Endothelial Dysfunction in Obesity and Insulin Resistance: A Road to Diabetes and Heart Disease
Open accessAbstract
Obesity, insulin resistance, and endothelial dysfunction closely coexist throughout the natural history of type 2 diabetes. They all can be identified not only in people with type 2 diabetes, but also in various groups at risk for the disease, such as individuals with impaired glucose tolerance, family history of type 2 diabetes, hypertension, dyslipidemia, prior gestational diabetes, or polycystic ovary syndrome. Whereas their evident association cannot fully establish a cause‐effect relationship, fascinating mechanisms that bring them closer together than ever before are rapidly emerging. Central or abdominal obesity leads to insulin resistance and endothelial dysfunction through fat‐derived metabolic products, hormones, and cytokines. Insulin resistance leads to endothelial dysfunction through the frequent association with traditional cardiovascular risk factors and through some more direct novel mechanisms. Some specific and shared insulin signaling abnormalities in muscle, fat, and endothelial cells, as well as some new genetic and nontraditional factors, may contribute to this interesting association. Some recent clinical studies demonstrate that nonpharmacological and pharmacological strategies targeting obesity and/or insulin resistance ameliorate endothelial function and low‐grade inflammation. All these findings have added a new dimension to the association of obesity, insulin resistance, and endothelial dysfunction that may become a key target in the prevention of type 2 diabetes and cardiovascular disease.
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Endothelial dysfunction with consequent blunting of physiological vasodilation is implicated in the pathophysiology of obesity-related hypertension.
“endothelial dysfunction 48 with consequent blunting of physiological vasodilation.49”
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- Ishibashi M, Egashira K, Hiasa K, et al. Anti-inflammatory and anti-atherosclerotic effects of pioglitazone. Hypertension. 2002;40:687-93.
- Charles MA, Morange P, Eschwege E, Andre P, Vague P, Juhan-Vague I. Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondia- betic subjects. The BIGPRO1 Study. Diabetes Care. 1998;21: 1967-72.
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- Authors
- Caballero, A. E.
- Affiliations
- Joslin Diabetes Center (US)
- Corresponding author
- Caballero, A. Enrique
- Venue
- Obesity Research
- Publisher
- Wiley
- Published
- 2003-11
- Volume
- 11
- Issue
- 11
- Pages
- 1278-1289
- ISSN
- 1071-7323 (ISSN-L)
- 1550-8528
- OpenAlex
- W2101835986
- Cited by
- 416
- References
- 92
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 16 · 2023: 9 · 2022: 6 · 2021: 19 · 2020: 9 · 2019: 17 · 2018: 10 · 2017: 17 · 2016: 19 · 2015: 23 · 2014: 30 · 2013: 26 · 2012: 19
- FWCI
- 3.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Obesity Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- endothelial dysfunction, obesity, insulin resistance, type 2 diabetes, abdominal obesity, adipokines, cytokines, insulin signaling, low-grade inflammation, cardiovascular risk factors, impaired glucose tolerance, polycystic ovary syndrome, diabetes prevention, cardiovascular disease prevention
- MeSH terms
- Diabetes Mellitus, Type 2, Endothelium, Vascular, Heart Diseases, Humans, Insulin Resistance, Obesity, Weight Loss
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