ADA 2010: Diabetic retinopathy reduced by intensive glucose control, but risk of death increases

Five-year data from a seminal study in patients with type 2 diabetes who are at especially high risk of heart disease show that intensive glucose control does slow the progression of microvascular disease, but mortality is increased and there is no benefit on macrovascular complications.

The ACCORD (Action to Control Cardiovascular Risk in Diabetes) study was halted prematurely after 3.5 years when it became apparent that there was an unexpected higher incidence of death connected with the intensive glucose-lowering strategy (target hemoglobin [Hb] A_1c, 1c level before the transition phase was 6.4% in the intensive arm and 7.5% in the standard arm.

ACCORD had 3 separate aims: to test whether intensive lowering of blood glucose (HbA_1c <6%), intensive lowering of systolic blood pressure to less than 120 mm Hg (vs. <140 mm Hg), and treatment of lipids with a combination of a fibrate and simvastatin (vs. simvastatin alone) would lower diabetes complications.

Progression of diabetic retinopathy measured by fundus photography was assessed in approximately 3,000 of the study participants (from each of the treatment arms).

In the intensive glucose-lowering arm compared with the less-intensive arm, as well as in the fibrate-statin arm compared with the statin-monotherapy arm, progression of diabetic retinopathy was slowed, said Emily Chew, MD, of the Clinical Trials Branch of the Division of Epidemiology and Clinical Applications at the National Eye Institute of the National Institutes of Health.

At 4 years, compared with standard blood-glucose control, those in the intensively treated arm had a reduction in progression of diabetic retinopathy by about one-third, from 10.4% to 7.3%. Similarly, compared with simvastatin alone, addition of a fibrate to simvastatin reduced progression of diabetic retinopathy by one-third, from 10.2% to 6.5%.

There was no difference in the incidence of progression between the 2 blood pressure-lowering arms of ACCORD, said Chew.

At 5 years, 1.5 years after the transition to standard glucose lowering for all patients, mortality in the group originally randomized to intensive glucose lowering remained elevated by 19%, reported Hertzel C. Gerstein, MD, professor and director, division of endocrinology and metabolism, McMaster University and Hamilton Health Sciences, Hamilton, Ontario.

The group initially randomized to intensive glucose control had a lower risk of nonfatal myocardial infarction, a trend toward a reduction in the incidence of stroke, and an increase in the rate of cardiovascular death at 5 years, Gerstein said.

“Targeting an A_1c less than 6% is not better than targeting an A_1c of 7% to 7.9% in people with cardiovascular risk factors,” said Gerstein.