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Serum ACE predicts severe hypoglycemia in children and adolescents with type 1 diabetes
Sam Nordfeldt1, Ulf Samuelsson
1Division of Pediatrics, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping, Sweden. sam.nordfeldt@lio.se
Insights
Higher serum angiotensin-converting enzyme (S-ACE) levels are linked to an increased risk of severe hypoglycemia in children with type 1 diabetes. This finding suggests a potential genetic factor influencing hypoglycemia risk in this population.
Area of Science:
- Endocrinology
- Genetics
- Pediatrics
Background:
- Type 1 diabetes management requires intensive treatment to control blood glucose levels.
- Severe hypoglycemia is a significant complication of intensive diabetes therapy, particularly in children.
- Serum angiotensin-converting enzyme (S-ACE) levels have not been extensively studied in relation to hypoglycemia risk.
Purpose of the Study:
- To determine if serum (S) ACE levels are associated with the risk of severe hypoglycemia in children with type 1 diabetes undergoing intensive treatment.
- To explore potential genetic determinants for severe hypoglycemia in pediatric type 1 diabetes.
Main Methods:
- A prospective cohort study of 86 children with type 1 diabetes receiving intensive treatment.
- Data collected included HbA1c, insulin doses, and events of severe hypoglycemia over a defined period.
- Serum ACE levels were measured once for each patient.
Main Results:
- A significant positive correlation was found between serum ACE levels and the occurrence of severe hypoglycemia (r = 0.22, P = 0.0093).
- Patients with S-ACE levels at or above the median experienced a higher mean number of severe hypoglycemia events annually (3.0 vs. 0.5).
- No significant differences in insulin dose, HbA1c, age, or diabetes duration were observed between groups with high versus low S-ACE levels.
Conclusions:
- Elevated serum ACE levels are associated with an increased rate of severe hypoglycemia in intensively treated children with type 1 diabetes.
- These findings suggest a potential genetic predisposition to severe hypoglycemia.
- Further research is required to validate the clinical utility of S-ACE testing for predicting hypoglycemia risk.
Objective:
To investigate whether risk of severe hypoglycemia is related to serum (S) ACE level during intensive treatment in type 1 diabetic children.
Research Design And Methods:
A cohort of 86 intensively treated type 1 diabetic patients was studied during 1999-2000. In 1999, the age range was 7-19 years (median 12.8), diabetes duration was 1.2-14.7 years (5.3), insulin dose was 0.4-1.7 units x kg(-1) x 24 h(-1) (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.
Results:
Severe hypoglycemia was correlated to S-ACE (r = 0.22, 95% CI 0.01-0.41, P = 0.0093). The square root of severe hypoglycemia was correlated to S-ACE (r = 0.27, 95% CI 0.06-0.45, P = 0.0093). Patients with S-ACE at the median level or above (n = 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 = 42) (P = 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 = 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 = -0.27, 95% CI -0.46 to 0.07, P = 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.