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Cited by 310Diabetes Management and ResearchHeart Rate Variability and Autonomic ControlDiabetes, Cardiovascular Risks, and Lipoproteins

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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Pop-Busui, Rodica, Low, Phillip A., Waberski, Barbara H., Martin, Catherine L., Albers, James W., Feldman, Eva L., Sommer, Catherine, Cleary, Patricia A. +2 more·2009·Circulation
DOI 10.1161/circulationaha.108.837369PMC PMC2757005
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Abstract

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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Crossref · 10.1161/circulationaha.108.837369

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  • Early detection of CAN may enable tailored interventions that prevent progression and reduce risks of CVD, arrhythmias, myocardial dysfunction leading to CHF, CKD, and all-cause mortality.

    “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]

    The Discussion’s “Clinical Impact of the Paper” section (page unavailable) links CAN to arrhythmias and sudden death and recommends early intensive treatment of type 1 diabetes to protect against diabetic complications. The Discussion also links CAN to cardiovascular events and mortality. It does not establish that early detection enables tailored interventions, or link CAN to myocardial dysfunction leading to CHF or to CKD. (LLM, conf=0.86)

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  • The prevalence of and risk factors for ECG-derived CAN were similar to previously reported estimates for CAN defined by gold-standard cardiovascular autonomic reflex tests (CARTs).

    “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]

    The Methods and Results (pages unavailable in our copy) describe CAN assessed through paced-breathing R-R variation, the Valsalva maneuver and postural blood-pressure changes, and report its prevalence. The Discussion identifies factors associated with CAN, including glycemic control, disease duration, age and blood pressure. The paper does not assess CAN from a standard resting ECG or compare its prevalence and risk factors with ECG-derived estimates, so the claimed similarity is not established by this source. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Intensive glucose control applied early in the course of type 1 diabetes significantly reduces the risk of developing CAN.

    “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].”

    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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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)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2009-06-09
Volume
119
Issue
22
Pages
2886-2893
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.108.837369
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
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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