Introduction:
Regulatory function of renin-angiotensin-aldosterone system in glucose metabolism may interfere with metabolic dysregulation associated with the development of diabetic ketoacidosis (DKA) at type 1 diabetes (T1DM) onset with further impact to clinical course of the disease.

Aim:
Our aim was to evaluate the association between general and gender-specific distribution of the insertion/deletion polymorphism of ACE gene (rs4340) and DKA development at T1DM onset in paediatric patients.

Material and methods:
147 children with newly diagnosed autoimmune T1DM from Pomeranian Province (Poland) were qualified to prospective longitudinal study. The ACE rs4340 polymorphism was analysed using polymerase chain reaction – allele specific amplification (ASA-PCR). DKA diagnosis and its severity were evaluated based on the international guidelines. Patients’ follow-up was conducted throughout 24 months with periodic re-evaluation of fasting C-peptide (FCP) and HbA1c level.

Results and discussion:
In study group the ACE rs4340 polymorphism was distributed according to Hardy–Weinberg equilibrium, without any gender-specific allocation of genotypes. A significant lower frequency of DKA development at time of T1DM diagnosis was observed in girls (P = 0.04). In patients with DKA development at T1DM onset we identified significant decrease in percentage of male carriers of ACE rs4340 II genotype and female carriers of ACE rs4340 DD+ID genotypes in comparison to subjects without DKA in anamnesis. Simultaneously in above subgroups unfavourable dynamics of residual β-cell function were observed.

Conclusions:
Modification of gender-specific trends in DKA development at T1DM onset associated with the ACE rs4340 polymorphism and its further impact to clinical course of disease requires further functional studies to development of new additive therapeutic strategies of disease.