C-reactive protein (CRP) is closely associated with obesity and cardiovascular disease in both diabetic and nondiabetic populations. In the short term, commonly prescribed antidiabetic agents have different effects on CRP; however, the long-term effects of those agents are unknown.

The Diabetes Control and Complications Trial (DCCT) demonstrated the beneficial effects of intensive versus conventional therapy on the development and progression of microvascular complications of type 1 diabetes. These beneficial effects were almost completely explained by the difference between groups in the levels of HbA1c, which in turn were associated with the risk of these complications. We assessed the association of glucose variability within and between quarterly 7-point glucose profiles with the development and progression of retinopathy, nephropathy, and cardiovascular autonomic neuropathy during the DCCT.

This trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing beta-cells in subjects with new-onset type 1 diabetes.

To evaluate the impact of former intensive versus conventional insulin treatment on neuropathy in Diabetes Control and Complications Trial (DCCT) intensive and conventional treatment subjects with type 1 diabetes 13-14 years after DCCT closeout, during which time the two groups had achieved similar A1C levels.

The Diabetes Control and Complications Trial (DCCT, 1983-1993) showed that intensive therapy (mean HbA1c 7.2%) compared with conventional therapy (mean HbA1c 9.0%) markedly reduced the risks of retinopathy, nephropathy, and neuropathy, and these reductions in complications were entirely attributable, statistically, to the difference in mean HbA1c levels. The DCCT cohort has been followed in the Epidemiology of Diabetes Interventions and Complications (EDIC) study (1994 to date). Early in EDIC, mean HbA1c levels in the former intensively and conventionally treated groups converged. Nevertheless, the beneficial effects of DCCT intensive versus conventional therapy on microvascular complications not only persisted but increased during EDIC. The differences in complications during EDIC were wholly explained, statistically, by differences between groups in HbA1c levels during DCCT. These observations give rise to the concept of metabolic memory. Subsequent similar findings from the UKPDS gave rise to a similar concept, which they called the legacy effect. In this report, we present the evidence to support metabolic memory as both a biological and epidemiological phenomenon and discuss potential underlying mechanisms. We also compare metabolic memory and the legacy effect and conclude that the two are likely biologically similar, with comparable effects on long-term outcomes. The long-term influence of metabolic memory on the risk of micro- and macrovascular complications supports the implementation of intensive therapy, with the goal of maintaining near-normal levels of glycemia, as early and as long as safely possible in order to limit the risk of complications.

OBJECTIVE To describe the beneficial long-term effects of an average of 6.5 years of intensive diabetes therapy (INT) in type 1 diabetes on measures of atherosclerosis, cardiac structure and function, and clinical cardiovascular events observed in the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study. RESEARCH DESIGN AND METHODS The DCCT was a randomized clinical trial of 1,441 participants assigned to receive INT or conventional therapy (CON). It was conducted between 1983-1993 with an average follow-up of 6.5 years. EDIC (1994-present) is an observational follow-up of the DCCT cohort. Cardiovascular events have been recorded throughout. During EDIC common carotid intima-media thickness (IMT) was measured with ultrasound, coronary artery calcification with computed tomography, and cardiac structure and function with cardiac magnetic resonance imaging. RESULTS DCCT INT and lower levels of HbA1c during DCCT/EDIC were associated with thinner carotid IMT, less coronary calcification, and a lower incidence of clinical cardiovascular events including myocardial infarction, stroke, and cardiac death. While there were no significant differences in cardiac structure and function between the former INT and CON groups, they were significantly associated with higher HbA1c during DCCT/EDIC. CONCLUSIONS DCCT INT and the attendant 6.5 years of lower HbA1c had long-term salutary effects on the development and progression of atherosclerosis and cardiovascular disease during the subsequent follow-up during EDIC.

Beta-cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures.

People with type 1 diabetes are at high risk of premature atherosclerosis. Existing evidence suggests that impaired vitamin D metabolism may contribute to the development of atherosclerosis. We tested associations of circulating vitamin D metabolite concentrations with subclinical atherosclerosis among 1,193 participants with type 1 diabetes in the DCCT/EDIC study.

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated the beneficial effects of intensive therapy on atherosclerosis and clinical cardiovascular disease (CVD) outcomes. The current analyses evaluated the relationship between longitudinal changes in insulin dose and CVD risk factors and outcomes.

No abstract available

To evaluate the relationship between long-term glycemia, traditional cardiovascular disease (CVD) risk factors, and ascending aortic stiffness in type 1 diabetes.

The Diabetes Control and Complications Trial (DCCT) and its observational follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) demonstrated the dominant role of glycemia, second only to age, as a risk factor for a first cardiovascular event in type 1 diabetes (T1D). We now investigate the association between established risk factors and the total cardiovascular disease (CVD) burden, including subsequent (i.e., recurrent) events.