TY - JOUR

T1 - Hypoglycemia, S-ACE and ACE genotypes in a Danish nationwide population of children and adolescents with type 1 diabetes

AU - Johannesen, Jesper

AU - Svensson, Jannet

AU - Bergholdt, Regine

AU - Eising, Stefanie

AU - Gramstrup, Hanne

AU - Frandsen, Erik

AU - Dick-Nielsen, Jens

AU - Hansen, Lars

AU - Pociot, Flemming

AU - Mortensen, Henrik B

AU - Danish Society for Diabetes in Childhood and Adolescence

N1 - © 2010 John Wiley & Sons A/S.

PY - 2011/3

Y1 - 2011/3

N2 - 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.

AB - 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.

KW - Adolescent

KW - Age of Onset

KW - Child

KW - Cohort Studies

KW - Denmark

KW - Diabetes Mellitus, Type 1

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetics, Population

KW - Genotype

KW - Humans

KW - Hypoglycemia

KW - Male

KW - Peptidyl-Dipeptidase A

KW - Registries

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/j.1399-5448.2010.00660.x

DO - 10.1111/j.1399-5448.2010.00660.x

M3 - Journal article

C2 - 20546161

VL - 12

SP - 100

EP - 106

JO - Pediatric Diabetes

JF - Pediatric Diabetes

SN - 1399-543X

IS - 2

ER -