Glycemic Variation and Cardiovascular Risk in the Veterans Affairs Diabetes Trial

Zhou, Jin J.; Schwenke, Dawn C.; Bahn, Gideon; Reaven, Peter

doi:10.2337/dc18-0548

Cited by 131Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

Glycemic Variation and Cardiovascular Risk in the Veterans Affairs Diabetes Trial

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Zhou, Jin J., Schwenke, Dawn C., Bahn, Gideon, Reaven, Peter·2018·Diabetes Care

DOI 10.2337/dc18-0548PMC PMC6150432

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Abstract

OBJECTIVE: There is uncertainty about the importance of glycemic variability in cardiovascular complications in patients with type 2 diabetes. Using the Veterans Affairs Diabetes Trial (VADT), we investigated the association between variation in fasting glucose and glycated hemoglobin (HbA1c) over time and the incidence of cardiovascular disease (CVD) and assessed whether this is influenced by intensive or standard glycemic control. RESEARCH DESIGN AND METHODS: During the VADT, fasting glucose and HbA1c were measured every 3 months for up to 84 months in 1,791 individuals. Variability measures included coefficient of variation (CV) and average real variability (ARV) for fasting glucose and HbA1c. Overall mean glucose and HbA1c measures as well as their maximum and the most recent measurement were also examined. RESULTS: Variability measures (CV and ARV) of fasting glucose were significantly associated with CVD even after adjusting for other risk factors, including mean fasting glucose. When considering separately groups receiving intensive and standard glycemic control, this relationship was evident in the intensive treatment group but not in the standard group. Additional adjustment for severe hypoglycemic episodes did not alter the relationship between fasting glucose variability and CVD. Interestingly, no HbA1c measures were associated with CVD after adjusting for multiple baseline risk factors. CONCLUSIONS: Our analysis indicates that in the VADT, variability of fasting glucose plays a role in the development of CVD complications beyond the influence of standard fasting glucose measures. The adverse consequences of fasting glucose variability on CVD appear greatest in those receiving intensive glucose control.

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In VADT, CV and ARV of fasting glucose were significantly associated with cardiovascular disease (CV glucose: p=0.003, OR 1.162, 1.054-1.281; ARV glucose: p=0.0006, OR 1.168, 1.069-1.275).
“CV and ARV of FG were significantly associated with CVD: CV glucose: p=0.003, OR 1.162 (1.054–1.281); ARV glucose: p=0.0006, OR 1.168 (1.069–1.275).”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [51]
In a post-hoc analysis of the Veteran Affairs Diabetes Trial, variability of fasting glucose was significantly associated with cardiovascular disease even after adjusting for different risk factors, including mean fasting glucose.
“The results showed a significant association between variability of fasting glucose and cardiovascular disease even after adjusting for different risk factors, including mean fasting glucose.”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [51]
In a post-hoc analysis of the Veteran Affairs Diabetes Trial, the association was not present for HbA1c variability.
“Conversely, the association was not present for HbA1c variability.”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [51]

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Authors: Zhou, J. J., Schwenke, D. C., Bahn, G., & Reaven, P.
Affiliations: University of Arizona (US)
Carl T. Hayden Veterans Affairs Medical Center (US)
Edward Hines, Jr. VA Hospital (US)
Corresponding author: Zhou, Jin J.
ORCID: Zhou, Jin J.
Schwenke, Dawn C.
Reaven, Peter
Venue: Diabetes Care
Publisher: American Diabetes Association
Published: 2018-08-06
Volume: 41
Issue: 10
Pages: 2187-2194
ISSN: 0149-5992 (ISSN-L)
1935-5548
DOI: 10.2337/dc18-0548
PMC: PMC6150432
OpenAlex: W2887193038
Cited by: 131
References: 37
Citations by year: 2026: 4 · 2025: 14 · 2024: 9 · 2023: 24 · 2022: 16 · 2021: 23 · 2020: 24 · 2019: 17
FWCI: 12.73
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.diabetesjournals.org/content/license (vor, 45 d)
Locations: Diabetes Care (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (R01-067690, 5R01-094775, K01-DK-106116)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: glycemic variability, cardiovascular disease, type 2 diabetes, fasting blood glucose, HbA1c, tight glycemic control, coefficient of variation, average real variability, hypoglycemia
MeSH terms: Aged, Blood Glucose, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Fasting, Female, Glycated Hemoglobin, Humans, Male, Middle Aged, Risk Factors, Veterans

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Glycemic Variation and Cardiovascular Risk in the Veterans Affairs Diabetes Trial

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