Hypoglycemia, S-ACE and ACE genotypes in a Danish nationwide population of children and adolescents with type 1 diabetes

Pediatr Diabetes. 2011 Mar;12(2):100-6. doi: 10.1111/j.1399-5448.2010.00660.x.

Abstract

Objective: High S-ACE levels have been shown to predispose to increased risk of hypoglycemia, however; some inconsistency relates to the risk of the ACE genotype. We investigated the association between S-ACE level at diagnosis and ACE genotype to long-term risk of severe hypoglycemia in more than 1000 children and adolescents with type 1 diabetes being part of the Danish Registry of Childhood diabetes over a 10-yr period.

Research design and methods: The Registry provided annual registration of clinical data, e.g., HbA1c, blood glucose monitoring, insulin type and dosage and acute diabetic complications (hypoglycemia and DKA). A BioBank coupled to the Registry comprised serum for measuring S-ACE levels and DNA for ACE genotyping.

Results: A total of 1037 individuals were included, aged 9.97 yr (SD 3.84). A total of 622 severe hypoglycemic episodes were observed in 270 individuals. Associations to increased risk of hypoglycemia generated from a negative binominal model were long diabetes duration (p < 0.0001) and high S-ACE level (p = 0.0497) when adjusted for ACE genotype. In the stratified analysis, S-ACE and insulin dosage were associated with hypoglycemia in girls (p = 0.026 and 0.028, respectively). An association of S-ACE level to ACE genotype was identified; however, no difference in the frequency of hypoglycemia, diabetes duration or HbA1c was demonstrated between ACE genotypes.

Conclusion: This large nationwide cohort has identified an increased risk for hypoglycemia associated with higher S-ACE level, however only in girls. A strong association was found between ACE genotype and S-ACE levels, but ACE genotype was not related to risk of hypoglycemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Child
  • Cohort Studies
  • Denmark / epidemiology
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genetics, Population
  • Genotype
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / epidemiology*
  • Hypoglycemia / etiology
  • Hypoglycemia / genetics
  • Male
  • Peptidyl-Dipeptidase A / blood*
  • Peptidyl-Dipeptidase A / genetics*
  • Registries

Substances

  • ACE protein, human
  • Peptidyl-Dipeptidase A