The Impact of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on Severe Hypoglycemia in Type 2 Diabetes

Article View

The Review of Diabetic Studies,2006,3,2,76-81.
Published:August 2006
Type:Original Article
Author(s) affiliations:

Rachel M. Freathy, Kathryn F. Lonnen, Anna M. Steele, Jayne A. L. Minton, Timothy M. Frayling, Andrew T. Hattersley and Kenneth M. MacLeod

Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom.


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.