The NIDDK Takes on the Complications of Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

Abstract

In the Diabetes Control and Complications Trial (DCCT) (1983-1993), intensive therapy aimed at near-normal glycemia was compared with conventional therapy in 1,441 adolescent and adult participants with type 1 diabetes (T1D) over a mean follow-up of 6.5 years. The primary DCCT results, reported in 1993, demonstrated the benefits of intensive therapy (mean HbA1c ∼7%) compared with conventional therapy (HbA1c ∼9%) in reducing the risk of development and progression of microvascular complications by 35%-76%. HbA1c <7% was adopted worldwide as the therapeutic target for T1D. Subsequently, the Epidemiology of Diabetes Interventions and Complications (EDIC) study (1994-present) was initiated as the observational follow-up of the DCCT cohort. EDIC has shown that the early beneficial effects of intensive versus conventional therapy on complications persisted for ∼10 years after the convergence of HbA1c levels in the two groups during EDIC-a novel concept termed "metabolic memory." During EDIC, prior intensive therapy was also shown to reduce the risk of severe microvascular complications, cardiovascular disease, mortality, and, recently, of age-related outcomes including cognitive impairment, bone loss, and reduced mobility. The DCCT/EDIC cohort is the most extensively studied T1D cohort in history. The participants have been followed and deeply phenotyped for 95% of their diabetes durations and 65% of their lifespans. Throughout its 40+ years, funded by and in close collaboration with the National Institute of Diabetes and Digestive and Kidney Diseases, DCCT/EDIC has generated results that have guided treatment priorities in T1D and led to improved survival and quality of life for millions of people with T1D worldwide.

Graphical abstract

Figure 1

History of DCCT/EDIC, major goals, and results. Metabolic memory refers to the persistent effect of original interventions on complications despite equalization of HbA_1c, while metabolic amnesia refers to loss of metabolic memory effect. RFA, research funding announcement.

Figure 2

Mean HbA_1c levels with 25th–75th percentiles during DCCT and EDIC, separately for the INT therapy group and CONV therapy group. BG, blood glucose; CSII, continuous subcutaneous insulin infusion (insulin pump) therapy; SMBG, self-monitored blood glucose.

Figure 3

Event-free (survival) probability curves for any-CVD and MACE, separately for the INT therapy group and CONV therapy group.

Figure 4

Relative mortality rate in the combined DCCT/EDIC cohort relative to the age-, sex-, and race-specific risk for the general population as a function of mean HbA_1c during the DCCT and EDIC, separately for male and female participants.