Aims/hypothesis
Genetic factors may account for familial clustering related to diabetes complications. Studies have shown a significant relationship
between the presence of the deletion (D) allele of the gene encoding ACE and risk of severe hypoglycaemia. This large prospective cohort study assesses this relationship
in a large sample of children and adolescents with type 1 diabetes.
Subjects and methods
We studied 585 children and adolescents (mean age 11.9 ± 4 years, 48.4% males). The frequency of severe hypoglycaemia (an
event leading to loss of consciousness or seizure) was prospectively assessed over the 13-year period 1992–2004. Patients
were seen with their parents every 3 months and data recorded at each visit. The ACE gene was detected using PCR.
Results
In our cohort of 585 children, 186 (31.8%) had at least one episode of severe hypoglycaemia, and of these 28.0% had the II genotype, 48.9% had the ID genotype and 23.1% had the DD genotype. This was in agreement with the Hardy–Weinberg proportion. A total of 477 severe hypoglycaemic episodes was recorded
with a total of 3,404 person-years of follow-up, giving a total incidence of 14 per 100 patient-years. No significant increase
in risk for DD genotype (incidence rate ratio = 0.97, 95% CI 0.61–1.55) relative to II genotype was observed.
Conclusions/interpretation
This large prospective study concludes that the presence of the D allele of the ACE gene does not predict a significantly higher risk of severe hypoglycaemia in type 1 diabetic children and adolescents.
Keywords ACE - Angiotensin-converting enzyme -
ACE genotype - Complications - Polymorphism - Severe hypoglycaemia - Type 1 diabetes mellitus