Betacell and endothelial function in subjects with EXT-1 or EXT-2 mutations

A recent Genome Wide Association Study (GWAS) identified novel risk loci for
type 2 diabetes including EXT-2. This gene codes for exostosin, which is
involved in the elongation of heparan sulphate, a glycosaminoglycan present
throughout the human body. Patients with EXT-1 and EXT-2 mutations are
charactized by the HMO (hereditary multiple osteochondroma) syndrome, having
multipe benign epiphysial bone tumors during pre-puberty due to 50% reduction
in heparansulfate synthesis. However, mice with these mutations are
characterized by smaller glycocalyx and fasting hyperglycemia. We are therefore
interered whether human subjects with these mutations are also characterized by
impaired fasting glucose tolerance, which could shed new light on the causes of
type 2 diabetes mellitus.

Assessment of glucose homeostasis and endothelial function and glycocalyx
status in 30 subjects with heterozygous mutations in EXT1 or EXT2 and 30
unaffected related controls.

Case control study.

Glucose tolerance test is a non-invasive intervention and additional blood
sampling. This observational study will help us the role of heparansulfates in
glycocalyx in development of type 2 diabetes mellitus.