Cited by 1,310Nitric Oxide and Endothelin EffectsDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

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Oscillating Glucose Is More Deleterious to Endothelial Function and Oxidative Stress Than Mean Glucose in Normal and Type 2 Diabetic Patients

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Ceriello, Antonio, Esposito, Katherine, Piconi, Ludovica, Ihnat, Michael A., Thorpe, Jessica E., Testa, Roberto, Boemi, Massimo, Giugliano, Dario·2008·Diabetes

DOI 10.2337/db08-0063

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Abstract

OBJECTIVE—To explore the possibility that oscillating glucose may outweigh A1C levels in determining the risk for cardiovascular diabetes complications. RESEARCH DESIGN AND METHODS—A euinsulinemic hyperglycemic clamp at 5, 10, and 15 mmol/l glucose was given in increasing steps as a single “spike” or oscillating between basal and high levels over 24 h in normal subjects and type 2 diabetic patients. Flow-mediated dilatation, a marker of endothelial function, and plasma 3-nitrotyrosine and 24-h urinary excretion rates of free 8-iso PGF2α, two markers of oxidative stress, were measured over 48 h postclamp. RESULTS—Glucose at two different levels (10 and 15 mmol/l) resulted in a concentration-dependent fasting blood glucose–independent induction of both endothelial dysfunction and oxidative stress in both normal and type 2 diabetic patients. Oscillating glucose between 5 and 15 mmol/l every 6 h for 24 h resulted in further significant increases in endothelial dysfunction and oxidative stress compared with either continuous 10 or 15 mmol/l glucose. CONCLUSIONS—These data suggest that oscillating glucose can have more deleterious effects than constant high glucose on endothelial function and oxidative stress, two key players in favoring cardiovascular complications in diabetes. Concomitant vitamin C infusion can reverse this impairment.

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Authors: Ceriello, A., Esposito, K., Piconi, L., Ihnat, M. A., Thorpe, J. E., Testa, R., Boemi, M., & Giugliano, D.
Affiliations: University Hospital Coventry (GB)
University of Campania "Luigi Vanvitelli" (IT)
University of Udine (IT)
University of Oklahoma Health Sciences Center (US)
Istituti di Ricovero e Cura a Carattere Scientifico (IT)
Corresponding author: Ceriello, Antonio
ORCID: Ceriello, Antonio
Esposito, Katherine
Ihnat, Michael A.
Testa, Roberto
Giugliano, Dario
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2008-05-01
Volume: 57
Issue: 5
Pages: 1349-1354
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/db08-0063
OpenAlex: W2142433177
Cited by: 1,310
References: 40
Citations by year: 2026: 80 · 2025: 74 · 2024: 91 · 2023: 87 · 2022: 88 · 2021: 114 · 2020: 97 · 2019: 79 · 2018: 83 · 2017: 69 · 2016: 69 · 2015: 56 · 2014: 69 · 2013: 58 · 2012: 57
FWCI: 31.01
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
INFM-OAR (INFN Catania) (submittedVersion, other-oa)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
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, endothelial dysfunction, oxidative stress, type 2 diabetes, cardiovascular complications, flow-mediated dilation, nitrotyrosine, 8-isoprostane, hyperglycemic clamp, vitamin C, HbA1c
MeSH terms: Blood Glucose, Diabetes Mellitus, Type 2, Endothelium, Vascular, Female, Glycated Hemoglobin, Homeostasis, Humans, Male, Middle Aged, Oscillometry, Reference Values, Somatostatin, Vasodilation, Oxidative Stress

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Oscillating Glucose Is More Deleterious to Endothelial Function and Oxidative Stress Than Mean Glucose in Normal and Type 2 Diabetic Patients

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