Serum ACE Predicts Severe Hypoglycemia in Children and Adolescents With Type 1 Diabetes

Abstract

OBJECTIVE -To investigate whether risk of severe hypoglycemia is related to serum (S) ACE level during intensive treatment in type 1 diabetic children. (1.0), and the HbA 1c year mean was 4.7-10.2% (6.8). HbA 1c , insulin doses, and events of severe hypoglycemia (needing assistance from another person) were prospectively registered at regular visits, scheduled quarterly. S-ACE was determined once. RESEARCH DESIGN AND METHODSRESULTS -Severe hypoglycemia was correlated to S-ACE (r ϭ 0.22, 95% CI 0.01-0.41, P ϭ 0.0093). The square root of severe hypoglycemia was correlated to S-ACE (r ϭ 0.27, 95% CI 0.06 -0.45, P ϭ 0.0093). Patients with S-ACE at the median level or above (n ϭ 44) reported a mean of 3.0 yearly events of severe hypoglycemia compared with 0.5 events in patients with S-ACE lower than the median (n ϭ 42) (P ϭ 0.0079). Of the patients with an S-ACE at the median level or above, 27 (61%) reported severe hypoglycemia, compared with 17 (40%) patients with an S-ACE lower than the median (P ϭ 0.0527). Insulin dose, HbA 1c , age, onset age, duration, C-peptide, and sex did not differ between these two groups. S-ACE was negatively correlated with age (r ϭ Ϫ0.27, 95% CI Ϫ0.46 to 0.07, P ϭ 0.0265) but not with HbA 1c , duration, or blood pressure.CONCLUSIONS -The elevated rate of severe hypoglycemia among patients with higher S-ACE suggests, among other factors, that a genetic determinant for severe hypoglycemia exists. Further evaluation is needed before the clinical usefulness of this test can be elucidated. Diabetes Care 26:274 -278, 2003

The relationship between ACE genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes

“…Our findings are contrary to those reported recently in adult (sample size of 171 and 207 outpatients) [8,21] and paediatric populations (sample size of 86 patients) [20]. In light of this several questions arise.…”

“…Whether there is a relationship between ACE activity in the ACE genotype in children as in adults has not been studied. If the polymorphism is not functionally important in the young, this may explain the discrepancy between our results and those of Nordfeldt [20].…”

“…The overall incidence rate of 14.0 per 100 patientyears is similar to the rate we have reported previously [2,22] and comparable with other studies [1,29,30]. A Swedish study reported an overall incidence rate of 17.0 per 100 patient-years [20], which is slightly higher than our study, and a median age of 12.8 years compared with 10 years in our study.…”

“…Herings et al [9] and Morris et al [10] have shown that the use of ACE inhibitors increased the risk of having a severe hypoglycaemic event in adults, but these studies were retrospective in design and the findings remain controversial [11][12][13][14]. The fact that a small proportion of patients experiences severe hypoglycaemia whereas other patients with similar glycaemic control remain spared indicates that genetic factors may contribute to an increased risk, and studies conducted in Denmark and Sweden have supported this notion [8,20,21]. This study was of a large population-based cohort of type 1 diabetic children followed prospectively for 12 years and in whom the phenotype of hypoglycaemic frequency has been carefully documented.…”

“…The D allele has also been associated with increased risk of hypertension, diabetic renal complications and cardiovascular complications. Some studies have shown an association between ACE and physical performance [17][18][19], and it has been proposed that there may be a similarity in metabolic features between hypoglycaemia and exercise [8,20,21], such that patients with type 1 diabetes and the DD genotype are at increased risk of severe hypoglycaemia compared with those with the II genotype [21].…”