Oscillating Glucose Is More Deleterious to Endothelial Function and Oxidative Stress Than Mean Glucose in Normal and Type 2 Diabetic Patients
Open accessAbstract
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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Fluctuations in blood glucose levels may contribute more to outcomes than constant high blood glucose concentrations.
“Other studies have demonstrated that fluctuations in blood glucose levels may contribute more to outcomes than constant high blood glucose concentrations.31–35”
From Increased Time in Range and Fewer Missed Bolus Injections After Introduction of a Smart Connected Insulin Pen (2020) · cites this paper as [31]
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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
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2008-05-01
- Volume
- 57
- Issue
- 5
- Pages
- 1349-1354
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- 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 › 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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