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Intensive Diabetes Therapy and Carotid Intima–Media Thickness in Type 1 Diabetes Mellitus
Open accessAbstract
BACKGROUND: Cardiovascular disease causes severe morbidity and mortality in type 1 diabetes, although the specific risk factors and whether chronic hyperglycemia has a role are unknown. We examined the progression of carotid intima-media thickness, a measure of atherosclerosis, in a population with type 1 diabetes. METHODS: As part of the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the long-term follow-up of the Diabetes Control and Complications Trial (DCCT), 1229 patients with type 1 diabetes underwent B-mode ultrasonography of the internal and common carotid arteries in 1994-1996 and again in 1998-2000. We assessed the intima-media thickness in 611 subjects who had been randomly assigned to receive conventional diabetes treatment during the DCCT and in 618 who had been assigned to receive intensive diabetes treatment. RESULTS: At year 1 of the EDIC study, the carotid intima-media thickness was similar to that in an age- and sex-matched nondiabetic population. After six years, the intima-media thickness was significantly greater in the diabetic patients than in the controls. The mean progression of the intima-media thickness was significantly less in the group that had received intensive therapy during the DCCT than in the group that had received conventional therapy (progression of the intima-media thickness of the common carotid artery, 0.032 vs. 0.046 mm; P=0.01; and progression of the combined intima-media thickness of the common and internal carotid arteries, -0.155 vs. 0.007; P=0.02) after adjustment for other risk factors. Progression of carotid intima-media thickness was associated with age, and the EDIC base-line systolic blood pressure, smoking, the ratio of low-density lipoprotein to high-density lipoprotein cholesterol, and urinary albumin excretion rate and with the mean glycosylated hemoglobin value during the mean duration (6.5 years) of the DCCT. CONCLUSIONS: Intensive therapy during the DCCT resulted in decreased progression of intima-media thickness six years after the end of the trial.
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“Intensive glycemic management resulting in lower A1C levels has also been shown to have a beneficial effect on cardiovascular disease (CVD) complications in type 1 diabetes (9,10)”
From Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy (2009) · cites this paper as [9]
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“and Complications study in type 1 diabetic patients (6), the Steno-2 study in type 2 diabetic patients (4), and the STOP-NIDDM trial in patients with impaired glucose tolerance (5) have obtained evidence for such effects.”
BackgroundDiabetes Mellitus and Cardiovascular Disease
Schmidt, A. M. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.310961 · Cited by 195
Diabetic microvascular complications: can patients at risk be identified? A review
Girach, A., Manner, D. H., & Porta, M. (2006) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2006.01175.x · Cited by 175
Advanced Glycation End Products: A Molecular Target for Vascular Complications in Diabetes
Yamagishi, S., Nakamura, N., Suematsu, M., Kaseda, K., & Matsui, T. (2015) · Molecular Medicine · doi:10.2119/molmed.2015.00067 · Cited by 179
Brott, T. G., Halperin, J. L., Abbara, S., Bacharach, J. M., Barr, J. D., Bush, R. L., Cates, C. U., Creager, M. A., Fowler, S. A., Friday, G. H., et al. (2011) · Stroke · doi:10.1161/str.0b013e3182112cc2 · Cited by 173
The emerging challenge in diabetes: The “metabolic memory”
Ceriello, A. (2012) · Vascular Pharmacology · doi:10.1016/j.vph.2012.05.005 · Cited by 177
“Data from EDIC also suggest that the influence of early glycemic control on the progression to macrovascular events may become more evident with longer follow-up (Nathan et al., 2003; Nathan et al., 2005).”
Insulin as an Anti-Inflammatory and Antiatherogenic Modulator
Dandona, P., Chaudhuri, A., Ghanim, H., & Mohanty, P. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.10.038 · Cited by 173
Jacobson, A. M., Ryan, C. M., Cleary, P. A., Waberski, B. H., Weinger, K., Musen, G., & Dahms, W. T. (2010) · Diabetologia · doi:10.1007/s00125-010-1883-9 · Cited by 170
Early onset of subclinical atherosclerosis in young persons with type 1 diabetes
Krantz, J. S., Mack, W. J., Hodis, H. N., Liu, C., Liu, C.-H., & KAUFMAN, F. R. (2004) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2004.06.042 · Cited by 169
Hypothesis: the ‘metabolic memory’, the new challenge of diabetes
Ihnat, M. A., Thorpe, J. E., & Ceriello, A. (2007) · Diabetic Medicine · doi:10.1111/j.1464-5491.2007.02138.x · Cited by 169
Advanced Glycation End Products (AGEs) and Diabetic Vascular Complications
Yamagishi, S., Nakamura, K., & Imaizumi, T. (2005) · Current Diabetes Reviews · doi:10.2174/1573399052952631 · Cited by 164
“Intensive therapy during the DCCT resulted in decreased progression of intima-media thickness six years after the end of the trial as well [5].”
