Cited by 108Diabetes, Cardiovascular Risks, and LipoproteinsDiabetes Treatment and ManagementChronic Kidney Disease and Diabetes

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Cardiovascular and Kidney Outcomes Across the Glycemic Spectrum

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Honigberg, Michael C., Zekavat, Seyedeh M., Pirruccello, James P., Natarajan, Pradeep, Vaduganathan, Muthiah·2021·Journal of the American College of Cardiology

DOI 10.1016/j.jacc.2021.05.004PMC PMC8324525

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Abstract

Background Treatment guidelines for prediabetes primarily focus on glycemic control and lifestyle management. Few evidence-based cardiovascular and kidney risk-reduction strategies are available in this population. Objectives This study sought to characterize cardiovascular and kidney outcomes across the glycemic spectrum. Methods Among participants in the UK Biobank without prevalent type 1 diabetes, cardiovascular disease, or kidney disease, Cox models tested the association of glycemic exposures (type 2 diabetes [T2D], prediabetes, normoglycemia) with outcomes (atherosclerotic cardiovascular disease [ASCVD], chronic kidney disease [CKD], and heart failure), adjusting for demographic, lifestyle, and cardiometabolic risk factors. Results Among 336,709 individuals (mean age: 56.3 years, 55.4% female), 46,911 (13.9%) had prediabetes and 12,717 (3.8%) had T2D. Over median follow-up of 11.1 years, 6,476 (13.8%) individuals with prediabetes developed ≥1 incident outcome, of whom only 802 (12.4%) developed T2D prior to an incident diagnosis. Prediabetes and T2D were independently associated with ASCVD (prediabetes: adjusted HR [aHR]: 1.11; 95% CI: 1.08-1.15; P < 0.001; T2D: aHR: 1.44; 95% CI: 1.37-1.51; P < 0.001), CKD (prediabetes: aHR: 1.08; 95% CI: 1.02-1.14; P < 0.001; T2D: aHR: 1.57; 95% CI: 1.46-1.69; P < 0.001), and heart failure (prediabetes: aHR: 1.07; 95% CI: 1.01-1.14; P = 0.03; T2D: aHR: 1.25; 95% CI: 1.14-1.37; P < 0.001). Compared with hemoglobin A1c (HbA1c) <5.0%, covariate-adjusted risks increased significantly for ASCVD above HbA1c of 5.4%, CKD above HbA1c of 6.2%, and heart failure above HbA1c of 7.0%. Conclusions Prediabetes and T2D were associated with ASCVD, CKD, and heart failure, but a substantial gradient of risk was observed across HbA 1c levels below the threshold for diabetes. These findings highlight the need to design risk-reduction strategies across the glycemic spectrum.

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Authors: Honigberg, M. C., Zekavat, S. M., Pirruccello, J. P., Natarajan, P., & Vaduganathan, M.
Affiliations: Broad Institute (US)
Brigham and Women's Hospital (US)
Corresponding author: Honigberg, Michael C.
ORCID: Honigberg, Michael C.
Zekavat, Seyedeh M.
Pirruccello, James P.
Natarajan, Pradeep
Vaduganathan, Muthiah
Venue: Journal of the American College of Cardiology
Publisher: Elsevier BV
Published: 2021-08
Volume: 78
Issue: 5
Pages: 453-464
ISSN: 0735-1097 (ISSN-L)
DOI: 10.1016/j.jacc.2021.05.004
PMC: PMC8324525
OpenAlex: W3157902107
Cited by: 108
References: 34
Citations by year: 2026: 21 · 2025: 22 · 2024: 22 · 2023: 26 · 2022: 15 · 2021: 2
FWCI: 12.13
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 367 d)
Locations: Journal of the American College of Cardiology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Alexion Pharmaceuticals
National Heart, Lung, and Blood Institute (R01HL142711, R01HL148050, R01HL148565, R01HL151283, T32HL094301-07)
Baxter Healthcare Corporation
Boehringer Ingelheim
Cytokinetics
Amgen
Fondation Leducq (TNE-18CVD04)
Massachusetts General Hospital
Novartis
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Keywords: prediabetes, type 2 diabetes, HbA1c, glycemic control, atherosclerotic cardiovascular disease, chronic kidney disease, heart failure, cardiovascular risk, kidney disease risk, normoglycemia, UK Biobank, incident disease risk, cardiometabolic risk factors, lifestyle intervention, diabetes prevention, risk mitigation strategies
MeSH terms: Aged, Blood Glucose, Cardiovascular Diseases, Female, United Kingdom, Humans, Kidney Diseases, Male, Middle Aged, Prediabetic State, Biological Specimen Banks

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