The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Effects of Acute and Antecedent Hypoglycemia on Endothelial Function and Markers of Atherothrombotic Balance in Healthy Humans
Abstract
The aim of this study was to determine the effects of single and repeated episodes of clamped hypoglycemia on fibrinolytic balance, proinflammatory biomarkers, proatherothrombotic mechanisms, and endothelial function. Twenty healthy individuals (12 male and 8 female) were studied during separate 2-day randomized protocols. Day 1 consisted of either two 2-h hyperinsulinemic (812 ± 50 pmol/L)-euglycemic (5 ± 0.1 mmol/L) or hyperinsulinemic (812 ± 50 pmol/L)-hypoglycemic (2.9 ± 0.1 mmol/L) clamps. Day 2 consisted of a single 2-h hyperinsulinemic-hypoglycemic clamp. Two-dimensional Doppler ultrasound was used to determine brachial arterial endothelial function. Plasminogen activator inhibitor 1, vascular cell adhesion molecule-1, intracellular adhesion molecule-1, E-selectin, P-selectin, TAT (thrombin/antithrombin complex), tumor necrosis factor-α, and interleukin-6 responses were increased (P < 0.05) during single or repeated hypoglycemia compared with euglycemia. Endogenous and exogenous nitric oxide (NO)-mediated vasodilation were both impaired by repeated hypoglycemia. Neuroendocrine and autonomic nervous system (ANS) responses were also blunted by repeated hypoglycemia (P < 0.05). In summary, acute moderate hypoglycemia impairs fibrinolytic balance; increases proinflammatory responses, platelet activation, and coagulation biomarkers; and reduces NO-mediated endothelial function in healthy individuals. Repeated episodes of hypoglycemia further impair vascular function by additionally reducing exogenously NO-mediated endothelial function and increasing coagulation biomarkers. We conclude that despite reduced neuroendocrine and ANS responses, antecedent hypoglycemia results in greater endothelial dysfunction and an increased proatherothrombotic state compared with a single acute episode of hypoglycemia.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Hypoglycemia also increases inflammatory and immune markers and results in a prothrombotic state.”
From Stress, hypoglycemia, and the autonomic nervous system (2022) · cites this paper as Joy et al., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Effects of Intensive Glucose Lowering in Type 2 Diabetes
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802743 · Cited by 7,888
Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802987 · Cited by 7,397
Intensive versus Conventional Glucose Control in Critically Ill Patients
(2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810625 · Cited by 5,119
Glucose control and vascular complications in veterans with type 2 diabetes
Duckworth, W., Abraira, C., Moritz, T., Reda, D., Emanuele, N., Reaven, P. D., Zieve, F. J., Marks, J., Davis, S. N., Hayward, R., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808431 · Cited by 4,762
Self-citationHypoglycemia and outcome in critically ill patients
Egi, M., Bellomo, R., Stachowski, E., French, C. J., Hart, G. K., Taori, G., Hegarty, C., & Bailey, M. (2010) · Mayo Clinic Proceedings · doi:10.4065/mcp.2009.0394 · Cited by 432
Association of Hypoglycemia and Cardiac Ischemia
Desouza, C., Salazar, H., Cheong, B., Murgo, J., & Fonseca, V. (2003) · Diabetes Care · doi:10.2337/diacare.26.5.1485 · Cited by 406
Vascular disease and diabetes: Is hypoglycaemia an aggravating factor?
