he Diabetes Control and Complications Trial was launched by the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) in 1981 when requests for proposals were issued for clinical centers and a central Data Coordinating Center. In early 1982 the Biostatistics Center of the George Washington University was awarded the contract to serve as the Coordinating Center with Dr. John M. Lachin as Principal Investigator and Director, and Ms. Patricia Cleary as Co-Director. In addition, 29 clinical centers in the United States and Canada, and 8 central laboratories and units participated in the trial. The Coordinating Center contract spanned the period 1982-1998. The complete study group is listed in the Appendix to the principal publication of study results in the New England Journal of Medicine.

ince the discovery of insulin in 1921, the medical community debated the glucose hypothesis that the marked elevation of blood glucose (hyperglycemia) associated with diabetes mellitus was responsible for the development and progression of the microvascular complications of type 1 or insulin-dependent diabetes: retinopathy leading to blindness, nephropathy leading to end-stage kidney disease, and neuropathy leading to loss of sensation, ulceration and amputation. The DCCT was designed to definitively answer whether a program of intensive therapy aimed at near normal levels of glycemia, when compared to conventional therapy aimed at maintenance of clinical well being, would affect the risk of onset and progression of these complications.

uring the period 1983-1989, 1441 subjects were enrolled in the study, half the subjects assigned at random to intensive therapy and half to conventional therapy. All subjects were scheduled to be followed until the fall of 1993. However, the dramatic beneficial results of the trial lead to its termination one year early. The results were presented at the June 1993 meeting of the American Diabetes Association and the initial principal results paper appeared in the New England Journal of Medicine in September of that year (DCCT, 1993). The risks of the microvascular complications over the average of 6.5 years of follow-up were reduced by 26-63% with intensive versus conventional therapy. Intensive therapy, however, was associated with an excess weight gain of about 1 kg per year greater than that with conventional therapy, and a 3-fold greater risk of episodes of hypoglycemia where patients experience siezures and/or loss of consciousness, compared to conventional therapy (DCCT, 1995a).

ubsequent extensive statistical epidemiologic investigations showed that the risk of development of microvascular complications was principally determined by the lifetime exposure to hyperglycemia (DCCT, 1995b, 1996). However, the risk of hypoglycemia was weakly related to the level of glycemia, and more strongly related to intensive versus conventional therapy (DCCT, 1997). All total, more than 55 papers have been published that present the various methods and results of the DCCT. The complete DCCT bibliography can be obtained below.

he Harvard Health Letter named the DCCT the number one advance in medicine during 1993. In 1994, the DCCT Research Group was awarded the Charles H. Best Medal for distinguished service in the cause for diabetes, named for the co-founder of insulin. The DCCT has been used to set standards of care for diabetes mellitus worldwide (see links below).

s Coordinating Center, the Biostatistics Center participated in all aspects of the design, conduct and analysis of the study. In addition to Dr. Lachin and Ms. Cleary, statisticians who participated in the study included Jye-Yu Backlund, Oliver Bautista, Peter Gilbert, Max Halperin, David Kenny, James Knoke, K.K.Gordon Lan, Shuping Lan, and Desmond Thompson.

fter the close of the DCCT, the NIDDK launched the study of the Epidemiology of Diabetes Interventions and Complications (EDIC), for which the Biostatistics Center also serves as the Data Coordinating Center. Under the EDIC, the original DCCT cohort is being followed to assess the development of significant microvascular disease and the development of cardiovascular and other macrovascular diseases.

References:

The DCCT Research Group (1997). Hypoglycemia in the Diabetes Control and Complications Trial. Diabetes45: 271-286.

The DCCT Research Group (1996). The absence of a glycemic threshold for the development of long-term complication: the perspective of the Diabetes Control and Complications Trial. Diabetes45: 1289-1298.

The DCCT Research Group (1995a). Adverse events and their association with treatment regimens in the Diabetes Control and Complications Trial. Diabetes Care18: 1415-1427.

The DCCT Research Group (1995b). The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes44: 968-983.

The DCCT Research Group (1993). The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The New England Journal of Medicine329: 977-986.

The following are links to additional information about the DCCT

The complete DCCT Bibliography, including links to abstracts of papers that are available on the www.

The National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) Summary of the DCCT results.

The American Diabetes Association (ADA) position statements:

Clinical Practice Recommendations, Implications of the DCCT

Standards of Medical Care for Patients with Diabetes Mellitus

The Message of the DCCT for Children and Adolescents

The American Association of Diabetes Educators (AADE) Position statement on the DCCT.

The DIABETES MONITOR Commentary on the DCCT.

The following are links to DCCT documents and study data

The DCCT Protocol is available in either Adobe PDF format or Microsoft Word format.

DCCT Protocol in Adobe Acrobat format.

DCCT Protocol in Microsoft Word 97 format.

Many materials from the DCCT have been archived with the National Technical Information Service. Each document or data set is accessable by an NTIS accession number To determine the price of each item, go to the NTIS site and then search for the product with that accession number. To order the item over the www, follow the instructions on the NTIS page for that item. The following are the principal study materials that are available:

PB88-116447/AS

DCCT Manual of Diabetes Tests, Terms and Procedures, November 1987.

PB88-116439/AS

DCCT Research Volunteer's Information Handbook, November 1987.

PB93-183382INZ

The DCCT Manual of Operations, final version, May 1993.

PB96-501895INC

The DCCT Data Tape Archives of all raw study data, April 1996.

PB95-504189INC

The DCCT Baseline Data Set, July 1995.

Specific subsets of the DCCT data that formed the basis for the principal DCCT papers, and the documentation of the analyses performed for some of those papers, are also available from the NTIS.

PB95-238937INZ

Main Results Paper, NEJM, 1993: Analysis Documentation

PB97-502033INC

Diabetic Retinopathy Paper, Archives of Ophthalmology, 1995: Data Set

PB97-137640INZ

Diabetic Retinopathy Paper: Analysis Documentation

PB97-501571INC

Diabetic Nephropathy Paper, Kidney International, 1995: Data Set

PB97-137673INZ

Diabetic Nephropathy Paper: Analysis Documentation

PB97-501563INC

Diabetic Neuropathy Paper, Annals of Internal Medicine, 1995: Data Set

PB97-137681INZ

Diabetic Neuropathy Paper: Analysis Documentation

PB97-501605INC

Adverse Events Paper, Diabetes Care, 1995: Data Sets

PB97-137657INZ

Adverse Events Paper: Analysis Documentation

PB97-501597INC

Neurobehavioral Results Paper, Annals of Internal Medicine, 1996: Data Sets

PB97-137699INZ

Neurobehavioral Results Paper: Analysis Documentation

PB97-501589INC

Macrovascular Outcomes Paper, The American Journal of Cardiology, 1995: Data set

PB97-502025INC

Relationship to Glycemic Exposure Paper, Diabetes, 1995: Data Set

PB97-137665INZ

Relationship to Glycemic Exposure Paper: Analysis Documentation

PB98-502503INC

Familial Clustering Paper Diabetes, 1997: Data Set

Pending

Familial Clustering Paper: Analysis documentation

Pending

Economic Evaluation Paper, Journal of the American Medical Association, 1996: Analysis Documentation