Modern-day clinical course of type 1 diabetes mellitus after 30 years' duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983-2005)

Abstract

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.

Methods: An analysis of the cumulative incidence of long-term complications was performed. The DCCT (1983-1993) assigned patients to conventional or intensive therapy. Since 1993, the DCCT has been observational, and intensive therapy was recommended for all patients. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study is an observational study of patients with T1DM from Allegheny County, Pennsylvania. The study population comprised the DCCT T1DM cohort (N = 1441) and a subset of the EDC cohort (n = 161) selected to match DCCT entry criteria. In the DCCT, intensive therapy aimed for a near-normal glycemic level with 3 or more daily insulin injections or an insulin pump. Conventional therapy, with 1 to 2 daily insulin injections, was not designed to achieve specific glycemic targets. Main outcome measures included the incidences of proliferative retinopathy, nephropathy (albumin excretion rate >300 mg/24 h, creatinine level >or=2 mg/dL [to convert to micromoles per liter, multiply by 88.4], or renal replacement), and cardiovascular disease.

Results: After 30 years of diabetes, the cumulative incidences of proliferative retinopathy, nephropathy, and cardiovascular disease were 50%, 25%, and 14%, respectively, in the DCCT conventional treatment group, and 47%, 17%, and 14%, respectively, in the EDC cohort. The DCCT intensive therapy group had substantially lower cumulative incidences (21%, 9%, and 9%) and fewer than 1% became blind, required kidney replacement, or had an amputation because of diabetes during that time.

Conclusion: The frequencies of serious complications in patients with T1DM, especially when treated intensively, are lower than that reported historically.

Trial registration: ClinicalTrials.gov NCT00360815 NCT00360893.

Figure 1

Distribution of hemoglobin A_1c (HbA_1c) values over time in the DCCT/EDIC cohort, with intensive and conventional treatment groups shown separately (A), and the EDC cohort (B). The plot summarizes the distribution of HbA_1c by study period as box plots (showing the 25th to 75th percentiles) superimposed on vertical density histograms (“violin” plots). The median of the distribution is indicated by a horizontal line and the mean by “0.” The P values on the x-axis compare the DCCT intensive and conventional treatment groups. DCCT/EDIC indicates Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT 1983-1993 and EDIC 1994-2005); EDC, Pittsburgh Epidemiology of Diabetes Complications (1986-2006). To convert HbA_1c to proportion of 1, multiply by 0.01.

Figure 2

Estimated cumulative incidences of proliferative retinopathy or worse (A), nephropathy (B), and cardiovascular disease (C) over time. Nephropathy was defined as an albumin excretion rate of 300 mg/24 h or higher, a serum creatinine level of 2 mg/dL or higher, or dialysis or renal transplant. Cardiovascular disease was defined as described in the “Clinical Outcomes” subsection of the “Methods” section. DCCT/EDIC indicates Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications; EDC, Pittsburgh Epidemiology of Diabetes Complications.