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Effects of Prior Intensive Insulin Therapy on Cardiac Autonomic Nervous System Function in Type 1 Diabetes Mellitus: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC)
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Background— The Epidemiology of Diabetes Interventions and Complications (EDIC) study, a prospective observational follow-up of the Diabetes Control and Complications Trial (DCCT) cohort, reported persistent benefit of prior intensive therapy on retinopathy and nephropathy in type 1 diabetes mellitus. We evaluated the effects of prior intensive insulin therapy on the prevalence and incidence of cardiac autonomic neuropathy (CAN) in former DCCT intensive and conventional therapy subjects 13 to 14 years after DCCT closeout. Methods and Results— DCCT autonomic measures (R-R variation with paced breathing, Valsalva ratio, postural blood pressure changes, and autonomic symptoms) were repeated in 1226 EDIC subjects in EDIC year 13/14. Logistic regression models were used to calculate the odds of incident CAN by DCCT treatment group after adjustment for DCCT baseline covariates, duration in the DCCT, and quantitative autonomic measures at DCCT closeout. In EDIC year 13/14, the prevalence of CAN using the DCCT composite definition was significantly lower in the former intensive group versus the former conventional group (28.9% versus 35.2%; P =0.018). Adjusted R-R variation was significantly greater in the former DCCT intensive versus the former conventional group (29.9 versus 25.9; P <0.001). Prior DCCT intensive therapy reduced the risks of incident CAN by 31% (odds ratio, 0.69; 95% confidence interval, 0.51 to 0.93) and of incident abnormal R-R variation by 30% (odds ratio, 0.70; 95% confidence interval, 0.51 to 0.96) in EDIC year 13/14. Conclusions— Although CAN prevalence increased in both groups, the incidence was significantly lower in the former intensive group compared with the former conventional group. The benefits of former intensive therapy extend to measures of CAN up to 14 years after DCCT closeout.
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“Timely detection of CAN may help implementation of tailored interventions to prevent its progression and mitigate the risk of associated complications, including CVD, cardiac arrhythmias, myocardial dysfunction leading to congestive heart failure (CHF), CKD, and all-cause mortality.547,614,617–625”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [624]
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“The prevalence of and risk factors for standard resting ECG-derived CAN were similar to previously reported estimates from CARTs.”
From Cardiovascular autonomic neuropathy defined by indices of heart rate variability is associated with cardiovascular disease: a longitudinal cohort study of participants with type 1 diabetes (2025) · cites this paper as [3]
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“The Diabetes Control and Complications Trial (DCCT) and its observational follow-up study, Epidemiology of Diabetes Interventions and Complications (EDIC), conclusively demonstrated that intensive glucose control applied early in the course of type 1 diabetes (T1D), significantly reduces the risk of developing CAN [2–4].”
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Metadata
- Authors
- Pop-Busui, R., Low, P. A., Waberski, B. H., Martin, C. L., Albers, J. W., Feldman, E. L., Sommer, C., Cleary, P. A., Lachin, J. M., & Herman, W. H.
- Affiliations
- From the University of Michigan, Departments of Internal Medicine, Division of Metabolism, Endocrinology, Diabetes (R.P.-B., C.L.M., W.H.H.), and Neurology (J.W.A., E.L.F.), Ann Arbor; Mayo Clinic, Department of Neurology, Rochester, Minn (P.A.L., C.S.); and The Biostatistics Center, George Washington University, Rockville, Md (B.H.W., P.A.C., J.M.L.).
- Mayo Clinic (US)
- Venue
- Circulation
- Published
- 2009-06-09
- Volume
- 119
- Issue
- 22
- Pages
- 2886-2893
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC2757005
- OpenAlex
- W2088134829
- Cited by
- 310
- References
- 29
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 18 · 2023: 14 · 2022: 22 · 2021: 20 · 2020: 30 · 2019: 14 · 2018: 25 · 2017: 16 · 2016: 18 · 2015: 18 · 2014: 19 · 2013: 26 · 2012: 15
- FWCI
- 13.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01dk062204-003)
- National Institute of Diabetes and Digestive and Kidney Diseases (N01 DK062204, R01DK062218)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 1 diabetes, cardiac autonomic neuropathy, intensive insulin therapy, conventional insulin therapy, Diabetes Control and Complications Trial, Valsalva ratio, postural blood pressure, autonomic function, long-term glycemic control
- MeSH terms
- Adult, Autonomic Nervous System, Blood Glucose, Diabetes Mellitus, Type 1, Diabetic Nephropathies, Diabetic Retinopathy, Female, Follow-Up Studies, Heart, Humans, Insulin, Male, Middle Aged, Incidence, Prevalence
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