Intensive glucose control in DM1 and long term risk of impaired GFR

Intensive Diabetes Therapy and GFR in Type 1 Diabetes

The DCCT/EDIC Research Group*

NEJM Nov 12, 2011

Abstract

BACKGROUND

An impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population.

METHODS

In the Diabetes Control and Complications Trial (DCCT), 1441 persons with type 1 diabetes were randomly assigned to 6.5 years of intensive diabetes therapy aimed at achieving near-normal glucose concentrations or to conventional diabetes therapy aimed at preventing hyperglycemic symptoms. Subsequently, 1375 participants were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Serum creatinine levels were measured annually throughout the course of the two studies. The GFR was estimated with the use of the Chronic Kidney Disease Epidemiology Collaboration formula. We analyzed data from the two studies to determine the long-term effects of intensive diabetes therapy on the risk of impairment of the GFR, which was defined as an incident estimated GFR of less than 60 ml per minute per 1.73 m² of body-surface area at two consecutive study visits.

RESULTS

Over a median follow-up period of 22 years in the combined studies, impairment of the GFR developed in 24 participants assigned to intensive therapy and in 46 assigned to conventional therapy (risk reduction with intensive therapy, 50%; 95% confidence interval, 18 to 69; P=0.006). Among these participants, end-stage renal disease developed in 8 participants in the intensive-therapy group and in 16 in the conventional-therapy group. As compared with conventional therapy, intensive therapy was associated with a reduction in the mean estimated GFR of 1.7 ml per minute per 1.73 m² during the DCCT study but during the EDIC study was associated with a slower rate of reduction in the GFR and an increase in the mean estimated GFR of 2.5 ml per minute per 1.73 m² (P<0.001 for both comparisons). The beneficial effect of intensive therapy on the risk of an impaired GFR was fully attenuated after adjustment for glycated hemoglobin levels or albumin excretion rates.

CONCLUSIONS

The long-term risk of an impaired GFR was significantly lower among persons treated early in the course of type 1 diabetes with intensive diabetes therapy than among those treated with conventional diabetes therapy.

Key facts:

• Briefly, intensive therapy consisted of three or more injections of insulin daily or the use of an insulin pump, with the aim of achieving a glycated hemoglobin level of less than 6.05% (which was considered to be the upper limit of the normal range). The goal of conventional therapy was the prevention of symptoms of hyperglycemia and hypoglycemia with the use of one or two injections of insulin daily.

• The mean glycated hemoglobin level during the DCCT (1983 through 1993), time-averaged throughout the study, was 7.3% in the intensive-therapy group and 9.1% in the conventional-therapy group.

• The median follow-up period for the two studies combined was 22 years (interquartile range, 21 to 24). During this time, impairment of the GFR developed in 70 participants, of whom 24 had been assigned to DCCT intensive therapy and 46 to DCCT conventional therapy

• Our data suggest that giving approximately 29 persons with type 1 diabetes intensive diabetes therapy for 6.5 years prevents one case of an impaired GFR over a total follow-up period of 20 years.

• Moreover, along with congruent salutary effects on retinopathy, neuropathy, and cardiovascular disease, these effects reinforce current recommendations to target a glycated hemoglobin level of less than 7% in patients with type 1 diabetes.10,11