Mediation of the effect of glycemia on the risk of CVD outcomes in type 1 diabetes: the DCCT/EDIC study
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OBJECTIVE: The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study has demonstrated the major role of hyperglycemia as a risk factor for clinical cardiovascular outcomes in type 1 diabetes (T1D). We assessed whether and to what extent the effect of glycemia is mediated by other established cardiovascular disease (CVD) risk factors. RESEARCH DESIGN AND METHODS: In the DCCT, 1,441 participants were randomized to receive either intensive or conventional diabetes therapy. The EDIC observational follow-up study enrolled 96% of the surviving DCCT cohort with 94% of the survivors still actively participating after more than 27 years of follow-up. Mediation of the effect of glycemia, as captured by HbA1c, on the subsequent CVD risk was quantified using the relative change in the CVD risk associated with HbA1c between models without and with the potential mediator. RESULTS: Adjusted for age, only a few factors (e.g., pulse, triglycerides, albumin excretion rate) explained more than 10% of the effect of glycemia on CVD risk when considered individually. In multivariable models, these traditional risk factors together mediated up to ∼50% of the effect of glycemia on the risk of CVD. However, the association between HbA1c and the risk of CVD remained highly significant even after adjustment for these risk factors. CONCLUSIONS: While HbA1c is associated with many traditional CVD risk factors, its association with these factors alone cannot explain its effects on risk of CVD. Consequently, aggressive management of traditional nonglycemic CVD risk factors, coupled with aggressive glycemic management, is indicated for individuals with type 1 diabetes.
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In 2011, an observational study using data from 3661 patients in the Swedish National Diabetes Register proposed a 5-year CVD risk model for use in patients with T1DM.
“In 2011, an observational study using the data from 3661 patients in the Swedish National Diabetes Register proposed a 5-year CVD risk model for use in patients with T1DM.789”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [789]
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Amor, A. J., Castelblanco, E., Hernández, M., Marga, G., Granado-Casas, M., Blanco, J., Soldevila, B., Esmatjes, E., Conget, I., Alonso, N., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12782634
Amor, A. J., Castelblanco, E., Hernández, M., Marga, G., Granado-Casas, M., Blanco, J., Soldevila, B., Esmatjes, E., Conget, I., Alonso, N., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12782640
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Amor, A. J., Castelblanco, E., Hernández, M., Marga, G., Granado-Casas, M., Blanco, J., Soldevila, B., Esmatjes, E., Conget, I., Alonso, N., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12782631
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- Authors
- Bebu, I., Braffett, B. H., Orchard, T. J., Lorenzi, G. M., Lachin, J. M., & the DCCT/EDIC Research Group
- Affiliations
- George Washington University (US)
- University of Pittsburgh (US)
- University of California San Diego (US)
- Corresponding author
- Bebu, Ionut
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2019-03-20
- Volume
- 42
- Issue
- 7
- Pages
- 1284-1289
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC6609964
- OpenAlex
- W2923244811
- Cited by
- 62
- References
- 44
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 6 · 2023: 8 · 2022: 4 · 2021: 10 · 2020: 21 · 2019: 5
- FWCI
- 8.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U01-DK-094176, U01-DK-094157)
- 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 › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- type 1 diabetes, glycemia, cardiovascular risk, HbA1c, mediation analysis, cardiovascular risk factors, pulses, triglycerides, urinary albumin excretion rate, tight glycemic control, DCCT/EDIC
- MeSH terms
- Coronary Artery Disease, Diabetes Mellitus, Type 1, Follow-Up Studies, Glycated Hemoglobin, Humans, Risk Factors, Mendelian Randomization Analysis
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