The relationship between ACE genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes
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.
Bulsara, M. K., Holman, C. D. J., van Bockxmeer, F. M., Davis, E. A., Gallego, P. H., Beilby, J. P., et al. (2007). The relationship between ACE genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes. Diabetologia, 50(5), 965-971. doi: 10.1007/s00125-007-0613-4