DCCT-EDIC Clinical Trial and Follow-up of Persons with Type 1 Diabetes

The Diabetes Control and Complications Trial (DCCT, 1982-93) and the Epidemiology of Diabetes Interventions and Complications follow-up study (EDIC, 1994-2016) have been ongoing for more than twenty years. After a mean follow-up of approximately 16 years, the DCCT-EDIC cohort of 1,441 Type 1 diabetics had remained remarkably complete with more than 90% of the original cohort being actively followed. Taken together, the DCCT clinical trial and subsequent EDIC longitudinal follow-up provide a uniquely rich source of information on the impact of intensive therapy on glycemia and the its long-term complications for persons with Type 1 diabetes. The DCCT was a multicenter, randomized clinical trial (1, 2) designed to compare intensive with conventional diabetes therapy with regard to their effects on the development and progression of the early complications of Type 1 diabetes. The DCCT trial found that "intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy" in patients with Type 1 diabetes (1). The goal of the EDIC follow-up was to examine the longer term effects of the original DCCT interventions, especially as they apply to late-occurring complications, such as cardiovascular disease and more advanced stages of retinal and renal disease (3). The EDIC study has been remarkably fruitful in discovering the long term "imprinting" effects (metabolic memory) of the previous intensive therapy, and in delineating the interactions among risk factors with regard to microvascular complications (4-6). In addition, EDIC established, for the first time, the role of intensive therapy and chronic glycemia on atherosclerosis (7-9). Note: This study description has been prepared using materials authored by the DCCT-EDIC Data Coordinating Center. DETAILED DESCRIPTION OF STUDY]]>
DCCT Data Collection Forms and Dataset Characteristics (DCCT)Form 21.7: Quarterly visit (Used Sep. '90 to April '93) (DCCT) Form 36: Quality of Life Questionnaire (DCCT)Form 10: Neurobehavioral Assessment (Complete Battery) (DCCT)Form 106: Details of Pregnancy and Outcome (DCCT)FORM 108: PARENTS AND SIBLINGS OF DCCT PATIENT (DCCT)Form 114: Body Composition Measurements (DCCT)Form 122: Patient Experience Questionnaire (DCCT)Form 13: Neurobehavioral Studies Demographic Questionnaire (DCCT)Form 2: Baseline Medical History and Physical Examination (DCCT)Form 20: Notification of Intercurrent Event (DCCT)Forms 21.1-21.6: Quarterly visit (Used through Sep. '90) (DCCT)Form 27: Endpoint Visit Ophthalmic Examination (DCCT)Form 3.3: Annual Medical History and Physical Examination (Used Sep. '90 to Nov. '92) (DCCT)Form 3.4: Close-Out Medical History and Physical Examination (DCCT)Form 37: Nerve Conduction Studies (DCCT)Form 45: Volunteer Understanding Questionnaire (Version A) (DCCT)Form 46: Volunteer Understanding Questionnaire (Version B) (DCCT)Form 48: Family Understanding and Expectation Interview (DCCT)Form 49: Request Behaviors Confidence Questionnaire (DCCT)Form 5: Neurological History and Examination (DCCT)Form 8: Baseline Ophthalmic Examination and Ocular History (DCCT)Form 83: Notification of Hypoglycemic Intercurrent Event (DCCT)Form 88: Neurobehavioral Consensus Rating (DCCT)Form 92: Further Details on Hypoglycemic Event (DCCT)Form 97: GFR Worksheets (DCCT)DCCT/FAM Clustering Data Set: Quasi-Codebook (DCCT)ANALYSIS DOCUMENTATION: The Relationship of