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


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.


CONCLUSIONS
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.
Johannesen
Jesper
J
Department of Paediatrics, Glostrup University Hospital, DK-2600 Glostrup, Denmark. jesjoh02@glo.regionh.dk
Svensson
Jannet
J
Bergholdt
Regine
R
Eising
Stefanie
S
Gramstrup
Hanne
H
Frandsen
Erik
E
Dick-Nielsen
Jens
J
Hansen
Lars
L
Pociot
Flemming
F
Mortensen
Henrik B
HB
D000293:Adolescent; D017668:Age of Onset; D002648:Child; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000235:genetics*; D012042:Registries
C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A