Relationship of Insulin Resistance to Prevalence and Progression of Coronary Artery Calcification Beyond Metabolic Syndrome Components

Yamazoe, Masahiro; Hisamatsu, Takashi; Miura, Katsuyuki; Kadowaki, Sayaka; Zaid, Maryam; Kadota, Aya; Torii, Shuki; Miyazawa, Itsuko; Fujiyoshi, Akira; Arima, Hisatomi; Sekikawa, Akira; Maegawa, Hiroshi; Horie, Minoru; Ueshima, Hirotsugu

doi:10.1161/atvbaha.116.307612

Cited by 48 publications

(53 citation statements)

References 24 publications

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“…Some arguments claimed that hyperinsulinemia may indicate a primary disruption that drives IR in obesity (Shanik et al, 2008 ), as the blockade of hyperinsulinemia prevents obesity while increasing energy expenditure (Czech, 2017 ). Fasting insulin, not glucose nor HbA1c, is associated with coronary artery calcification and its progression (Yamazoe et al, 2016 ). Although the hypoglycemic effect is not as significant as metformin, DZF improved hyperinsulinemia and general metabolic homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Dai-Zong-Fang, A Traditional Chinese Herbal Formula, Ameliorates Insulin Resistance in db/db Mice

Zhu

Sun

et al. 2018

Front. Physiol.

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Intricate health problems, such as insulin resistance (IR) and its associated diseases, call for multi-targeted therapies with few side effects. Based on traditional Chinese medicine (TCM), Dai-Zong-Fang (DZF) is an herbal formula mainly composed of Rhizoma Coptidis (Huanglian) and Fructus Aurantii Immaturus (Zhishi), of which berberine and naringin are the main constituents. Though DZF has been clinically used for treatment of IR and metabolic syndrome for decades, its mechanism in vivo remains unknown. In the present study, we observed that both DZF and metformin, the first-line drug for type 2 diabetes, ameliorated insulin resistance with significant improvement of oral glucose tolerance test (OGTT) and homeostasis model assessment of IR (HOMA-IR) level in diabetic C57BL/Ksj-Lepr db−/− (db/db) mice. Low-density lipoprotein cholesterol (LDL-C) and fatty acids (FAs) also decreased in the blood. Higher dose of DZF (1 g·kg−1), but not metformin (0.25 g·kg−1), alleviated hepatic steatosis with reduced liver weight and hepatic lipid accumulation and provided protection from hepatic injury with lower alanine aminotransferase and aspartate aminotransferase and increased hepatic superoxide dismutase activity in db/db mice. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed a decrease in FA synthase gene (Fasn) and an increase in FA oxidation gene Ppara expression. Western blot demonstrated that both DZF and metformin activated 5′ AMP-activated protein kinase (AMPK) but inhibited Notch intracellular domain (NICD) and Hairy/enhancer-of-split 1 (Hes1) of Notch signaling pathway in the liver. DZF also dramatically improved the ultrastructure of skeletal muscles, AMPK phosphorylation, and GLUT4 translocation. DZF also promoted FA transport and oxidation with Cd36 and Cpt1b up-regulation in the skeletal muscle. In conclusion, DZF improves insulin sensitivity by reducing hepatic lipids through AMPK activation and Notch signal pathway inhibition and enhancing energy metabolism in the skeletal muscle via AMPK. This study provides insights into the treatment of complex conditions, such as IR, where TCM herbal formulas exert multipronged effects through correlating pathways.

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Section: Discussionmentioning

confidence: 99%

Dai-Zong-Fang, A Traditional Chinese Herbal Formula, Ameliorates Insulin Resistance in db/db Mice

Zhu

Sun

et al. 2018

Front. Physiol.

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“…(151) Increased prevalence and absolute progression of coronary artery calcification has also been demonstrated in the setting of the MetS and augmented cardiometabolic risk. (152-154)…”

Section: Atherosclerotic Disease and Vascular Calcificationmentioning

confidence: 99%

Cardiovascular consequences of metabolic syndrome

Tune

Goodwill

Sassoon

et al. 2017

Translational Research

373

272

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The metabolic syndrome (MetS) is defined as the concurrence of obesity-associated cardiovascular risk factors including abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension. Earlier conceptualizations of the MetS focused on insulin resistance as a core feature, and it is clearly coincident with the above list of features. Each component of the MetS is an independent risk factor for cardiovascular disease and the combination of these risk factors elevates rates and severity of cardiovascular disease, related to a spectrum of cardiovascular conditions including microvascular dysfunction, coronary atherosclerosis and calcification, cardiac dysfunction, myocardial infarction, and heart failure. While advances in understanding the etiology and consequences of this complex disorder have been made, the underlying pathophysiologic mechanisms remain incompletely understood, and it is unclear how these concurrent risk factors conspire to produce the variety of obesity-associated adverse cardiovascular diseases. In this review we highlight current knowledge regarding the pathophysiologic consequences of obesity and the MetS on cardiovascular function and disease, including considerations of potential physiologic and molecular mechanisms that may contribute to these adverse outcomes.

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“…One plausible mechanism for the difference in the prevalence of CAC between the two populations is increased insulin resistance among US-White indicated by higher BMI. Insulin resistance is independently associated with the CAC-prevalence in the US-White29 and the Japanese 30. The US-White are expected to be more insulin resistant because they had significantly higher BMI compared with the Japanese.…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein particles and coronary artery calcium in middle-aged US-White and Japanese men

et al. 2019

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ObjectiveThis cross-sectional study examined whether contrasting distributions of nuclear magnetic resonance (NMR)-measured lipoproteins contribute to differences in the prevalence of subclinical atherosclerosis measured using coronary artery calcium (CAC) between the two groups of middle-aged males: the US-residing Caucasian (US-White) and Japan-residing Japanese (Japanese).MethodsIn a population-based study of 570 randomly selected asymptomatic men aged 40–49 years (270 US-White and 300 Japanese), we examined the relationship between race/ethnicity, NMR-measured lipoproteins and CAC (measured by Electron Beam CT and quantified using the Agatston method) using multivariable robust Poisson regression adjusting for traditional and novel risk factors for coronary heart disease (CHD).ResultsThe US-White compared with the Japanese had significantly different NMR-measured lipoprotein particle distributions. The US-White had a significantly higher prevalence of CAC≥10 (CAC-prevalence) compared with the Japanese adjusting for CHD risk factors (prevalence ratio (PR)=2.10; 95% CI=1.24 to 3.48), and this difference was partially attenuated (~18%) with further adjustment for lipoprotein levels (PR=1.73; 95% CI=1.02 to 3.08). There was no reclassification improvement with further addition of lipoproteins particle concentrations/size to a model that already included traditionally measured lipids (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), cardiovascular risk factors, and inflammatory markers (net reclassification improvement index=−2% to 3%).ConclusionsVariations in the distribution of NMR-measured lipoprotein particles partially accounted for the difference in the CAC-prevalence between middle-aged US-White and Japanese men.

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Relationship of Insulin Resistance to Prevalence and Progression of Coronary Artery Calcification Beyond Metabolic Syndrome Components

Cited by 48 publications

References 24 publications

Dai-Zong-Fang, A Traditional Chinese Herbal Formula, Ameliorates Insulin Resistance in db/db Mice

Dai-Zong-Fang, A Traditional Chinese Herbal Formula, Ameliorates Insulin Resistance in db/db Mice

Cardiovascular consequences of metabolic syndrome

Lipoprotein particles and coronary artery calcium in middle-aged US-White and Japanese men

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