title: The impact of the angiotensin-converting enzyme insertion/deletion polymorphism on severe hypoglycemia in Type 2 diabetes.
abstract: The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) is associated with altered serum ACE activity. Raised ACE levels and the ACE DD genotype are associated with a 3.2 to 6.8-fold increased risk of severe hypoglycemia in type 1 diabetes. This relationship has not been assessed in type 2 diabetes. We aimed to test for association of the ACE I/D polymorphism with severe hypoglycemia in type 2 diabetes. Patients with type 2 diabetes (n = 308), treated with insulin (n = 124) or sulphonylureas (n = 184), were classified according to whether or not they had previously experienced severe hypoglycemia. Samples of DNA were genotyped for the ACE I/D polymorphism using two alternative polymerase chain reactions to prevent mistyping due to preferential amplification of the D allele. Overall, 12% of patients had previously experienced one or more episodes of severe hypoglycemia. This proportion did not differ between genotype groups (odds ratio (95% confidence limits) for carriers of D allele relative to II homozygotes: 0.79 (0.35-1.78)). This study found no evidence for association of the ACE I/D polymorphism with severe hypoglycemia frequency in patients with type 2 diabetes. However, we cannot rule out a smaller effect (odds ratio </= 1.78). Our results suggest that any effect of ACE genotype on severe hypoglycemia risk in type 2 patients is likely to be smaller than that seen in type 1 diabetes. We recommend future larger-scale studies.
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Freathy
authors.forename: Kathryn F
authors.initials: KF
authors.lastname: Lonnen
authors.forename: Anna M
authors.initials: AM
authors.lastname: Steele
authors.forename: Jayne A L
authors.initials: JA
authors.lastname: Minton
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Macleod