No renal benefits of ACE inhibitor, statin treatment in adolescents with type 1 diabetes
medwireNews: Results of AdDIT show that treatment with an ACE inhibitor, a statin, or both does not protect against the increased albumin excretion that frequently occurs in patients with type 1 diabetes during adolescence.
However, lead study author M Loredana Marcovecchio (University of Cambridge, UK) told medwireNews that it “is too soon to know whether this short-term intervention will reduce long-term complications risk.”
Such a “legacy effect” of a period of tight risk factor control has been observed in studies of adults with diabetes.
“Follow-up of the AdDIT cohort is undergoing to establish the full benefits of statins and ACE inhibitors in relation to long-term complications, and it will continue to inform our future understanding and our options for effective therapies for this vulnerable group of young people with type 1 diabetes,” said Marcovecchio.
The primary outcome of AdDIT (Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial) was patients’ albumin-to-creatinine ratio (ACR), measured on 3 consecutive days every 6 months. The researchers selected this endpoint “because previous longitudinal studies had shown that increases in the albumin-to-creatinine ratio during puberty, below the thresholds for microalbuminuria and macroalbuminuria, were associated with risk markers for cardiovascular disease.”
This is thought to occur as a result of poor glycemic control in this age group. “Predictably, in this population, the mean glycated hemoglobin level increased by approximately 0.5% during the trial period, despite a high rate of insulin-pump therapy (50%),” the team writes.
The 443 trial participants were aged an average of 12.4 years and had an adjusted ACR in the upper third of the more than 4000 patients originally screened for the trial. However, during 2 to 4 years of treatment, changes in the ACR did not significantly differ between patients taking an ACE inhibitor, a statin, both medications, or placebo, the team reports in The New England Journal of Medicine.
Patients receiving an ACE inhibitor took quinapril at a dose of 5 to 10 mg/day and those taking a statin took atorvastatin 10 mg/day.
Despite its lack of effect on ACR, treatment with the ACE inhibitor nearly halved the cumulative incidence of microalbuminuria. This was not considered statistically significant because of the nonsignificant effect on the primary outcome, but the researchers suggest that “it may be of clinical relevance, since it was related to reduced variability in the albumin-to-creatinine ratio.”
Statin therapy resulted in a significant reduction in cholesterol levels, but neither that nor ACE inhibitor treatment influenced changes in patients’ carotid intima-media thickness. ACE inhibitor treatment nonsignificantly lowered systolic blood pressure, and also reduced cystatin C levels, whereas statin therapy slightly reduced levels of C-reactive protein.
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