Wright, R. J., & Frier, B. M. (2008) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.865 · Cited by 336
Amiel, S. A., Tamborlane, W. V., Simonson, D. C., & Sherwin, R. S. (1987) · New England Journal of Medicine · doi:10.1056/nejm198705283162205 · Cited by 309
Proinflammatory cytokines in response to insulin-induced hypoglycemic stress in healthy subjects
Razavi Nematollahi, L., Kitabchi, A. E., Stentz, F. B., Wan, J. Y., Larijani, B. A., Tehrani, M. M., Gozashti, M. H., Omidfar, K., & Taheri, E. (2009) · Metabolism · doi:10.1016/j.metabol.2008.10.018 · Cited by 210
Effects of Acute Insulin-Induced Hypoglycemia on Indices of Inflammation
Wright, R. J., Newby, D. E., Stirling, D., Ludlam, C. A., Macdonald, I. A., & Frier, B. M. (2010) · Diabetes Care · doi:10.2337/dc10-0013 · Cited by 208
Research works printed but not linked: 26
- Dandona, 2010, Proinflammatory and prothrombotic effects of hypoglycemia, Diabetes Care, 33, 1686, 10.2337/dc10-0503 · DOI
- Dandona, 2007, Effect of hyperglycemia and insulin in acute coronary syndromes, Am J Cardiol, 99, 12H, 10.1016/j.amjcard.2007.04.004 · DOI
- Gogitidze Joy, 2010, Effects of acute hypoglycemia on inflammatory and pro-atherothrombotic biomarkers in individuals with type 1 diabetes and healthy individuals, Diabetes Care, 33, 1529, 10.2337/dc09-0354 · DOI · Paper page
- Abumrad, 1981, Use of a heated superficial hand vein as an alternative site for the measurement of amino acid concentrations and for the study of glucose and alanine kinetics in man, Metabolism, 30, 936, 10.1016/0026-0495(81)90074-3 · DOI · Paper page
- DeFronzo, 1979, Glucose clamp technique: a method for quantifying insulin secretion and resistance, Am J Physiol, 237, E214
- Briscoe, 2008, Effects of a selective serotonin reuptake inhibitor, fluoxetine, on counterregulatory responses to hypoglycemia in healthy individuals, Diabetes, 57, 2453, 10.2337/db08-0236 · DOI
- Wide, 1966, Radioimmunoassay of proteins with the uses of sephadex-coupled antibodies, Biochim Biophys Acta, 130, 257, 10.1016/0304-4165(66)90032-8 · DOI · Paper page
- Causon, 1981, Assay of plasma catecholamines by liquid chromatography with electrochemical detection, Anal Biochem, 116, 223, 10.1016/0003-2697(81)90347-X · DOI
- Ho, 1970, Radiochemical assay of long-chain fatty acids using 63Ni as tracer, Anal Biochem, 36, 105, 10.1016/0003-2697(70)90337-4 · DOI · Paper page
- Sigurdardottir, 2014, Systemic treatment and narrowband ultraviolet B differentially affect cardiovascular risk markers in psoriasis, J Am Acad Dermatol, 70, 1067, 10.1016/j.jaad.2013.12.044 · DOI
- Faulx, 2003, Detection of endothelial dysfunction with brachial artery ultrasound scanning, Am Heart J, 145, 943, 10.1016/S0002-8703(03)00097-8 · DOI
- Chaudhuri, 2012, Cardiovascular benefits of exogenous insulin, J Clin Endocrinol Metab, 97, 3079, 10.1210/jc.2012-1112 · DOI
- Dandona, 2009, Acute myocardial infarction, hyperglycemia, and insulin, J Am Coll Cardiol, 53, 1437, 10.1016/j.jacc.2009.01.040 · DOI
- Poredos, 2013, Testing endothelial function and its clinical relevance, J Atheroscler Thromb, 20, 1, 10.5551/jat.14340 · DOI
- Giménez, 2011, Repeated episodes of hypoglycemia as a potential aggravating factor for preclinical atherosclerosis in subjects with type 1 diabetes, Diabetes Care, 34, 198, 10.2337/dc10-1371 · DOI
- Babar, 2011, Impaired endothelial function in preadolescent children with type 1 diabetes, Diabetes Care, 34, 681, 10.2337/dc10-2134 · DOI
- Wang, 2012, Acute exposure to low glucose rapidly induces endothelial dysfunction and mitochondrial oxidative stress: role for AMP kinase, Arterioscler Thromb Vasc Biol, 32, 712, 10.1161/ATVBAHA.111.227389 · DOI
