Original Article
Intensive Diabetes Therapy and Glomerular Filtration Rate in Type 1 Diabetes
N Engl J Med 2011; 365:2366-2376December 22, 2011
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. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; DCCT/EDIC ClinicalTrials.gov numbers, NCT00360815 and NCT00360893.)
Supported by contracts with the Division of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Eye Institute, National Institute of Neurological Disorders and Stroke, and the General Clinical Research Centers Program and by funding from the Clinical and Translational Science Awards Program, National Center for Research Resources, and Genentech through a Cooperative Research and Development Agreement with the NIDDK. Additional support for this study came from grants (R01DK087726, R01DK088762, and RC4DK090766) from the NIDDK. Free or discounted supplies or equipment were contributed by Abbott, Animas, Aventis, Bayer, Becton Dickinson, Can Am, Eli Lilly, LifeScan, Medtronic, MiniMed, Omron, OmniPod, Roche, and Sanofi-Aventis. These companies had no role in the design of the study or in the analysis of the data.
Dr. de Boer reports that his institution, the University of Washington, received grants from Abbott Laboratories; Dr. Lachin reports receiving consulting fees from Reata Pharmaceuticals, Eli Lilly, and Novartis Pharmaceuticals; Dr. Molitch reports receiving consulting fees from Abbott Laboratories, Novo Nordisk, and CVS Caremark; Dr. Molitch reports that his institution, Northwestern University, received grants from Sanofi-Aventis and Eli Lilly; and Dr. Steffes reports receiving consulting fees from Pharma Diagnostic. No other potential conflict of interest relevant to this article was reported.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
The members of the writing group for this analysis of the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study (Ian H. de Boer, M.D., University of Washington, Seattle; Wanjie Sun, M.S., Patricia A. Cleary, M.S., and John M. Lachin, Sc.D., The George Washington University, Rockville, MD; Mark E. Molitch, M.D., Northwestern University, Chicago; Michael W. Steffes, M.D., Ph.D., University of Minnesota, Minneapolis; and Bernard Zinman, M.D., Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto) assume responsibility for the content and integrity of this article.
This article (10.1056/NEJMoa1111732) was published on November 12, 2011, at NEJM.org.
We thank the technologists for efficient and accurate completion of the assays used in this study.
Source Information
Address reprint requests to Dr. de Boer at the Kidney Research Institute and Division of Nephrology, University of Washington, Box 359606, 925 9th Ave, Seattle, WA 98104, or at deboer@u.washington.edu.
A complete list of the participants in the DCCT/EDIC research group is provided in the Supplementary Appendix, available at NEJM.org.
Media in This Article
Estimated GFR over Time.
