relationship between ACE genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes

• Published in: Diabetologia 2007-05, Vol.50 (5), p.965-971
• Main Authors: Bulsara, M. K, Holman, C. D. J, van Bockxmeer, F. M, Davis, E. A, Gallego, P. H, Beilby, J. P, Palmer, L. J, Choong, C, Jones, T. W
• Format: Article
• Language: English
• Subjects: ACE; ACE genotype; Adolescent; Australia - epidemiology; Biological and medical sciences; Child; Children & youth; Childrens health; Cohort Studies; complications; Consciousness; Diabetes; Diabetes Mellitus, Type 1 - blood; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fainting; Female; Genotype; Genotype & phenotype; Humans; Hypoglycemia; Hypoglycemia - enzymology; Hypoglycemia - epidemiology; Hypoglycemia - genetics; Male; Medical research; Medical sciences; Metabolism; Parents & parenting; Patients; peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - genetics; Polymerase Chain Reaction; Polymorphism; Risk Assessment; Seizures - etiology; Severe hypoglycaemia; Teenagers; Type 1 diabetes mellitus
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-007-0613-4

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.