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. 2007 May;50(5):965-71. doi: 10.1007/s00125-007-0613-4. Epub 2007 Feb 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Australia / epidemiology
  • Child
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Female
  • Genotype
  • Humans
  • Hypoglycemia / enzymology
  • Hypoglycemia / epidemiology
  • Hypoglycemia / genetics*
  • Male
  • Peptidyl-Dipeptidase A / genetics*
  • Polymerase Chain Reaction
  • Risk Assessment
  • Seizures / etiology


  • Peptidyl-Dipeptidase A