Does Initiating Intensive Glucose Control Worsen Existing Diabetic Retinopathy?

Lloyd Paul Aiello, MD, PhD; Jerry Cavallerano, OD, PhD

Disclosures

May 02, 2003

Question

Some endocrinologists in Japan state that controlling blood glucose levels too quickly in patients with severe diabetic retinopathy can worsen retinal lesions. Is there any evidence to support this statement?

Response from Lloyd Paul Aiello, MD, PhD and Jerry Cavallerano, OD, PhD

The Diabetes Control and Complications Trial (DCCT) definitively demonstrated that intensive control of blood glucose levels in patients with type 1 diabetes mellitus substantially reduces the risk of onset and progression of diabetic retinopathy.[1,2] In addition, the reduced risks of onset and progression of retinopathy associated with intensive therapy persisted at least 4 years beyond the conclusion of the DCCT, despite near convergence of hemoglobin A1c levels in the intensive-therapy and conventional-therapy groups.[3]

The United Kingdom Prospective Diabetes Study (UKPDS) found similar benefits of intensive blood glucose control for patients with newly diagnosed type 2 diabetes.[4] In the Kumamoto study in Japan of patients with type 2 diabetes who were taking insulin, the benefits of intensive control of blood glucose levels were likewise demonstrated.[5]

The DCCT documented "early worsening" of diabetic retinopathy in the study population.[6] Early worsening of retinopathy was defined as a 3-step or more progression of retinopathy on the severity scale, the development of cotton wool spots and/or intraretinal microvascular abnormalities, and "clinically important retinopathy" if it occurred between baseline and the 12-month follow-up visit. Early worsening of retinopathy occurred in 13.1% of 711 patients assigned to intensive treatment and in 7.6% of 728 patients assigned to conventional treatment. Nevertheless, after 18 months this early worsening in retinopathy reversed, and patients in the intensive-treatment group fared better than those on conventional therapy. Risk factors for early worsening were higher hemoglobin A1c level at baseline and reduction of this level during the first 6 months following randomization. There was no evidence that a gradual reduction in A1c levels reduced the risk of early worsening.

In the DCCT, the long-term benefits of intensive control clearly outweighed the risk of early worsening of retinopathy, and no case of early worsening resulted in serious visual loss. Based on these findings, it is recommended that persons with type 1 or type 2 diabetes initiate intensive therapy as early as possible, and maintain intensive therapy for as long as possible, with the expectation that intensive control of blood glucose levels will reduce the risk of onset and progression of diabetic retinopathy. For patients with elevated hemoglobin A1c levels, careful retinal evaluation, close retinal follow-up, and laser photocoagulation as indicated are important components of care as intensive therapy is initiated.

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