- Sandu, 2000, Diabetes in the Goto-Kakizaki rat is accompanied by impaired insulin-mediated myosin-bound phosphatase activation and vascular smooth muscle cell relaxation, Diabetes, 49, 2178, 10.2337/diabetes.49.12.2178 · DOI
- Cryer, 2013, Hypoglycemia-associated autonomic failure in diabetes, Handb Clin Neurol, 117, 295, 10.1016/B978-0-444-53491-0.00023-7 · DOI
- Rana, 2011, Acute hypoglycemia decreases myocardial blood flow reserve in patients with type 1 diabetes mellitus and in healthy humans, Circulation, 124, 1548, 10.1161/CIRCULATIONAHA.110.992297 · DOI
- Mathew, 2010, Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy subjects, Cardiovasc Diabetol, 9, 9, 10.1186/1475-2840-9-9 · DOI
- Frost, 2004, Epinephrine stimulates IL-6 expression in skeletal muscle and C2C12 myoblasts: role of c-Jun NH2-terminal kinase and histone deacetylase activity, Am J Physiol Endocrinol Metab, 286, E809, 10.1152/ajpendo.00560.2003 · DOI
- Halleux, 1999, Hormonal control of plasminogen activator inhibitor-1 gene expression and production in human adipose tissue: stimulation by glucocorticoids and inhibition by catecholamines, J Clin Endocrinol Metab, 84, 4097
- van der Poll, 1997, Epinephrine exerts anticoagulant effects during human endotoxemia, J Exp Med, 185, 1143, 10.1084/jem.185.6.1143 · DOI
- Farmer, 2000, beta-adrenergic agonists exert their “anti-inflammatory” effects in monocytic cells through the IkappaB/NF-kappaB pathway, Am J Physiol Lung Cell Mol Physiol, 279, L675, 10.1152/ajplung.2000.279.4.L675 · DOI
- Hafezi-Moghadam, 2002, Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase, Nat Med, 8, 473, 10.1038/nm0502-473 · DOI
Cited by
Amiel, S. A., Aschner, P., Childs, B., Cryer, P. E., de Galan, B. E., Frier, B. M., Gonder-Frederick, L., Heller, S. R., Jones, T., Khunti, K., et al. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30315-2 · Cited by 526
Agiostratidou, G., Anhalt, H., Ball, D., Blonde, L., Gourgari, E., Harriman, K. N., Kowalski, A. J., Madden, P., McAuliffe-Fogarty, A. H., McElwee-Malloy, M., et al. (2017) · Diabetes Care · doi:10.2337/dc17-1624 · Cited by 397
Proinflammatory effects of hypoglycemia in humans with or without diabetes
Ratter, J. M., Rooijackers, H. M. M., Tack, C. J., Hijmans, A. G. M., Netea, M. G., de Galan, B. E., & Stienstra, R. (2017) · Diabetes · doi:10.2337/db16-1091 · Cited by 94
Stress, hypoglycemia, and the autonomic nervous system
Haas, A., Borsook, D., Adler, G., & Freeman, R. (2022) · Autonomic Neuroscience · doi:10.1016/j.autneu.2022.102983 · Cited by 30
Baroreflex sensitivity impairment during hypoglycemia: implications for cardiovascular control
Rao, A. D., Bonyhay, I., Dankwa, J., Baimas-George, M., Kneen, L., Ballatori, S., Freeman, R., & Adler, G. K. (2016) · Diabetes · doi:10.2337/db15-0871 · Cited by 25
Metadata
- Authors
- Joy, N. G., Tate, D. B., Younk, L. M., & Davis, S. N.
- Affiliations
- Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2015-02-18
- Volume
- 64
- Issue
- 7
- Pages
- 2571-2580
- ISSN
- 0012-1797
- 1939-327X
- Cited by
- 99
- References
- 12
- Language
- en
- Funders
- Vanderbilt Diabetes Research and Training ((DRTC) NIH/NIDDK)
- National Institutes of Health (P50 HL081009 NIH/NHLBI, PO1 HL056693 NIH/NHLBI, RO1 DK069803 NIH/NIDDK)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Effects of Acute and Antecedent Hypoglycemia on Endothelial Function and Markers of Atherothrombotic Balance in Healthy Humans. https://app.cochat.ai/papers/10.2337/db14-1729
- The paper
- Joy, N. G., Tate, D. B., Younk, L. M., & Davis, S. N. (2015). Effects of Acute and Antecedent Hypoglycemia on Endothelial Function and Markers of Atherothrombotic Balance in Healthy Humans. Diabetes. https://doi.org/10.2337/db14-1729
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.