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Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality

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Orchard, Trevor J., Nathan, David M., Zinman, Bernard, Cleary, Patricia, Brillon, David, Backlund, Jye-Yu C., Lachin, John M.·2015·JAMA
DOI 10.1001/jama.2014.16107PMC PMC4306335
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Abstract

IMPORTANCE: Whether mortality in type 1 diabetes mellitus is affected following intensive glycemic therapy has not been established. OBJECTIVE: To determine whether mortality differed between the original intensive and conventional treatment groups in the long-term follow-up of the Diabetes Control and Complications Trial (DCCT) cohort. DESIGN, SETTING, AND PARTICIPANTS: After the DCCT (1983-1993) ended, participants were followed up in a multisite (27 US and Canadian academic clinical centers) observational study (Epidemiology of Diabetes Control and Complications [EDIC]) until December 31, 2012. Participants were 1441 healthy volunteers with diabetes mellitus who, at baseline, were 13 to 39 years of age with 1 to 15 years of diabetes duration and no or early microvascular complications, and without hypertension, preexisting cardiovascular disease, or other potentially life-threatening disease. INTERVENTIONS AND EXPOSURES: During the clinical trial, participants were randomly assigned to receive intensive therapy (n = 711) aimed at achieving glycemia as close to the nondiabetic range as safely possible, or conventional therapy (n = 730) with the goal of avoiding symptomatic hypoglycemia and hyperglycemia. At the end of the DCCT, after a mean of 6.5 years, intensive therapy was taught and recommended to all participants and diabetes care was returned to personal physicians. MAIN OUTCOMES AND MEASURES: Total and cause-specific mortality was assessed through annual contact with family and friends and through records over 27 years' mean follow-up. RESULTS: Vital status was ascertained for 1429 (99.2%) participants. There were 107 deaths, 64 in the conventional and 43 in the intensive group. The absolute risk difference was -109 per 100,000 patient-years (95% CI, -218 to -1), with lower all-cause mortality risk in the intensive therapy group (hazard ratio [HR] = 0.67 [95% CI, 0.46-0.99]; P = .045). Primary causes of death were cardiovascular disease (24 deaths; 22.4%), cancer (21 deaths; 19.6%), acute diabetes complications (19 deaths; 17.8%), and accidents or suicide (18 deaths; 16.8%). Higher levels of glycated hemoglobin (HbA1c) were associated with all-cause mortality (HR = 1.56 [95% CI, 1.35-1.81 per 10% relative increase in HbA1c]; P < .001), as well as the development of albuminuria (HR = 2.20 [95% CI, 1.46-3.31]; P < .001). CONCLUSIONS AND RELEVANCE: After a mean of 27 years' follow-up of patients with type 1 diabetes, 6.5 years of initial intensive diabetes therapy was associated with a modestly lower all-cause mortality rate when compared with conventional therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00360815 and NCT00360893.

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  • In the DCCT cohort, there was a significant reduction in CV outcomes (42%), nonfatal myocardial infarct (MI), stroke and CV death (57%), as well as all-cause mortality (33%) in previously intensively treated participants compared with those who were previously in the standard arm.

    “In the DCCT cohort, there was a significant reduction in CV outcomes (42%), nonfatal myocardial infarct (MI), stroke and CV death (57%), as well as all-cause mortality (33%) in previously intensively treated participants compared with those who were previously in the standard arm (17)(18)(19).”

    From Targets for Glycemic Control (2018) · cites this paper as [18]

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Authors
Orchard, T. J., Nathan, D. M., Zinman, B., Cleary, P., Brillon, D., Backlund, J.-Y. C., & Lachin, J. M.
Affiliations
  • University of Pittsburgh (US)
  • Harvard University (US)
  • Mount Sinai Hospital (CA)
  • George Washington University (US)
  • Cornell University (US)
Corresponding author
Orchard, Trevor J.
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2015-01-06
Volume
313
Issue
1
Pages
45
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2014.16107
PMC
PMC4306335
OpenAlex
W2006165608
Cited by
437
References
33
Citations by year
2026: 7 · 2025: 16 · 2024: 20 · 2023: 27 · 2022: 32 · 2021: 45 · 2020: 35 · 2019: 45 · 2018: 46 · 2017: 56 · 2016: 55 · 2015: 53
FWCI
60.70
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5u01dk094157-13, UL1TR000142)
  • National Institute of Diabetes and Digestive and Kidney Diseases (U01DK094176, U01-DK094157)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Education
Keywords
type 1 diabetes, tight glycemic control, long-term mortality, Diabetes Control and Complications Trial, EDIC, cardiovascular mortality, cancer mortality, diabetes complications, glycemic variability, HbA1c, mortality risk reduction, cause-specific mortality, young adults with diabetes
MeSH terms
Adolescent, Adult, Aged, Blood Glucose, Cardiovascular Diseases, Cause of Death, Diabetes Mellitus, Type 1, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Hyperglycemia, Hypoglycemia, Hypoglycemic Agents, Male, Middle Aged, Neoplasms, Suicide, Young Adult

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