Pathogenesis and pathophysiology of the cardiometabolic syndrome

Kirk, Erik P.; Klein, Samuel

doi:10.1111/j.1559-4572.2009.00054.x

Cited by 195Diabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic DiseasesCardiovascular Disease and Adiposity

Pathogenesis and pathophysiology of the cardiometabolic syndrome

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Kirk, Erik P., Klein, Samuel·2009·The Journal of Clinical Hypertension

DOI 10.1111/j.1559-4572.2009.00054.xPMC PMC2859214

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Abstract

The cardiometabolic syndrome represents a cluster of metabolic abnormalities that are risk factors for cardiovascular disease. The mechanism(s) responsible for developing the cardiometabolic syndrome is not known, but it is likely that multi‐organ insulin resistance, which is a common feature of the cardiometabolic syndrome, is involved. Insulin resistance is an important risk factor for type 2 diabetes and can cause vasoconstriction and renal sodium reabsorption, leading to increased blood pressure. Alterations in adipose tissue fatty acid and adipokine metabolism are involved in the pathogenesis of insulin resistance. Excessive rates of fatty acid release into the bloodstream can impair the ability of insulin to stimulate muscle glucose uptake and suppress hepatic glucose production. Noninfectious systemic inflammation associated with adipocyte and adipose tissue macrophage cytokine production can also cause insulin resistance. In addition, increased free fatty acid delivery to the liver can stimulate hepatic very low‐density lipoprotein triglyceride production, leading to dyslipidemia.

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Weight loss is the cornerstone of therapy for people with obesity because it can ameliorate or completely resolve the metabolic risk factors for diabetes, coronary artery disease, and obesity-associated cancers.
“Weight loss is the cornerstone of therapy for people with obesity because it can ameliorate or completely resolve the metabolic risk factors for diabetes, coronary artery disease, and obesity-associated cancers.”
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The Abstract and Summary describe obesity-related metabolic abnormalities and cardiovascular risk, but neither addresses weight loss as therapy. Searches for weight-loss treatment, resolution of risk factors, and obesity-associated cancers found no passage in our copy supporting the attributed claim. (LLM, conf=0.75)
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[30]Seppala-Lindroos A Vehkavaara S Hakkinen A-M Fat Accumulation in the Liver Is Associated with Defects in Insulin Suppression of Glucose Production and Serum Free Fatty Acids Independent of Obesity in Normal Men 10.1210/jc.87.7.3023 J Clin Endocrinol Metab 2002 87 3023 8 12107194 · DOI · Paper page

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Authors: Kirk, E. P., & Klein, S.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Klein, Samuel
ORCID: Klein, Samuel
Venue: The Journal of Clinical Hypertension
Publisher: Wiley
Published: 2009-12
Volume: 11
Issue: 12
Pages: 761-765
ISSN: 1524-6175 (ISSN-L)
1751-7176
DOI: 10.1111/j.1559-4572.2009.00054.x
PMC: PMC2859214
OpenAlex: W1972602644
Cited by: 195
References: 46
Citations by year: 2026: 24 · 2025: 29 · 2024: 19 · 2023: 12 · 2022: 14 · 2021: 25 · 2020: 10 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 6 · 2013: 8 · 2012: 5
FWCI: 0.96
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Clinical Hypertension (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (K01DK078738)
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 › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords: cardiometabolic syndrome, insulin resistance, type 2 diabetes, hypertension, adipose tissue, adipokines, fatty acid metabolism, systemic inflammation, adipose tissue macrophages, hepatic glucose production, muscle glucose uptake, free fatty acids, dyslipidemia, VLDL, cardiovascular risk
MeSH terms: Cardiovascular Diseases, Diabetes Mellitus, Type 2, Fatty Acids, Humans, Hypertension, Insulin Resistance, Obesity, Risk Factors, Vasoconstriction, Prevalence, Muscle, Skeletal, Metabolic Syndrome

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