Glycemic Exposure (HbA1c) to the Risk of Development and Progression of Retinopathy in the Diabetes Control and Complications Trial (DCCT)ANALYSIS DOCUMENTATION: The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus (DCCT)Analysis Dataset from the Principal DCCT Nephropathy Paper (DCCT)Effects of Intensive Diabetes Therapy on Neuropsychological Function in Adults in the Diabetes Control and Complication Trial (DCCT)ANALYSIS DOCUMENTATION: Effects of Intensive Diabetes Therapy on Neuropsychological Function in Adults in the Diabetes Control and Complications Trial (DCCT)Analysis Data Set from the Principal DCCT Neurology Paper (DCCT)Analysis Dataset from the Principal DCCT Retinopathy Paper (DCCT)ANALYSIS DOCUMENTATION: The Effect of Intensive Diabetes Treatment on the Progression of Diabetic Retinopathy in Insulin-Dependent Diabetes Mellitus (DCCT)Summary of the DCCT/EDIC Study (DCCT)Form 2.3. Annual Medical History and Physical Examination (EDIC)Form 2.4. Annual Medical History and Physical Examination (EDIC)Form 4.2. Current Medication Form (EDIC)Form 4.3. Annual Medical History and Physical Examination (EDIC)Form 4.4. Current Medication Form (EDIC)Form 30.2. Ophthalmic Examination and Visual Acuity (EDIC)Form 30.3. Ophthalmic Examination and Visual Acuity (EDIC)Form 42.2. Notification and Further Details of Severe Hypoglycemia Requiring Assistance (EDIC)Form 42.3. Notification and Further Details of Severe Hypoglycemia Requiring Assistance (EDIC)Form 50.2. Neuropathy Screening Instrument Questionnaire (EDIC)Form 50.3. Neuropathy Screening Instrument Questionnaire (EDIC)Form 60.2. Quality of Life Questionnaire (EDIC)Form 61.2. Health Status Questionnaire 2.0 (EDIC)Form 70.3. Health Care Delivery Questionnaire (EDIC)Form 70.4. Health Care Delivery Questionnaire (EDIC)Form 70.5. Health Care Delivery Questionnaire (EDIC)Form 90.2. Verification of Cardiovascular Event (EDIC)Form 90.3. Verification of Cardiovascular Event (EDIC)Form 90.4. Verification of Cardiovascular EventForm 91.3. Verification of Cerebrovascular Event (EDIC)Form 91.4. Verification of Cardiovascular Event (EDIC)Form 92.2. Verification of Peripheral Vascular Event (EDIC)Form 92.3. Verification of Peripheral Vascular Event (EDIC)Form 92.4. Verification of Peripheral Vascular Event (EDIC)Form 93.2. Verification of DKA Event (EDIC)Form 93.3. Verification of DKA Event (EDIC)Form 93.4. Verification of DKA Event (EDIC)Form 94.2. Verification of Psychiatric Disease Requiring Treatment (EDIC)Form 94.3. Verification of Psychiatric Disease Requiring Treatment (EDIC)Form 94.4. Verification of Psychiatric Disease Requiring Treatment (EDIC)Form 95.2. Verification of Major Accident (EDIC)Form 95.3. Verification of Major Accident (EDIC)Form 95.4. Verification of Major Accident (EDIC)Form 140.2. Notification of Death (EDIC)Form 141.2. Notification of Missed Clinic Visit or Modification of Follow-up Schedule (EDIC)Form 141.3. Notification of Missed Clinic Visit or Modification of Follow-up Schedule (EDIC)Form 142.2. Notification of Patient Transfer or Move (EDIC)Form 144.2. Notification of Transfer to Inactive Status (EDIC)Form 144.3. Notification of Transfer to Inactive Status (EDIC)Form 145.2. Checklist for Tracking Inactive or Recalcitrant Patient (EDIC)Analysis Data Set from the EDIC Eight Year Nephropathy Paper* (EDIC)Analysis Data Set from the EDIC Eight Year Neuropathy Paper (EDIC)Protocol (EDIC)Summary of the DCCT/EDIC