The Diabetes Control and Complications Trial (DCCT, 1983-1993) compared intensive therapy aimed at near normal glycemia versus conventional therapy with no specific glucose targets in 1441 subjects with type 1 diabetes (T1DM). In 1993, after a mean follow-up of 6.5 yrs, the study showed conclusively that intensive therapy reduced the risks of retinopathy, nephropathy, and neuropathy by 35-76%, and that hyperglycemia was a primary determinant of complications. We also described potential adverse effects of intensive therapy;assessed its effects on cardiovascular disease (CVD) risk factors, neurocognition and quality of life;and projected the lifetime health-economic impact. DCCT intensive therapy was then adopted world- wide as standard-of-care for T1DM. The Epidemiology of Diabetes Interventions and its Complications (EDIC, 1994-present) is the observational follow-up study of the DCCT cohort, with 95% of those surviving actively participating. Most outcomes are evaluated annually. CVD events and deaths are carefully documented and adjudicated. EDIC has notably discovered that the early beneficial effects of intensive treatment on complications have persisted for over 10 years despite the similar HbA1c levels during EDIC in the two groups, termed metabolic memory. Remarkably, former intensive therapy also greatly reduced the risk of CVD events. DCCT/EDIC collaborators have also conducted numerous ancillary studies, with separate funding, most recently including measurement of cardiac function on cardiac MRI and measurement of biomarkers of oxidative stress and inflammation as determinants of complications. The overarching goals for the next 5 years are to follow at least 90% of the surviving cohort;to describe accurately the study-long effects of glycemia (HbA1c) and other established and putative risk factors on diabetes complications and the metabolic memory effects of prior DCCT intensive therapy;and to expand knowledge regarding T1DM and its complications by supporting collaborations for new research funding applications to maximally utilize the cohort, phenotypic data set, and collected biologic and genetic samples. The specific scientific aims are to 1) evaluate effects of risk factors, biomarkers and glycemia on risk of clinical CVD;2) assess the long-term changes in CVD risk factors;3) describe effects of DCCT intensive versus conventional therapy on mortality;4) evaluate risk factors for severe retinopathy/nephropathy;5) assess effects of diurnal glycemic variation on complications;and 6) conduct eight new research projects involving new measurements and analyses.

Public Health Relevance

Patients with T1DM (1,500,000 in the US) are at risk of microvascular and cardiovascular complications that are a major cause of morbidity, mortality and health care cost. The DCCT/EDIC is continuing to describe the long term benefits of intensive therapy on increasingly more severe manifestations of these complications, and to explore the mechanisms by which hyperglycemia and nonglycemic factors lead to an increased risk of these adverse complications, potentially affording a future lifetime free of complications and normal life expectancy for future generations.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZDK1-GRB-2 (O4))
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Leschek, Ellen W
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Case Western Reserve University
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Writing Group for the DCCT/EDIC Research Group (2016) Coprogression of Cardiovascular Risk Factors in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study. Diabetes Care 39:1621-30
Kim, Catherine; Karvonen-Gutierrez, Carrie; Kong, Shengchun et al. (2016) Antimüllerian hormone among women with and without type 1 diabetes: the Epidemiology of Diabetes Interventions and Complications Study and the Michigan Bone Health and Metabolism Study. Fertil Steril 106:1446-1452
Zhang, Ying; Jenkins, Alicia J; Basu, Arpita et al. (2016) Associations between intensive diabetes therapy and NMR-determined lipoprotein subclass profiles in type 1 diabetes. J Lipid Res 57:310-7
Basu, Arpita; Jenkins, Alicia J; Zhang, Ying et al. (2016) Nuclear magnetic resonance-determined lipoprotein subclasses and carotid intima-media thickness in type 1 diabetes. Atherosclerosis 244:93-100
Kim, Catherine; Bebu, Ionut; Braffett, Barbara et al. (2016) Testosterone and cardiac mass and function in men with type 1 diabetes in the Epidemiology of Diabetes Interventions and Complications Study (EDIC). Clin Endocrinol (Oxf) 84:693-9
Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group (2016) Intensive Diabetes Treatment and Cardiovascular Outcomes in Type 1 Diabetes: The DCCT/EDIC Study 30-Year Follow-up. Diabetes Care 39:686-93
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group (2016) Risk Factors for Cardiovascular Disease in Type 1 Diabetes. Diabetes 65:1370-9
Jaffa, Miran A; Luttrell, Deirdre; Schmaier, Alvin H et al. (2016) Plasma Prekallikrein Is Associated With Carotid Intima-Media Thickness in Type 1 Diabetes. Diabetes 65:498-502
Writing Team for the DCCT/EDIC Research Group; Gubitosi-Klug, Rose A; Sun, Wanjie et al. (2016) Effects of Prior Intensive Insulin Therapy and Risk Factors on Patient-Reported Visual Function Outcomes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Cohort. JAMA Ophthalmol 134:137-45
Hotaling, James M; Sarma, Aruna V; Patel, Darshan P et al. (2016) Cardiovascular Autonomic Neuropathy, Sexual Dysfunction, and Urinary Incontinence in Women With Type 1 Diabetes. Diabetes Care 39:1587-93

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