OBJECTIVEEarly initiation of intensive diabetes therapy aimed at achieving near-normal glycemia reduces the early development of vascular complications in type 1 diabetes. We now assess whether intensive therapy compared with conventional therapy during the Diabetes Control and Complications Trial (DCCT) affected the incidence of cardiovascular disease over 30 years of follow-up.RESEARCH DESIGN AND METHODSThe DCCT randomly assigned 1,441 patients with type 1 diabetes to intensive versus conventional therapy for a mean of 6.5 years, after which 93% were subsequently monitored during the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Cardiovascular disease (nonfatal myocardial infarction and stroke, cardiovascular death, confirmed angina, congestive heart failure, and coronary artery revascularization) was adjudicated using standardized measures.RESULTSDuring 30 years of follow-up in DCCT and EDIC, 149 cardiovascular disease events occurred in 82 former intensive treatment group subjects versus 217 events in 102 former conventional treatment group subjects. Intensive therapy reduced the incidence of any cardiovascular disease by 30% (95% CI 7, 48; P = 0.016), and the incidence of major cardiovascular events (nonfatal myocardial infarction, stroke, or cardiovascular death) by 32% (95% CI −3, 56; P = 0.07). The lower HbA1c levels during the DCCT/EDIC statistically account for all of the observed treatment effect on cardiovascular disease risk. Increased albuminuria was also independently associated with cardiovascular disease risk.CONCLUSIONSIntensive diabetes therapy during the DCCT (6.5 years) has long-term beneficial effects on the incidence of cardiovascular disease in type 1 diabetes that persist for up to 30 years.

Background-Clinical treatment goals of type 1 diabetes mellitus (T1DM) have changed since the Diabetes Control and Complications Trial (DCCT) demonstrated reduced long-term complications with intensive diabetes therapy. There have been few longitudinal studies to describe the clinical course of T1DM in the age of intensive therapy. Our objective was to describe the current-day clinical course of T1DM.

The purpose of this report is to summarize and integrate the findings of the Diabetes Control and Complications Trial (DCCT), a randomized controlled clinical trial, and the succeeding observational follow-up of the DCCT cohort in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, regarding the effects of intensive treatment on the microvascular complications of type 1 diabetes mellitus. The DCCT proved that intensive treatment reduced the risks of retinopathy, nephropathy, and neuropathy by 35% to 90% compared with conventional treatment. The absolute risks of retinopathy and nephropathy were proportional to the mean glycosylated hemoglobin (HbA 1c ) level over the follow-up period preceding each event Intensive treatment was most effective when begun early, before complications were detectable. These risk reductions, achieved at a median HbA 1c level difference of 9

Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near (rs9942471, = 4.5 × 10) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at and, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.

The Diabetes Control and Complications Trial (DCCT) demonstrated that a mean of 6.5 years of intensive therapy aimed at near-normal glucose levels reduced the risk of development and progression of retinopathy by as much as 76% compared with conventional therapy. The Epidemiology of Diabetes Interventions and Complications study (EDIC) observational follow-up showed that the risk of further progression of retinopathy 4 years after the DCCT ended was also greatly reduced in the former intensive group, despite nearly equivalent levels of HbA1c, a phenomenon termed metabolic memory. Metabolic memory was shown to persist through 10 years of follow-up. We now describe the risk of further progression of retinopathy, progression to proliferative diabetic retinopathy, clinically significant macular edema, and the need for intervention (photocoagulation or anti-VEGF) over 18 years of follow-up in EDIC. The cumulative incidence of each retinal outcome continues to be lower in the former intensive group. However, the year-to-year incidence of these outcomes is now similar, owing in large part to a reduction in risk in the former conventional treatment group.