the SMA, so interdisciplinary approach with inclusion of endocrinologists and appropriate assessment of cardiometabolic risk factors is necessary.