Study (EDIC)Form 70.2. Health Care Delivery Questionnaire (EDIC)Form 2.2. Annual Medical History and Physical Examination (EDIC)Form 28: Autonomic Neuropathy Studies (DCCT)Adverse Events and Their Association with Treatment Regimens in the Diabetes Control and Complications Trial (DCCT)ANALYSIS DOCUMENTATION: Adverse Events and their Association with Treatment Regimens in The Diabetes Control and Complications Trial (DCCT)C-peptide test results (DCCT)CBL data (baseline) (DCCT)CBL data (close-out) (DCCT)CBL data (year 1) (DCCT)CBL data (year 2) (DCCT)CBL data (year 3) (DCCT)CBL data (year 4) (DCCT)CBL data (year 5) (DCCT)CBL data (year 6) (DCCT)CBL data (year 7) (DCCT)CBL data (year 8) (DCCT)CBL data (year 9) (DCCT)Diet History (DCCT)ANALYSIS DOCUMENTATION: Clustering of Long-Term Complications in Families with Diabetes in the Diabetes Control and Complications Trial (DCCT)Form 1: Initial Clinic Visit (DCCT)Form 56: Clinic Evaluation of Volunteer's Performance on Behavioral Tasks I (Clinic) (DCCT)Form 57: Clinic Evaluation of Volunteer's Performance on Behavioral Tasks II (Home) (DCCT)Form 47: Availability, Adherence and Expectation Interview (DCCT)Monthly HbA1c values (DCCT)Blood-glucose profiles (DCCT)MANUAL OF OPERATIONS (DCCT)Patient identification (DCCT)Patient status (DCCT)Form 35: Symptom checklist 90. Revised (SCL-90R) (DCCT)Form 128: Health Status Questionnaire (SF-36) (DCCT)Forms 3.1-3.2: Annual Medical History and Physical Examination (Used through Sep. '90) (DCCT)Form 24: Resting Electrocardiogram Grading Form (DCCT)PROTOCOL (Full-Scale Clinical Trial – Phase III) for the Diabetes Control and Complications Trial (DCCT)ANALYSIS DOCUMENTATION: The Effect of Intensive Diabetes Therapy on the Development and Progression of Neuropathy (DCCT)Analysis Data Sets from the Principal DCCT Macrovascular Paper (DCCT)Relationship of Glycemic Exposure (HBA1C) to the Risk of Development and Progression of Retinopathy in the Diabetes Control and Complication Trial. Data Documentation. (DCCT)Dataset Integrity Check: DCCT-EDIC 8-year Neuropathy Analysis Dataset (EDIC)Dataset Integrity Check: DCCT-EDIC Diabetic Nephropathy Analysis File (EDIC)EDIC Data Collection Forms and Dataset Characteristics (EDIC)DCCT Baseline Data Set (DCCT)CHAPTER 1: OBJECTIVES AND DESIGN (DCCT)CHAPTER 2: ADMINISTRATIVE STRUCTURE (DCCT)CHAPTER 3: POLICY (DCCT)CHAPTER 4: RECRUITMENT (DCCT)CHAPTER 5: CLINICAL CENTER PROCEDURES (DCCT)CHAPTER 6: VISIT PROCEDURES (DCCT)CHAPTER 7: INFORMED CONSENT PROCESS (DCCT)CHAPTER 8: ENTRANCE CRITERIA AND RANDOMIZATION PROCEDURES (DCCT)CHAPTER 9: MEDICAL MANAGEMENT PROCEDURES (DCCT)CHAPTER 10: DEFINITIONS AND MANAGEMENT OF INTERCURRENT EVENTS (DCCT)CHAPTER 11: CHANGES IN TREATMENT OR FOLLOW-UP SCHEDULE (DCCT)CHAPTER 12: LABORATORY SPECIMENS (DCCT)CHAPTER 13: CLINIC OPHTHALMOLOGIC PROCEDURES (DCCT)CHAPTER 14: THE CENTRAL OPHTHALMOLOCIC READING UNIT (DCCT)CHAPTER 15: THE CENTRAL BIOCHEMISTRY LABORATORY (DCCT)CHAPTER 16: DIETARY PROCEDURES (DCCT)CHAPTER 17: NEUROLOGICAL PROCEDURES (DCCT)CHAPTER 18: CARDIOVASCULAR PROCEDURES (DCCT)CHAPTER 19: PSYCHOLOGICAL PROCEDURES (DCCT)CHAPTER 20: COMPLIANCE (DCCT)CHAPTER 21: COMPLETION AND MAILING OF FORMS (DCCT)CHAPTER 22: SUPPLIES AND INVENTORY (DCCT)CHAPTER 23: CERTIFICATION PROCEDURES (DCCT)CHAPTER 24: POLICY AND GUIDELINES FOR PATIENT TRANSFERS (DCCT)CHAPTER 25: PROCEDURES TO BE FOLLOWED IN THE EVENT OF A DEATH OF A DCCT VOLUNTEER (DCCT)CHAPTER 