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