title: Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus.
abstract: 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-level scale (none to proliferative).
  
  
  RESULTS
  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 HbA1c 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 more 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology and Public Health, University College London, UK. nish@public-health.ucl.ac.uk
authors.forename: N
authors.initials: N
authors.lastname: Chaturvedi
authors.forename: A K
authors.initials: AK
authors.lastname: Sjolie
authors.forename: J M
authors.initials: JM
authors.lastname: Stephenson
authors.forename: H
authors.initials: H
authors.lastname: Abrahamian
authors.forename: M
authors.initials: M
authors.lastname: Keipes
authors.forename: A
authors.initials: A
authors.lastname: Castellarin
authors.forename: Z
authors.initials: Z
authors.lastname: Rogulja-Pepeonik
authors.forename: J H
authors.initials: JH
authors.lastname: Fuller
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017706:Lisinopril / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D017706:Lisinopril