Sustained Effect of Intensive Treatment of Type 1 Diabetes Mellitus on Development and Progression of Diabetic Nephropathy: The Epidemiology of Diabetes Interventions and Complications (EDIC) Study

• Published in: JAMA : the journal of the American Medical Association Vol. 290; no. 16; pp. 2159 - 2167
• Main Authors: Steffes, Michael W, Chavers, Blanche M, Molitch, Mark E, Cleary, Patricia A
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 22-10-2003
• Subjects: Adolescent; Adult; Albuminuria - etiology; Associated diseases and complications; Biological and medical sciences; Blood Glucose - metabolism; Blood Pressure; Clinical trials; Creatinine - blood; Diabetes; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 1 - therapy; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - epidemiology; Diabetic Nephropathies - prevention & control; Disease Progression; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epidemiology; Female; Glycated Hemoglobin - metabolism; Humans; Hypertension - etiology; Kidney Function Tests; Male; Medical sciences; Medical treatment; Side effects; Endocrinopathy; Kidney disease; Human; Immunopathology; Intensive care; Urinary system disease; Prognosis; Autoimmune disease; Operation; Epidemiology; Nephropathy; Treatment; Type 1 diabetes; Complication; Public health; Glycemia
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.290.16.2159

CONTEXT The Diabetes Control and Complications Trial (DCCT) demonstrated the
benefits of intensive treatment of diabetes in reducing glycemic levels and
slowing the progression of diabetic nephropathy. The DCCT cohort has been
examined annually for another 8 years as part of the follow-up Epidemiology
of Diabetes Interventions and Complications (EDIC) study. During the EDIC
study, glycemic levels no longer differed substantially between the 2 original
treatment groups. OBJECTIVE To determine the long-term effects of intensive vs conventional diabetes
treatment during the DCCT on kidney function during the EDIC study. DESIGN, SETTING, AND PARTICIPANTS Observational study begun in 1993 (following DCCT closeout) in 28 medical
centers in the United States and Canada. Participants were 1349 (of 1375)
EDIC volunteers who had kidney evaluation at years 7 or 8. MAIN OUTCOME MEASURES Development of microalbuminuria, clinical-grade albuminuria, hypertension,
or increase in serum creatinine level. RESULTS Results were analyzed by intention-to-treat analyses, comparing the
2 original DCCT treatment groups. New cases of microalbuminuria occurred during
the EDIC study in 39 (6.8%) of the participants originally assigned to the
intensive-treatment group vs 87 (15.8%) of those assigned to the conventional-treatment
group, for a 59% (95% confidence interval [CI], 39%-73%) reduction in odds,
adjusted for baseline values, compared with a 59% (95% CI, 36%-74%) reduction
at the end of the DCCT (P<.001 for both comparisons).
New cases of clinical albuminuria occurred in 9 (1.4%) of the participants
in the original intensive-treatment group vs 59 (9.4%) of those in the original
conventional-treatment group, representing an 84% reduction in odds (95% CI,
67%-92%), compared with a reduction of 57% (95% CI, −1% to +81%) at
the end of the DCCT. Fewer cases of hypertension (prevalence at year 8, 29.9%
vs 40.3%; P<.001) developed in the original intensive-treatment
group. Significantly fewer participants reached a serum creatinine level of
2 mg/dL or greater in the intensive-treatment vs the conventional-treatment
group (5 vs 19, P = .004), but there were no differences
in mean log clearance values. Although small numbers of patients required
dialysis and/or transplantation, fewer patients experienced either of these
outcomes in the intensive group (4 vs 7, P = .36). CONCLUSIONS The persistent beneficial effects on albumin excretion and the reduced
incidence of hypertension 7 to 8 years after the end of the DCCT suggest that
previous intensive treatment of diabetes with near-normal glycemia during
the DCCT has an extended benefit in delaying progression of diabetic nephropathy.