Elsevier

The Lancet

Volume 351, Issue 9095, 3 January 1998, Pages 28-31
The Lancet

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

https://doi.org/10.1016/S0140-6736(97)06209-0Get rights and content

Summary

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).

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 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% Cl 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).

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.

Introduction

Retinopathy eventually develops in 70–100% of people with type 1 diabetes (insulin-dependent diabetes mellitus) and remains a common cause of visual impairment and eventual blindness.1, 2, 3 The only intervention that prevents development and slows progression of retinopathy is tight glycaemic control.4 However, this approach is not wholly effective, and other interventions must be sought.

Blood pressure is an important risk factor for the development of retinopathy.5, 6, 7 Antihypertensive therapy, especially inhibitors of angiotensin-converting enzyme (ACE), slow the progression of nephropathy,8, 9 but whether these agents have a beneficial effect on retinopathy is much less clear. Previous randomised controlled trials of these drugs in people with type 1 diabetes either did not collect standardised data on retinopathy status,9 or did not have sufficient power10, 11 to show an effect. We report the retinopathy results from the EUCLID (EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus) study.12

Section snippets

Methods

The EUCLID study was a double-blind, randomised, parallel-design clinical trial of lisinopril, an ACE inhibitor, and placebo in 18 European centres, in 530 patients. Men and women with type 1 diabetes13 aged 20–59 years were recruited if resting blood pressure was 75–90 mm Hg diastolic, and 155 mm Hg or less systolic. Most of the patients were normoalbuminuric (albumin-excretion rate <20 μg/min); 15% were microalbuminuric (albumin-excretion rate 20–200 μg/min).

Trained photographers took retinal

Results

409 of 530 patients had gradable baseline photographs. 121 patients did not have photographs. Therefore, gradable photographs were obtained at baseline and follow-up for 354 (81·6%) of 434 eligible patients (figure 1). The only significant differences in baseline characteristics between patients with and without photograhs were for diastolic blood pressure (81 vs 79 mm Hg in patients with and without photographs; p=0·0001), and distribution of sex (47 vs 37% women of patients with and without

Discussion

We show that lisinopril had beneficial effects on progression of retinopathy. Non-significant benefits have been shown previously with other ACE inhibitors in people with type 110, 11, 19 and type 2 (non-insulin-dependent diabetes mellitus).17

The analyses for retinopathy were included in the EUCLID protocol, but the study was not primarily designed to assess the effects of ACE inhibitors on retinopathy. However, retinal photographs taken by standard methods are an accepted way of assessing

References (26)

  • AK Sjolie et al.

    Retinopathy and vision loss in insulin-dependent diabetes in Europe

    Ophthalmology

    (1997)
  • SS Feman et al.

    Serum angiotensin converting enzyme in diabetic patients

    Am J Med Sci

    (1993)
  • MS Dwyer et al.

    Incidence of diabetic retinopathy and blindness: a population-based study in Rochester, Minnesota

    Diabetes Care

    (1985)
  • R Klein et al.

    The Wisconsin Epidemiologic Study of diabetic retinopathy II prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years

    Arch Ophthalmol

    (1984)
  • The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus

    N Engl J Med

    (1993)
  • R Klein et al.

    Is blood pressure a predictor of the incidence or progression of diabetic retinopathy?

    Arch Intern Med

    (1989)
  • HU Janka et al.

    Risk factors for progression of background retinopathy in long-standing IDDM

    Diabetes

    (1989)
  • A Teuscher et al.

    Incidence of diabetic retinopathy and relationship to baseline plasma glucose and blood pressure

    Diabetes Care

    (1988)
  • EJ Lewis et al.

    The effect of angiotensin converting enzyme inhibition on diabetic nephropathy

    N Engl J Med

    (1993)
  • Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria

    Diabetologia

    (1996)
  • HP Chase et al.

    Angiotensin-converting enzyme inhibitor treatment for young normotensive diabetic subjects: a two-year trial

    Ann Ophthalmol

    (1993)
  • M Larsen et al.

    Protective effect of captopril on the blood-retina barrier in normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy

    Graefes Arch Clin Exp Ophthalmol

    (1990)
  • Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria

    Lancet

    (1997)
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