Mechanisms for Oxidative Stress in Diabetic Cardiovascular Disease
Pennathur, S., & Heinecke, J. W. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1595 · Cited by 165
“erosclerosis, 6 years after the end of the trial (100).”
Radial Artery Tonometry Demonstrates Arterial Stiffness in Children With Type 1 Diabetes
Haller, M. J., Samyn, M. M., Nichols, W. W., Brusko, T. M., Wasserfall, C. H., Schwartz, R. F., Atkinson, M. A., Shuster, J. J., Pierce, G. L., & Silverstein, J. H. (2004) · Diabetes Care · doi:10.2337/diacare.27.12.2911 · Cited by 158
“1%), had significantly increased carotid IMT compared with control subjects (18,19).”
BackgroundMadonna, R., & Caterina, R. D. (2011) · Vascular Pharmacology · doi:10.1016/j.vph.2011.03.005 · Cited by 157
“Taken together, these data show that glucose toxicity exerts a major role in microvascular complications, which are more closely temporally related to the onset of hyperglycemia, than macrovascular ones (Lachin et al., 2008; Nathan et al., 2003; UK Prospective Diabetes Study (UKPDS) Group, 1998a).”
BackgroundInfluentialRamasamy, R., Yan, S. F., & Schmidt, A. M. (2012) · Vascular Pharmacology · doi:10.1016/j.vph.2012.06.004 · Cited by 151
Cardiovascular Risk in Type 1 Diabetes Mellitus
Schofield, J. D., Ho, J. H., & Soran, H. (2019) · Diabetes Therapy · doi:10.1007/s13300-019-0612-8 · Cited by 164
Del Prato, S., Felton, A.-M., Munro, N., Nesto, R., Zimmet, P., & Zinman, B. (2005) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2005.00674.x · Cited by 150
Gaps and barriers in the control of blood glucose in people with type 2 diabetes
Blonde, L., Aschner, P. J., Bailey, C. J., Ji, L., Leiter, L. A., Matthaei, S., & Management, O. B. O. T. G. P. F. E. D. (2017) · Diabetes and Vascular Disease Research · doi:10.1177/1479164116679775 · Cited by 160
Atherosclerosis in childhood and adolescent type 1 diabetes: early disease, early treatment?
Dahl‐Jørgensen, K., Larsen, J. R., & Hanssen, K. F. (2005) · Diabetologia · doi:10.1007/s00125-005-1832-1 · Cited by 144
“In patients who had received intensive insulin treatment 6 years previously, thickening had progressed to a lesser extent than in the conventionally treated patients [38].”
Metadata
- Authors
- The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group
- Corresponding author
- The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2003-06-05
- Volume
- 348
- Issue
- 23
- Pages
- 2294-2303
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC2701300
- OpenAlex
- W1667957779
- Cited by
- 815
- References
- 46
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 15 · 2023: 13 · 2022: 7 · 2021: 22 · 2020: 20 · 2019: 26 · 2018: 21 · 2017: 24 · 2016: 21 · 2015: 41 · 2014: 34 · 2013: 37 · 2012: 41
- FWCI
- 39.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- AstraZeneca
- GlaxoSmithKline
- National Institutes of Health (n01dk062204-003)
- Genentech
- National Institute of Diabetes and Digestive and Kidney Diseases (N01 DK062204)
- National Center for Research Resources
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- type 1 diabetes, intensive diabetes therapy, carotid intima-media thickness, atherosclerosis, cardiovascular risk, glycemic control, HbA1c, Diabetes Control and Complications Trial, carotid artery, LDL/HDL ratio, urinary albumin excretion, smoking, systolic blood pressure
- MeSH terms
- Adolescent, Adult, Analysis of Variance, Arteriosclerosis, Blood Glucose, Carotid Artery Diseases, Diabetes Mellitus, Type 1, Female, Follow-Up Studies, Humans, Lipids, Male, Risk Factors, Ultrasonography, Linear Models, Least-Squares Analysis, Case-Control Studies, Randomized Controlled Trials as Topic, Carotid Artery, Common, Tunica Intima, Tunica Media, Disease Progression
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