26: DCCT OPERATIONS AND TELECOMMUNICATIONS SYSTEM (DCCT)CHAPTER 27: MORBIDITY AND MORTALITY CLASSIFICATION COMMITTEE PROCEDURES (DCCT)CHAPTER 28: BODY COMPOSITION (DCCT)APPENDIX A: DCCT FORMS (DCCT)APPENDIX B: DCCT TEACHING OBJECTIVES (DCCT)ANALYSIS DOCUMENTATION: The Effect of Intensive Therapy on the Development and Progression of Diabetic Nephropathy in the Diabetes Control and Complication Trial (DCCT)In 1997-99 (4-6 years after DCCT closeout) blood samples were collected from 1,063 EDIC participants who agreed to participate as part of an ancillary study of biomarkers for long-term diabetic complications. Of these, E-selectin levels were measured in 752 due to limited available serum. Serum levels of soluble E-selectin (E-Selectin) were determined using a monoclonal antibody as part of a SearchLight Proteome Array (Pierce Biotechnology, Rockford, IL) with ArrayVision software for data analysis. The inter-assay coefficient of variation was 5% and intra-assay coefficient of variation was < 2%. We performed genome-wide association analysis of the mean of the HbA1c measured obtained from subjects during the DCCT to identify loci associated with HbA1c in individuals with type 1 diabetes. We calculated the mean HbA1c for each individual in the Conventional treatment group using the mean of all HbA1c values during DCCT including the eligibility HbA1c. Association analysis was performed using normal scores (2df). We performed genome-wide association analysis of the mean of the HbA1c measured obtained from subjects during the DCCT to identify loci associated with HbA1c in individuals with type 1 diabetes. We calculated the mean HbA1c for each individual in the Intensive treatment group using HbA1c values measured from DCCT year one onwards. Association analysis was performed using normal scores (2df). We performed genome-wide association analysis of the mean of the HbA1c measured obtained from subjects during the DCCT to identify loci associated with HbA1c in individuals with type 1 diabetes. We calculated the mean HbA1c for each individual.using HbA1c values measured from DCCT year one onwards. Since HbA1c differed by treatment group, we included treatment group as a covariate. Association analysis was performed using normal scores (2df).Skin intrinsic fluorescence, excited at 375 nm, detected at 435-655 nm, Kx=0.6, Km=0.2, arbritary units was measured using SCOUT DS (Veralight, NM). Linear regression using additive coding of SNP genotype, including covariates, in 1082 individuals with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study.The major criteria for eligibility included insulin dependence, as evidenced by deficient C-peptide secretion; an age of 13 to 39 years; and the absence of hypertension, hypercholesterolemia, and severe diabetic complications or medical conditions. To be eligible for the primary-prevention cohort, patients were required to have had IDDM for one to five years, to have no retinopathy as detected by seven-field stereoscopic fundus photography, and to have urinary albumin excretion of less than 40 mg per 24 hours. To be eligible for the secondary intervention cohort, the patients were required to have had IDDM for 1 to 15 years, to have very mild-to-moderate nonproliferative retinopathy, and to have urinary albumin excretion of less than 200 mg per 24 hours. (Excerpted from 1993 study report in NEJM, PMID: 8366922.) FURTHER DETAILS ON CRITERIA]]>