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Intensive Type 1 Diabetes Therapy Lowers Kidney Failure Risk by 50 Percent

Nov 18, 2011

Intensive therapy for type 1 diabetes mellitus lowers the long-term risk for impaired glomerular filtration rate (GFR).

Ian de Boer, MD, MS, assistant professor of medicine in the division of nephrology at the University of Washington in Seattle, stated that, compared with conventional therapy, intensive type 1 diabetes therapy halved the risk for impaired GFR over a median follow-up of 22 years. Early intensive therapy appears to have a protective “memory effect” on the kidney.

The study consisted of an intervention trial, the Diabetes Control and Complications Trial (DCCT), and a follow-up observational trial, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. DCCT randomly assigned 1441 individuals with type 1 diabetes to intensive diabetes therapy (n = 711), with 3 or more insulin injections per day and a target of near-normal glucose concentrations, or to conventional diabetes therapy (n = 730) with 1 or 2 injections per day and a target of preventing hyperglycemic symptoms, for 6.5 years. Then 1375 of the participants were followed in the EDIC study; there were approximately equal numbers in the 2 groups.

“The DCCT/EDIC study had phenomenal retention throughout its course, with 85% of participants completing the EDIC year 16 visit, on average, 22 years after baseline,” Dr. de Boer said at a news conference.

Throughout the course of the studies, the intensive and conventional treatment groups were well matched demographically. At the beginning of DCCT, people in both groups had an average age of 27 years (range, 13 to 39 years) and a diabetes duration of 6 years. At initiation, no subject was taking an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker, but by year 16 of EDIC, 53% to 57% of the 2 groups were taking these drugs. Blood pressures remained in the normal range throughout the course of both studies in both groups.

The studies incorporated annual measurements of serum creatinine levels. Over the course of the 2 studies, the investigators determined the long-term effects of intensive therapy on the risk for impairment of the GFR, which was defined as an incident estimated GFR of less than 60 mL/min per 1.73 m² at 2 consecutive study visits.

In DCCT, the primary prevention cohort (n = 711) had diabetes for 1 to 5 years, an albumin excretion rate below 40 mg/day, and no retinopathy; the secondary prevention cohort (n = 730) had diabetes for 1 to 15 years, an albumin excretion rate below 200 mg/day, and at least 1 retinal microaneurysm.

During DCCT, mean glycated hemoglobin (A1c) in the intensive group was 7.3% and in the conventional group was 9.1%. In EDIC years 1 through 16, mean hemoglobin A1c was near 8% in each treatment group, and there was no clinically or statistically significant difference.

Over the 22 years of the 2 studies, 24 individuals in the intensive group developed impaired GFR, as did 46 in the conventional group, resulting in a risk reduction of 50% with intensive therapy (95% confidence interval,18 to 69; P = .006). “It is important to notice the time of these events. Only 4 of 70 occurred during DCCT itself, and 66 of 70 occurred during EDIC study follow-up. You can see that almost all events occurred more than 10 years after randomization,” Dr. de Boer said.

Furthermore, the cumulative incidence of impaired GFR was 5.5% with conventional therapy and 2.0% with intensive therapy, which is an absolute risk reduction of 3.3% and a number needed to treat of 29. Eight participants in the intensive group and 16 in the conventional group developed end-stage kidney disease.

Initially, the intensive group had greater reductions in GFR. In DCCT, intensive therapy was associated with a drop in the mean estimated GFR of 1.7 mL/min per 1.73 m², compared with conventional therapy. However, during EDIC, intensive therapy was associated with a slower rate of decline in the estimated GFR, and an increase in estimated GFR over conventional therapy of 2.5 mL/min per 1.73 m² (P < .001 for both).

The beneficial effect of intensive therapy on the risk for impaired GFR disappeared after adjustment for hemoglobin A1c levels and albumin excretion rates.

Dr. de Boer concluded that “intensive diabetes therapy applied early in the disease course has long-lasting kidney benefits. After combining these data with previous reports that DCCT intensive therapy reduces risks of retinopathy, neuropathy, albuminuria, and cardiovascular disease, these results support current recommendations to target hemoglobin A1c in the clinical care of people with type 1 diabetes.” However, he explained that there is no evidence upon which to extrapolate the results from this study to people with type 2 diabetes.

N Engl J Med. Published online November 12, 2011. Kidney Week 2011: American Society of Nephrology 44th Annual Meeting. Presented November 12, 2011.