Collaborative Opportunities with the DCCT/EDIC Study

The Diabetes Control and Complications Trial (DCCT) / Epidemiology of Diabetes Interventions and Complications (EDIC) Study is entering its 21st year. From 1983 to 1989, the DCCT recruited 1441 type 1 diabetic participants. They were randomly assigned to 2 treatment groups, intensive and conventional for an average of 6.5 years of randomized treatment time. The DCCT ended in 1993 after demonstrating conclusively that intensive treatment (mean HbA1c 7.2 percent) reduced the development and progression of diabetic retinopathy, nephropathy and neuropathy, compared to conventional treatment (mean HbA1c 9.0 percent).

In 1994, 96 percent of the living participants enrolled in EDIC for regular observational follow-up of metabolic and complications status, using similar methods as in the DCCT. Diabetes care is obtained from the EDIC participants' own physicians, the HbA1c levels of the former intensive and conventional treatment groups quickly drew together and have averaged 8.1 percent and 8.2 percent respectively during 9 years of EDIC follow-up. Nonetheless, the former intensive treatment group continues to exhibit the same reduction in the risks of diabetic retinopathy, nephropathy and neuropathy, starting from a new baseline status at the beginning of EDIC. A similar benefit of intensive treatment during the DCCT on 2 surrogate measures of CVD, carotid intimal-medial thickness and coronary calcification, first measured during EDIC, has also been revealed. This carry-over effect of prior glycemic exposure on the later course of complications (superimposed on the effect of concurrent glycemic exposure) has been called "metabolic memory" or "metabolic imprinting".

Thus the entire DCCT-EDIC database obtained from type 1 diabetic patients, currently of average age 43 years and diabetes duration 21 years, consists of frequent regular assessments of HbA1c, lipid levels, blood pressure and numerous other proven and putative risk factors for microvascular, neuropathic and macrovascular complications, as well as frequent regular assessment of the complications themselves. In addition, serum and urine samples have been obtained annually since the DCCT baseline and stored frozen at -70° C.

The DCCT/EDIC research group welcomes proposals for collaborative studies from any investigator who believes he/she has a research idea that could utilize some of the stored sample collection and clinical phenotypic data in an ancillary study. The primary objective would be to increase our insight into the pathogenesis of diabetic complications and/or the mechanism of "metabolic memory" or "imprinting"that has been uncovered. The scientific questions to be asked, the specific hypotheses to be tested, the laboratory methods to be employed, and the forms of data analysis will all be jointly developed by the proposing investigator and the DCCT/EDIC research group. Any proposal would receive initial review by the relevant DCCT/EDIC committees. If deemed necessary, independent external scientific review may be arranged by the NIDDK, in addition to any required scientific review by other funding agencies.

After completion of the new measurements, the data will be sent to the DCCT/EDIC data coordinating center, where the previously agreed upon analyses and any other pertinent data analyses will be carried out. Responsibility for presentation, publication and authorship will be determined according to written DCCT/EDIC policies, available on request.

Investigators interested in collaborating with the DCCT/EDIC research group should contact Saul Genuth, chairman of EDIC (phone 216-368-5032, fax 216-368-1485. e-mail smg15@po.cwru.edu), David Nathan, cochairman of EDIC (phone 617-726-2875, fax 617-726-6781, e-mail dnathan@partners.org) or Patricia Cleary, data master of EDIC (phone 301-881-9260, fax 301-881-4471, e-mail cleary@biostat.bsc.gwu.edu).

Investigators may also request access to DCCT/EDIC samples together with phenotypic data already in the public domain (DCCT but not EDIC data is available). We expect to publish a Notice in the NIH guide in Spring 2004 alerting investigators of the availability of the samples. An example of an earlier notice is available at www.nih.gov/grants/guide/notice-files/not99-124.html. Phenotypic data from the DCCT may be obtained by contacting the National Technical Information Service (NTIS), 5285 Port Royal Road, Springfield, VA 22161, phone 888-584-8332.