Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes

Background Retinopathy commonly occurs in people with type 1 diabetes. Strict glycaemic control can decrease development and progression of retinopathy only partially. Blood pressure is also a risk factor for microvascular complications. Antihypertensive therapy, especially with inhibitors of angiotensin-converting enzyme (ACE), can slow progression of nephropathy, but the effects on retinopathy have not been established. We investigated the effect of lisinopril on retinopathy in type 1 diabetes. Methods As part of a 2-year randomised double-blind placebo-controlled trial, we took retinal photographs at baseline and follow-up (24 months) in patients aged 20-59 in 15 European centres. Patients were not hypertensive, and were normoalbuminuric (85%) or microalbuminuric. Retinopathy was classified from photographs on a five-fever scale (none to proliferative). Findings The proportion of patients with retinopathy at baseline was 65% (117) in the placebo group and 59% (103) in the lisinopril group (p=0.2). Patients on lisinopril had significantly lower HbA(1c) at baseline than those on placebo (6.9% vs 7.3 p=0.05). Retinopathy progressed by at least one level in 21 (13.2%) of 159 patients on lisinopril and 39 (23.4%) of 166 patients on placebo (odds ratio 0.50 [95% CI 0.28-0.89], p=0.02). This 50% reduction was the same when adjusted for centre and glycaemic control (0.55 [0.30-1.03], p=0.06). Lisinopril also decreased progression by two or move grades (0.27 [0.07-1.00], p=0.05), and progression to proliferative retinopathy (0.18 [0.04-0.82], p=0.03). Progression was not associated with albuminuric status at baseline. Treatment reduced retinopathy incidence (0.69 [0.30-1.59], p=0.4). Interpretation Lisinopril may decrease retinopathy progression in non-hypertensive patients who have type 1 diabetes with little or no nephropathy. These findings need to be confirmed before changes to clinical practice can be advocated.