The 5'VNTR proinsulin gene (INS) polymorphism and the functional reserve of beta cells in the intravenous glucose tolerance test

Introduction: Proinsulin 5'VNTR polymorphism determines susceptibility to type 1 diabetes (T1DM). The authors tested whether it affects intravenous glucose tolerance test (IVGTT) results. Aim of the study: To evaluate a possible relationship between 5'VNTR proinsulin gene (INS) polymorphism and glucose, insulin and C-peptide levels during IVGTT among siblings of childen suffering from T1DM. Material and methods: Fourteen patients - siblings of children with type 1 diabetes, positive for at least one autoantibody, underwent IVGTT with glucose, insulin and C-peptide concentrations measurement. Results: Mean age of patients equaled 10.71+/-4.15 years. Eight individuals were homozygous for class I/I and six were class III/I heterozygotes. No significant differences in blood glucose levels during the IVGTT were observed (p=0.67). However, lower insulin (p=0.03) and C-peptide (p=0.01) levels were observed in I/I homozygotes in post-challenge timepoints. No significant differences were observed in baseline fasting insulin, glucose and C-peptide levels. Conclusions: The class III allele in the 5'VNTR promoter region of INS is associated with a greater functional reserve of beta cells in response to a direct hyperglycemic stimulus in individuals with a familial background of T1DM.